The Next Step: Formulating State Machine Models for Microbes:
by Ross Overbeek
October, 2010

In this document, I plan to go through the following steps:
  1. First, I will go through some examples of conjectures that follow naturally from a minimal study of atomic regulons (sets of genes that are always co-expressed). My goal is to show that a very simple integration of data (relating to operons, subsystems, and expression data) produces truly impressive results. I have recently collected well over a hundred examples of atomic regulons that can be easily used to produce testable conjectures.
  2. Then, I will reflect on why these conjectures are easy to produce.
  3. I will argue that they are just a by-product of a more important issue -- the need to construct state-machine models based on atomic regulons.
  4. Finally, I will describe what I see as the pipeline needed to really exploit atomic regulons.

Some Examples in the Use of Atomic Regulons

An Example Relating to Ubiquinone/Menaquinone Metablism

As my first example of what might be achievable by studying the atomic regulaons, contider Atomic Regulon 14 in our current set for E.coli:

Pegs in Atomic Regulon 14 [ON=888 OFF=6]


Pearson Coefficients:
PEG peg.2858 peg.2859 peg.2860 peg.2861 peg.3759 peg.3760 peg.3761 peg.3762 peg.3763 peg.3764 peg.3765 peg.3769 peg.3770
fig|83333.1.peg.2858 0.793 0.783 0.707 0.436 0.676 0.659 0.610 0.599 0.692 0.565 0.700 0.701
fig|83333.1.peg.2859 0.793 0.861 0.740 0.462 0.743 0.701 0.570 0.667 0.696 0.590 0.736 0.707
fig|83333.1.peg.2860 0.783 0.861 0.850 0.437 0.735 0.668 0.547 0.632 0.683 0.468 0.727 0.714
fig|83333.1.peg.2861 0.707 0.740 0.850 0.505 0.758 0.741 0.665 0.731 0.727 0.484 0.727 0.697
fig|83333.1.peg.3759 0.436 0.462 0.437 0.505 0.721 0.802 0.766 0.531 0.613 0.517 0.634 0.540
fig|83333.1.peg.3760 0.676 0.743 0.735 0.758 0.721 0.899 0.867 0.856 0.857 0.761 0.818 0.813
fig|83333.1.peg.3761 0.659 0.701 0.668 0.741 0.802 0.899 0.852 0.740 0.853 0.690 0.817 0.801
fig|83333.1.peg.3762 0.610 0.570 0.547 0.665 0.766 0.867 0.852 0.816 0.844 0.778 0.717 0.728
fig|83333.1.peg.3763 0.599 0.667 0.632 0.731 0.531 0.856 0.740 0.816 0.800 0.749 0.736 0.731
fig|83333.1.peg.3764 0.692 0.696 0.683 0.727 0.613 0.857 0.853 0.844 0.800 0.769 0.786 0.794
fig|83333.1.peg.3765 0.565 0.590 0.468 0.484 0.517 0.761 0.690 0.778 0.749 0.769 0.573 0.661
fig|83333.1.peg.3769 0.700 0.736 0.727 0.727 0.634 0.818 0.817 0.717 0.736 0.786 0.573 0.891
fig|83333.1.peg.3770 0.701 0.707 0.714 0.697 0.540 0.813 0.801 0.728 0.731 0.794 0.661 0.891

Functions in Escherichia coli K12
PEG Function Subsystems
fig|83333.1.peg.2858 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinol hydroxylase (EC 1.14.13.-) CBSS-87626.3.peg.3639,Ubiquinone_Biosynthesis
fig|83333.1.peg.2859 2-octaprenyl-6-methoxyphenol hydroxylase (EC 1.14.13.-) CBSS-87626.3.peg.3639,Ubiquinone_Biosynthesis
fig|83333.1.peg.2860 Xaa-Pro aminopeptidase (EC 3.4.11.9) CBSS-87626.3.peg.3639
fig|83333.1.peg.2861 FIG037488: Putative conserved exported protein precursor CBSS-87626.3.peg.3639
fig|83333.1.peg.3759 DNA recombination protein RmuC DNA_repair,_bacterial
fig|83333.1.peg.3760 Ubiquinone/menaquinone biosynthesis methyltransferase UbiE (EC 2.1.1.-) Menaquinone_Biosynthesis_via_Futalosine,Menaquinone_and_Phylloquinone_Biosynthesis,Ubiquinone_Biosynthesis
fig|83333.1.peg.3761 Protein YigP (COG3165) clustered with ubiquinone biosynthetic genes Menaquinone_Biosynthesis_via_Futalosine,Ubiquinone_Biosynthesis
fig|83333.1.peg.3762 Ubiquinone biosynthesis monooxygenase UbiB Ubiquinone_Biosynthesis
fig|83333.1.peg.3763 Twin-arginine translocation protein TatA Cluster-based_Subsystem_Grouping_Hypotheticals_-_perhaps_Proteosome_Related,Twin-arginine_translocation_system,YgfZ
fig|83333.1.peg.3764 Twin-arginine translocation protein TatB Twin-arginine_translocation_system
fig|83333.1.peg.3765 Twin-arginine translocation protein TatC Cluster-based_Subsystem_Grouping_Hypotheticals_-_perhaps_Proteosome_Related,Twin-arginine_translocation_system
fig|83333.1.peg.3769 3-polyprenyl-4-hydroxybenzoate carboxy-lyase (EC 4.1.1.-) Menaquinone_Biosynthesis_via_Futalosine,Ubiquinone_Biosynthesis
fig|83333.1.peg.3770 NAD(P)H-flavin reductase (EC 1.5.1.29) (EC 1.16.1.3) Ubiquinone_Biosynthesis

This is a fairly big "atomic regulon", and it may well not really be "atomic". What we see, it seems to me, is two large gene clusters that seem to have very similar expression profiles. One goes from PEG fig|83333.1.peg.2858 to PEG fig|83333.1.peg.2861. The other goes from PEG fig|83333.1.peg.3759 through PEG fig|83333.1.peg.3770.
The first cluster appears to include two genes relating to ubiquinone/menaquinone metabolism, as well as two less characterized genes. The second cluster appears to include four genes relating to ubiquinone/menaquinone metabolism, three genes relating to a twin-arginine translocation system, a DNA repair gene (rmuC) and a hypothetical (fig|83333.1.peg.3761).
There are a number of relevant points that we should ponder:
  1. First, let us note the expression profiles. It appears that each of the clusters was expressed in 888 experiments and not expressed in 6. It would be good to know what those six experiments were, I think.
  2. The fact that significant genes from the same metabolic activity (ubiquinone/menaquinone metabolism) are present in both clusters supports the position that the clusters are actually related.
  3. It needs to be noted that, while the first cluster may be an operon, the second is not. The gene fig|83333.1.peg.3768 is a transcriptional regulator that breaks the cluster into two potential operons (each containing two of the ubiquinone/menaquinone genes).
The obvious conjectures would be as follows: There is a puzzle here relating to electron transport, transportation across a network (of folded proteins?), and structural aspects of DNA.
I think that we need to study the six experiments, focus on the easiest question now, and think of how to gain more data. I am not sure what it would take to implicate the 7 genes of interest (PEGs 2860, 2861, 3759, 3761, 3763, 3764, and 3765) in ubiquinone metabolism and to clarify their role.

An Example of a Hypothetical Protein Implicated in the TCA: E.coli Atomic Regulon 14

Pearson Coefficients:
PEG peg.713 peg.714 peg.715 peg.716 peg.717 peg.718 peg.719
fig|83333.1.peg.713 0.969 0.918 0.872 0.841 0.760 0.747
fig|83333.1.peg.714 0.969 0.951 0.895 0.848 0.801 0.789
fig|83333.1.peg.715 0.918 0.951 0.933 0.902 0.871 0.871
fig|83333.1.peg.716 0.872 0.895 0.933 0.870 0.859 0.851
fig|83333.1.peg.717 0.841 0.848 0.902 0.870 0.909 0.902
fig|83333.1.peg.718 0.760 0.801 0.871 0.859 0.909 0.976
fig|83333.1.peg.719 0.747 0.789 0.871 0.851 0.902 0.976

Functions in Escherichia coli K12
PEG Function Subsystems
fig|83333.1.peg.713 Succinate dehydrogenase cytochrome b-556 subunit Succinate_dehydrogenase
fig|83333.1.peg.714 Succinate dehydrogenase hydrophobic membrane anchor protein Succinate_dehydrogenase
fig|83333.1.peg.715 Succinate dehydrogenase flavoprotein subunit (EC 1.3.99.1) Serine-glyoxylate_cycle,Succinate_dehydrogenase,TCA_Cycle
fig|83333.1.peg.716 Succinate dehydrogenase iron-sulfur protein (EC 1.3.99.1) 5-FCL-like_protein,Serine-glyoxylate_cycle,Succinate_dehydrogenase,TCA_Cycle,YgfZ
fig|83333.1.peg.717 hypothetical protein
fig|83333.1.peg.718 2-oxoglutarate dehydrogenase E1 component (EC 1.2.4.2) Dehydrogenase_complexes,TCA_Cycle
fig|83333.1.peg.719 Dihydrolipoamide succinyltransferase component (E2) of 2-oxoglutarate dehydrogenase complex (EC 2.3.1.61) Dehydrogenase_complexes,Lipoic_acid_metabolism,TCA_Cycle


Let me begin by saying that it is not clear that this is a real gene, although numerous groups have called it. It is very short (86 aa). If it is real, I claim that it is related to the TCA, and probably to the succinate dehydrogenase or the 2-oxoglutarate dehydrogenase. As I understand the situation, the expression data is overwhelming support that the gene is expressed and translated.

The expression data that we have for this atomic regulon suggests that it was ON in approximately 840 experiments and OFF in about 50-60. We can graph the expression levels for genes 716,717,and 718 to see how they relate, and the correspondence looks pretty good to me:

Here, we have sorted the experiments based on the expression levels of 717 (so the lowest values on the X-axis are for experiments in which 717 had the smallest values), and the expression levels for the 3 genes are shown with the Y-axis being the normalized values.

An Example Relating to Heme/Siroheme Biosynthesis: E.coli Atomic Regulon 16 [ON=748 OFF=115]


Here is another somewhat complex atomic regulon. Note:
Pearson Coefficients:
PEG peg.232 peg.3727 peg.3728 peg.3729 peg.3730 peg.3773 peg.3774 peg.3775 peg.3776 peg.3910 peg.3911 peg.3912
fig|83333.1.peg.232 0.595 0.654 0.540 0.596 0.731 0.607 0.510 0.637 0.615 0.640 0.550
fig|83333.1.peg.3727 0.595 0.878 0.742 0.761 0.746 0.717 0.721 0.744 0.759 0.755 0.652
fig|83333.1.peg.3728 0.654 0.878 0.756 0.770 0.823 0.773 0.737 0.752 0.812 0.794 0.686
fig|83333.1.peg.3729 0.540 0.742 0.756 0.786 0.739 0.776 0.762 0.767 0.713 0.784 0.693
fig|83333.1.peg.3730 0.596 0.761 0.770 0.786 0.769 0.761 0.725 0.745 0.738 0.733 0.650
fig|83333.1.peg.3773 0.731 0.746 0.823 0.739 0.769 0.807 0.732 0.826 0.782 0.761 0.670
fig|83333.1.peg.3774 0.607 0.717 0.773 0.776 0.761 0.807 0.839 0.799 0.744 0.810 0.670
fig|83333.1.peg.3775 0.510 0.721 0.737 0.762 0.725 0.732 0.839 0.849 0.696 0.761 0.758
fig|83333.1.peg.3776 0.637 0.744 0.752 0.767 0.745 0.826 0.799 0.849 0.724 0.766 0.768
fig|83333.1.peg.3910 0.615 0.759 0.812 0.713 0.738 0.782 0.744 0.696 0.724 0.868 0.730
fig|83333.1.peg.3911 0.640 0.755 0.794 0.784 0.733 0.761 0.810 0.761 0.766 0.868 0.736
fig|83333.1.peg.3912 0.550 0.652 0.686 0.693 0.650 0.670 0.670 0.758 0.768 0.730 0.736

Functions in Escherichia coli K12 PEG Function Subsystems
fig|83333.1.peg.232 Aminoacyl-histidine dipeptidase (Peptidase D) (EC 3.4.13.3) Recycling_of_Peptidoglycan_Amino_Acids fig|83333.1.peg.3727 Homolog of E. coli HemY protein Experimental_tye,Heme_and_Siroheme_Biosynthesis fig|83333.1.peg.3728 Homolog of E. coli HemX protein Dissimilatory_nitrite_reductase,Heme_and_Siroheme_Biosynthesis fig|83333.1.peg.3729 Uroporphyrinogen-III synthase (EC 4.2.1.75) Experimental_tye,Heme_and_Siroheme_Biosynthesis fig|83333.1.peg.3730 Porphobilinogen deaminase (EC 2.5.1.61) Experimental_tye,Heme_and_Siroheme_Biosynthesis fig|83333.1.peg.3773 Xaa-Pro dipeptidase PepQ (EC 3.4.13.9) fig|83333.1.peg.3774 hypothetical conserved protein COG1739 Experimental_tye fig|83333.1.peg.3775 Potassium uptake protein TrkH Potassium_homeostasis fig|83333.1.peg.3776 Protoporphyrinogen IX oxidase, oxygen-independent, HemG (EC 1.3.-.-) Experimental_tye,Heme_and_Siroheme_Biosynthesis fig|83333.1.peg.3910 Uroporphyrinogen III decarboxylase (EC 4.1.1.37) Experimental_tye,Heme_and_Siroheme_Biosynthesis fig|83333.1.peg.3911 Endonuclease V (EC 3.1.21.7) DNA_repair,_bacterial fig|83333.1.peg.3912 hypothetical protein I believe that development of a coherent story for this regulon will require someone with far more understanding than I of biochemistry and phisiology.

A Membrane-bound Ni,Fe hydrogenase: E.coli Atomic Regulon 19 [ON=206 OFF=695]

Now, let us shift to an atomic regulon that relates to a membrane-bound Ni,Fe-hydrogenase
Pearson Coefficients:
PEG peg.956 peg.957 peg.958 peg.959 peg.960 peg.961 peg.962 peg.963 peg.964 peg.965
fig|83333.1.peg.956 0.946 0.956 0.951 0.934 0.907 0.885 0.850 0.836 0.827
fig|83333.1.peg.957 0.946 0.967 0.969 0.967 0.946 0.898 0.873 0.786 0.866
fig|83333.1.peg.958 0.956 0.967 0.976 0.963 0.945 0.892 0.878 0.823 0.853
fig|83333.1.peg.959 0.951 0.969 0.976 0.977 0.951 0.899 0.874 0.828 0.861
fig|83333.1.peg.960 0.934 0.967 0.963 0.977 0.964 0.896 0.879 0.804 0.864
fig|83333.1.peg.961 0.907 0.946 0.945 0.951 0.964 0.883 0.877 0.791 0.874
fig|83333.1.peg.962 0.885 0.898 0.892 0.899 0.896 0.883 0.953 0.895 0.929
fig|83333.1.peg.963 0.850 0.873 0.878 0.874 0.879 0.877 0.953 0.865 0.914
fig|83333.1.peg.964 0.836 0.786 0.823 0.828 0.804 0.791 0.895 0.865 0.866
fig|83333.1.peg.965 0.827 0.866 0.853 0.861 0.864 0.874 0.929 0.914 0.866

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.956 Uptake hydrogenase small subunit precursor (EC 1.12.99.6) Hydrogenases,Membrane-bound_Ni,_Fe-hydrogenase fig|83333.1.peg.957 Uptake hydrogenase large subunit (EC 1.12.99.6) Hydrogenases,Membrane-bound_Ni,_Fe-hydrogenase fig|83333.1.peg.958 Ni,Fe-hydrogenase I cytochrome b subunit Hydrogenases,Membrane-bound_Ni,_Fe-hydrogenase fig|83333.1.peg.959 Hydrogenase maturation protease (EC 3.4.24.-) Hydrogenases,Membrane-bound_Ni,_Fe-hydrogenase fig|83333.1.peg.960 Hydrogenase maturation factor hoxO Membrane-bound_Ni,_Fe-hydrogenase fig|83333.1.peg.961 Hydrogenase maturation factor hoxQ Membrane-bound_Ni,_Fe-hydrogenase fig|83333.1.peg.962 Cytochrome d ubiquinol oxidase subunit I (EC 1.10.3.-) [email protected]_copy,Terminal_cytochrome_d_ubiquinol_oxidases,Terminal_cytochrome_oxidases fig|83333.1.peg.963 Cytochrome d ubiquinol oxidase subunit II (EC 1.10.3.-) Bacterial_RNA-metabolizing_Zn-dependent_hydrolases,Conserved_gene_cluster_associated_with_Met-tRNA_formyltransferase,[email protected]_copy,Terminal_cytochrome_d_ubiquinol_oxidases,Terminal_cytochrome_oxidases fig|83333.1.peg.964 Putative periplasmic protein fig|83333.1.peg.965 Phosphoanhydride phosphohydrolase (EC 3.1.3.2) (pH 2.5 acid phosphatase) (AP) / 4- phytase (EC 3.1.3.26) Capsular_Polysaccharides_Biosynthesis_and_Assembly
Let me show you the correspondences in expression between the first gene in this long cluster (956) and two of the genes near the end:

I believe that these tables (and the expression correspondences) mean that the roles of the last four genes in the cluster (962-965) must be interpreted within their presence in the cluster. I consider the existing annotations as unreliable suggestions that could be substantially improved.

Guessing the Substrate of a Transport System: Atomic Regulon 72 [ON=790 OFF=59]

We have hundreds of cases in which we have a co-expressed set of genes that make up a transport system. In some cases, other genes are included in the cluser and they offer substantial clues for characterizing the substrate of the mechanism. Consider the following five genes:
Pearson Coefficients:
PEG peg.402 peg.403 peg.404 peg.405 peg.406
fig|83333.1.peg.402 0.720 0.542 0.648 0.487
fig|83333.1.peg.403 0.720 0.906 0.817 0.697
fig|83333.1.peg.404 0.542 0.906 0.824 0.737
fig|83333.1.peg.405 0.648 0.817 0.824 0.886
fig|83333.1.peg.406 0.487 0.697 0.737 0.886

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.402 S-adenosylmethionine:tRNA ribosyltransferase-isomerase (EC 5.-.-.-) Queuosine-Archaeosine_Biosynthesis,tRNA_modification_Bacteria fig|83333.1.peg.403 tRNA-guanine transglycosylase (EC 2.4.2.29) Queuosine-Archaeosine_Biosynthesis,tRNA_modification_Bacteria fig|83333.1.peg.404 Preprotein translocase subunit YajC (TC 3.A.5.1.1) fig|83333.1.peg.405 Protein-export membrane protein SecD (TC 3.A.5.1.1) fig|83333.1.peg.406 Protein-export membrane protein SecF (TC 3.A.5.1.1)

The genes in the cluster are believed to be ON in 790 experiments and OFF in about 60. If I go to Wikipedia, I find
Queuosine is a modified nucleoside that is present in certain tRNAs in
bacteria and eukaryotes.  Originally identified in E. coli,
queuosine was found to occupy the first anticodon position of tRNAs
for histidine, aspartic acid, asparagine and tyrosine.  The first
anticodon position pairs with the third "wobble" position in codons,
and queuosine improves accuracy of translation. Synthesis of
queuosine begins with GTP. In bacteria, two classes of riboswitch are
known to regulate genes that are involved in the synthesis or
transport of pre-queuosine1, a precursor to queuosine: PreQ1-I
riboswitches and PreQ1-II riboswitches.
The transport mechanism seems to be for moving proteins. That would raise the question "What proteins?". The assertion that queusine can be synthesized or made from pre-queuosine (transported) leads me to suggest that we consider the possibility that pre=queuosine is the substrate. I would not do an experiment before consulting someone who knows something about tRNA modification, but I believe that it does illustrate a class of clues quite nicely. I have sent the clue off to a biologist who might be able to predict the substrate much more accurately than I could.

A Hypothetical Connected to a Sulfur Relay Mediation Complex: E.coli Atomic Regulon 96 [ON=517 OFF=199]

Pearson Coefficients:
PEG peg.3277 peg.3278 peg.3279 peg.3280
fig|83333.1.peg.3277 0.762 0.744 0.663
fig|83333.1.peg.3278 0.762 0.916 0.848
fig|83333.1.peg.3279 0.744 0.916 0.910
fig|83333.1.peg.3280 0.663 0.848 0.910

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.3277 tRNA 5-methylaminomethyl-2-thiouridine synthase TusB Glutathione-regulated_potassium-efflux_system_and_associated_functions,mnm5U34_biosynthesis_bacteria,tRNA_modification_Bacteria fig|83333.1.peg.3278 tRNA 5-methylaminomethyl-2-thiouridine synthase TusC CBSS-326442.4.peg.1852,Glutathione-regulated_potassium-efflux_system_and_associated_functions,mnm5U34_biosynthesis_bacteria,tRNA_modification_Bacteria fig|83333.1.peg.3279 tRNA 5-methylaminomethyl-2-thiouridine synthase TusD CBSS-326442.4.peg.1852,Glutathione-regulated_potassium-efflux_system_and_associated_functions,mnm5U34_biosynthesis_bacteria,tRNA_modification_Bacteria fig|83333.1.peg.3280 Putative DNA-binding protein

Here we have three genes that form a complex: TusBCD. Two papers have been written about this complex in the last few years:
Structure. 2006 Feb;14(2):357-66.

Structural basis for sulfur relay to RNA mediated by heterohexameric TusBCD complex

Numata T, Fukai S, Ikeuchi Y, Suzuki T, Nureki O

Abstract

Uridine at wobble position 34 of tRNA(Lys), tRNA(Glu), and tRNA(Gln)
is exclusively modified into 2-thiouridine (s2U), which is crucial for
both precise codon recognition and recognition by the cognate
aminoacyl-tRNA synthetases. Recent Escherichia coli genetic studies
revealed that the products of five novel genes, tusABCDE, function in
the s2U modification. Here, we solved the 2.15 angstroms crystal
structure of the E. coli TusBCD complex, a sulfur transfer mediator,
forming a heterohexamer composed of a dimer of the
heterotrimer. Structure-based sequence alignment suggested two
putative active site Cys residues, Cys79 (in TusC) and Cys78 (in
TusD), which are exposed on the hexameric complex. In vivo mutant
analyses revealed that only Cys78, in the TusD subunit, participates
in sulfur transfer during the s2U modification process. Since the
single Cys acts as a catalytic residue, we proposed that TusBCD
mediates sulfur relay via a putative persulfide state of the TusD
subunit.

and

Mol Cell. 2006 Jan 6;21(1):97-108

Mechanistic insights into sulfur relay by multiple sulfur mediators
involved in thiouridine biosynthesis at tRNA wobble positions.

Ikeuchi Y, Shigi N, Kato J, Nishimura A, Suzuki T.

Abstract

The wobble bases of bacterial tRNAs responsible for NNR codons are
modified to 5-methylaminomethyl-2-thiouridine (mnm5s2U). 2-thio
modification of mnm5s2U is required for accurate decoding and
essential for normal cell growth. We identified five genes yhhP, yheL,
yheM, yheN, and yccK (named tusA, tusB, tusC, tusD, and tusE,
respectively) that are essential for 2-thiouridylation of mnm5s2U by a
systematic genome-wide screen ("ribonucleome analysis"). Efficient
2-thiouridine formation in vitro was reconstituted with recombinant
TusA, a TusBCD complex, TusE, and previously identified IscS and
MnmA. The desulfurase activity of IscS is stimulated by TusA
binding. IscS transfers the persulfide sulfur to TusA. TusE binds
TusBCD complex and stimulates sulfur transfer from TusA to TusD. TusE
also interacts with an MnmA-tRNA complex. This study revealed that
2-thiouridine formation proceeds through a complex sulfur-relay system
composed of multiple sulfur mediators that select and facilitate
specific sulfur flow to 2-thiouridine from various pathways of sulfur
trafficking.


I would like to focus on fig|83333.1.peg.3280, which is currently assigned the function "predicted DNA-binding transcriptional regulator" by some groups and "Putative DNA-binding protein" within the SEED. If one looks at PFAM hits, you would see
YheO-like PAS domain:

This family contains various hypothetical bacterial proteins that are
similar to the E. coli protein YheO. Their function is unknown, but
are likely to be involved in signalling based on the presence of this
PAS domain.
Here is a plot of the expression values for peg.80 versus peg.77, the last gene in the putative operon.

I am not sure if the gene is a regulatory gene, but it is closely related to the TusBCD complex and its role of sulfur to to 2-thiouridine.

A Component of a Complex: E.coli Atomic Regulon 109 [ON=125 OFF=755]


Pearson Coefficients:
PEG peg.279 peg.280 peg.281 peg.282
fig|83333.1.peg.279 0.832 0.714 0.626
fig|83333.1.peg.280 0.832 0.779 0.688
fig|83333.1.peg.281 0.714 0.779 0.768
fig|83333.1.peg.282 0.626 0.688 0.768

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.279 Hypothetical protein YagQ fig|83333.1.peg.280 Periplasmic aromatic aldehyde oxidoreductase, molybdenum binding subunit YagR CBSS-266117.6.peg.2476,Purine_Utilization,Putative_diaminopropionate_ammonia-lyase_cluster fig|83333.1.peg.281 Periplasmic aromatic aldehyde oxidoreductase, FAD binding subunit YagS Purine_Utilization fig|83333.1.peg.282 Periplasmic aromatic aldehyde oxidoreductase, iron-sulfur subunit YagT CBSS-266117.6.peg.2476,Purine_Utilization,Putative_diaminopropionate_ammonia-lyase_cluster

If you search for domains that hit the hypothetical protein (YagQ), you will find several that indicate the following:
xanthine dehydrogenase accessory protein XdhC

Members of this protein family are the accessory protein XdhC for insertion of the 
molybdenum cofactor into the xanthine dehydrogenase large chain, XdhB, in bacteria. 
This protein is not part of the mature xanthine dehydrogenase. 
Xanthine dehydrogenase is an enzyme for purine catabolism, 
from other purines to xanthine to urate to further breakdown products.



So, one would conjecture that this is a complex similar to xdhABCD, and YagQ plays a role analogous to XdhC.

The Glycine Cleavage System in Staph. aureus: Atomic Regulon 32 [ON=276 OFF=550]

The next example is from Staphylococcus aureus. It relates to a cluster that encodes the genes related to a glycine catabolism complex (I believe).

Pearson Coefficients:
PEG peg.323 peg.324 peg.325 peg.326 peg.327
fig|158878.1.peg.323 0.790 0.762 0.690 0.702
fig|158878.1.peg.324 0.790 0.855 0.780 0.791
fig|158878.1.peg.325 0.762 0.855 0.839 0.767
fig|158878.1.peg.326 0.690 0.780 0.839 0.714
fig|158878.1.peg.327 0.702 0.791 0.767 0.714

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.323 Flavin-utilizing monoxygenases (EC 1.14.-.-) fig|158878.1.peg.324 Glycine cleavage system H protein Glycine_and_Serine_Utilization,Glycine_cleavage_system,Photorespiration_(oxidative_C2_cycle) fig|158878.1.peg.325 hypothetical protein fig|158878.1.peg.326 NAD-dependent protein deacetylases, SIR2 family fig|158878.1.peg.327 Lipoate-protein ligase A Dehydrogenase_complexes,Glycine_cleavage_system,Lipoic_acid_metabolism

Here is a description of glycine cleavage H-proteins: This is a family of glycine cleavage H-proteins, part of the glycine cleavage multienzyme complex (GCV) found in bacteria and the mitochondria of eukaryotes. GCV catalyses the catabolism of glycine in eukaryotes. A lipoyl group is attached to a completely conserved lysine residue. The H protein shuttles the methylamine group of glycine from the P protein to the T protein.

TIGR00545:lipoyltransferase and lipoate-protein ligase
One member of this group of proteins is bovine lipoyltransferase, which transfers the lipoyl group from lipoyl-AMP to the specific Lys of lipoate-dependent enzymes. However, it does not first activate lipoic acid with ATP to create lipoyl-AMP and pyrophosphate. Another member of this group, lipoate-protein ligase A from E. coli, catalyzes both the activation and the transfer of lipoate. Homology between the two is full-length, except for the bovine mitochondrial targeting signal, but is strongest toward the N-terminus.


Now let me quote from the abstract of a paper written in 1990:
JOURNAL OF BACTERIOLOGY, Oct. 1990, p. 6142-6144 Vol. 172, No. 10

The lpd Gene Product Functions as the L Protein in the
Escherichia coli Glycine Cleavage Enzyme System

PAULA S. STEIERT, LORRAINE T. STAUFFER, AND GEORGE V. STAUFFER

The enzyme serine hydroxymethyltransferase catalyzes the
conversion of serine to glycine and
5,10-methylenetetrahydrofolate and provides the major source of
one-carbon units. The oxidative cleavage of glycine to form
NH3, C02, and 5,10-methylenetetrahydrofolate provides a secondary
pathway for the biosynthesis of one-carbon units in mammalian and
bacterial systems. The glycine cleavage
(GCV) enzyme system has been described in Peptococcus
glycinophilus and consists of four protein components
designated P1, P2, P3, and P4. A GCV enzyme system that
can be induced by exogenous glycine has also been demonstrated
in Escherichia coli (9) and is located at minute 63 on
the linkage map (2). Although the system has not been well
characterized, at least one protein from E. coli interacts
catalytically with the P1 protein from P. glycinophilus in the
exchange of bicarbonate with 14C-labeled glycine, indicating
that the two systems may be similar (D. K. Ransom and
R. D. Sagers, Abstr. Annu. Meet. Am. Soc. Microbiol.
1974, P266, p. 189).


If one looks closely, it is clear that this is not the normal version of a glysine cleavage system. The normal one is represented in other genes ()

Sveta Gerdes writes in her subsystem on glycine cleavage system:
    "Gene "out of context": 

     In Chlamydia, Chlamidophyla, Streptococci, Bifidobacteria, Mycoplasma,
     Acinetobacter, etc - a very close homolog of  a Glycine cleavage
     system H protein is present, often - in close proximity of
     Lipoate-protein ligase A.  However, other Glycine cleavage
     system subunits are absent, the function of these proteins is
     unknown"


We can pursue this issue by looking at the expression correlations between the four distinct PEGs assigned the function Lipoate-protein ligase A and the two distinct PEGs labeled as Glycine cleavage system H protein. If you do that, you find just weaker correlations (but no anti-correlations). I believe that getting at the truth will require detailed examination of experimental conditions to see which conditions distinguish expression of the genes.



I probably should not have included that example, but I think that it does illustrate the style of reasoning that is required on every one of these atomic regulons. We will need to filter and prioritize them, and each one requires a fair amount of study.


An Example Relating to Motility: Staph. aureus Atomic Regulon 2 [ON=229 OFF=12]


Pearson Coefficients:
PEG peg.122 peg.1381 peg.1382 peg.2890 peg.2891 peg.2892 peg.2893 peg.2894 peg.2895 peg.2896 peg.2897 peg.2898 peg.2899 peg.2900 peg.2904 peg.2905 peg.2906 peg.2907 peg.2908 peg.2909 peg.2910 peg.2911 peg.2912 peg.2913 peg.2914 peg.2915 peg.2916 peg.2917 peg.2919 peg.2920 peg.2921 peg.2922 peg.2923 peg.2924 peg.2925 peg.2926 peg.2927 peg.2928 peg.2929 peg.2930 peg.2931 peg.2932 peg.2933 peg.2934 peg.2935 peg.2939 peg.2940
fig|211586.9.peg.122 0.724 0.646 0.616 0.586 0.640 0.625 0.519 0.637 0.600 0.628 0.636 0.566 0.579 0.577 0.632 0.615 0.529 0.438 0.461 0.505 0.435 0.631 0.598 0.377 0.457 0.473 0.507 0.534 0.686 0.659 0.664 0.599 0.418 0.418 0.432 0.424 0.329 0.357 0.235 0.325 0.376 0.451 0.383 0.402 0.707 0.788
fig|211586.9.peg.1381 0.724 0.778 0.631 0.507 0.536 0.536 0.507 0.698 0.718 0.737 0.637 0.520 0.532 0.413 0.590 0.645 0.501 0.491 0.483 0.273 0.151 0.533 0.615 0.377 0.494 0.371 0.377 0.673 0.740 0.702 0.689 0.633 0.522 0.504 0.430 0.494 0.460 0.424 0.403 0.439 0.513 0.565 0.561 0.531 0.824 0.810
fig|211586.9.peg.1382 0.646 0.778 0.483 0.390 0.472 0.366 0.273 0.409 0.427 0.504 0.375 0.324 0.464 0.403 0.467 0.492 0.388 0.438 0.366 0.301 0.212 0.413 0.324 0.277 0.299 0.296 0.232 0.325 0.409 0.405 0.430 0.290 0.227 0.365 0.319 0.362 0.278 0.210 0.203 0.297 0.257 0.331 0.315 0.329 0.546 0.590
fig|211586.9.peg.2890 0.616 0.631 0.483 0.868 0.835 0.808 0.695 0.795 0.759 0.764 0.759 0.586 0.424 0.674 0.747 0.627 0.640 0.546 0.540 0.588 0.316 0.664 0.704 0.365 0.457 0.504 0.476 0.687 0.709 0.683 0.660 0.553 0.541 0.650 0.601 0.448 0.431 0.361 0.305 0.325 0.538 0.557 0.524 0.483 0.540 0.566
fig|211586.9.peg.2891 0.586 0.507 0.390 0.868 0.895 0.879 0.682 0.725 0.671 0.678 0.760 0.613 0.480 0.823 0.741 0.608 0.680 0.535 0.592 0.641 0.401 0.668 0.699 0.374 0.486 0.498 0.548 0.586 0.659 0.590 0.582 0.511 0.581 0.661 0.659 0.511 0.400 0.366 0.271 0.322 0.586 0.568 0.542 0.533 0.486 0.526
fig|211586.9.peg.2892 0.640 0.536 0.472 0.835 0.895 0.885 0.736 0.747 0.669 0.715 0.767 0.674 0.578 0.795 0.782 0.682 0.734 0.677 0.669 0.725 0.535 0.792 0.719 0.456 0.516 0.592 0.631 0.563 0.610 0.601 0.609 0.476 0.553 0.683 0.707 0.593 0.481 0.401 0.309 0.345 0.572 0.563 0.506 0.529 0.503 0.555
fig|211586.9.peg.2893 0.625 0.536 0.366 0.808 0.879 0.885 0.819 0.798 0.665 0.698 0.817 0.749 0.592 0.749 0.765 0.731 0.792 0.573 0.664 0.656 0.575 0.773 0.784 0.510 0.598 0.633 0.680 0.592 0.751 0.647 0.614 0.612 0.697 0.691 0.722 0.604 0.494 0.541 0.415 0.445 0.682 0.692 0.623 0.636 0.515 0.577
fig|211586.9.peg.2894 0.519 0.507 0.273 0.695 0.682 0.736 0.819 0.856 0.776 0.792 0.842 0.814 0.595 0.505 0.663 0.755 0.804 0.689 0.716 0.545 0.543 0.835 0.874 0.610 0.620 0.676 0.698 0.761 0.778 0.789 0.752 0.694 0.753 0.717 0.761 0.636 0.672 0.713 0.611 0.548 0.720 0.736 0.650 0.659 0.576 0.604
fig|211586.9.peg.2895 0.637 0.698 0.409 0.795 0.725 0.747 0.798 0.856 0.908 0.897 0.865 0.744 0.529 0.509 0.675 0.703 0.705 0.606 0.582 0.448 0.327 0.769 0.862 0.500 0.583 0.568 0.598 0.823 0.869 0.846 0.790 0.739 0.726 0.667 0.641 0.539 0.566 0.577 0.518 0.466 0.668 0.711 0.653 0.612 0.702 0.716
fig|211586.9.peg.2896 0.600 0.718 0.427 0.759 0.671 0.669 0.665 0.776 0.908 0.946 0.814 0.668 0.468 0.470 0.612 0.619 0.609 0.586 0.519 0.376 0.216 0.696 0.808 0.387 0.536 0.498 0.483 0.843 0.786 0.793 0.769 0.657 0.642 0.681 0.611 0.495 0.550 0.518 0.532 0.431 0.603 0.629 0.602 0.555 0.719 0.711
fig|211586.9.peg.2897 0.628 0.737 0.504 0.764 0.678 0.715 0.698 0.792 0.897 0.946 0.820 0.705 0.577 0.537 0.612 0.635 0.668 0.633 0.591 0.429 0.306 0.754 0.833 0.461 0.588 0.567 0.558 0.803 0.790 0.766 0.766 0.645 0.643 0.708 0.669 0.538 0.563 0.580 0.547 0.471 0.593 0.641 0.607 0.605 0.731 0.744
fig|211586.9.peg.2898 0.636 0.637 0.375 0.759 0.760 0.767 0.817 0.842 0.865 0.814 0.820 0.846 0.684 0.615 0.807 0.817 0.818 0.734 0.745 0.624 0.452 0.809 0.896 0.631 0.724 0.697 0.743 0.821 0.827 0.807 0.779 0.720 0.790 0.765 0.760 0.763 0.718 0.693 0.597 0.614 0.771 0.791 0.746 0.709 0.690 0.717
fig|211586.9.peg.2899 0.566 0.520 0.324 0.586 0.613 0.674 0.749 0.814 0.744 0.668 0.705 0.846 0.814 0.510 0.702 0.802 0.855 0.786 0.857 0.622 0.624 0.869 0.866 0.825 0.848 0.846 0.895 0.677 0.741 0.713 0.699 0.600 0.761 0.756 0.814 0.804 0.765 0.806 0.744 0.799 0.722 0.806 0.714 0.777 0.613 0.678
fig|211586.9.peg.2900 0.579 0.532 0.464 0.424 0.480 0.578 0.592 0.595 0.529 0.468 0.577 0.684 0.814 0.529 0.613 0.727 0.714 0.695 0.803 0.606 0.654 0.773 0.708 0.785 0.837 0.753 0.832 0.472 0.589 0.513 0.535 0.439 0.594 0.630 0.701 0.820 0.626 0.729 0.648 0.744 0.545 0.659 0.596 0.698 0.575 0.661
fig|211586.9.peg.2904 0.577 0.413 0.403 0.674 0.823 0.795 0.749 0.505 0.509 0.470 0.537 0.615 0.510 0.529 0.681 0.545 0.658 0.531 0.559 0.719 0.466 0.609 0.567 0.318 0.436 0.491 0.534 0.381 0.469 0.402 0.447 0.338 0.404 0.597 0.625 0.495 0.320 0.314 0.200 0.275 0.472 0.465 0.429 0.475 0.392 0.456
fig|211586.9.peg.2905 0.632 0.590 0.467 0.747 0.741 0.782 0.765 0.663 0.675 0.612 0.612 0.807 0.702 0.613 0.681 0.856 0.771 0.707 0.683 0.733 0.521 0.706 0.715 0.559 0.578 0.678 0.641 0.618 0.639 0.635 0.590 0.518 0.591 0.656 0.668 0.687 0.627 0.525 0.417 0.518 0.640 0.663 0.602 0.541 0.525 0.579
fig|211586.9.peg.2906 0.615 0.645 0.492 0.627 0.608 0.682 0.731 0.755 0.703 0.619 0.635 0.817 0.802 0.727 0.545 0.856 0.806 0.745 0.752 0.649 0.571 0.755 0.765 0.693 0.690 0.708 0.709 0.665 0.722 0.705 0.659 0.598 0.720 0.706 0.700 0.767 0.747 0.693 0.595 0.680 0.716 0.767 0.686 0.671 0.615 0.670
fig|211586.9.peg.2907 0.529 0.501 0.388 0.640 0.680 0.734 0.792 0.804 0.705 0.609 0.668 0.818 0.855 0.714 0.658 0.771 0.806 0.825 0.815 0.714 0.663 0.839 0.802 0.706 0.692 0.796 0.771 0.606 0.662 0.647 0.645 0.528 0.679 0.765 0.842 0.731 0.718 0.737 0.614 0.642 0.721 0.757 0.655 0.702 0.542 0.595
fig|211586.9.peg.2908 0.438 0.491 0.438 0.546 0.535 0.677 0.573 0.689 0.606 0.586 0.633 0.734 0.786 0.695 0.531 0.707 0.745 0.825 0.816 0.675 0.526 0.794 0.710 0.694 0.647 0.754 0.733 0.580 0.482 0.587 0.613 0.386 0.518 0.709 0.776 0.758 0.753 0.633 0.621 0.623 0.606 0.652 0.587 0.616 0.485 0.523
fig|211586.9.peg.2909 0.461 0.483 0.366 0.540 0.592 0.669 0.664 0.716 0.582 0.519 0.591 0.745 0.857 0.803 0.559 0.683 0.752 0.815 0.816 0.648 0.558 0.796 0.768 0.833 0.832 0.776 0.872 0.626 0.636 0.658 0.684 0.548 0.752 0.806 0.869 0.867 0.797 0.775 0.689 0.770 0.779 0.813 0.742 0.831 0.592 0.633
fig|211586.9.peg.2910 0.505 0.273 0.301 0.588 0.641 0.725 0.656 0.545 0.448 0.376 0.429 0.624 0.622 0.606 0.719 0.733 0.649 0.714 0.675 0.648 0.722 0.718 0.575 0.527 0.467 0.659 0.645 0.369 0.405 0.435 0.446 0.275 0.357 0.542 0.658 0.594 0.484 0.395 0.254 0.366 0.395 0.409 0.328 0.379 0.326 0.423
fig|211586.9.peg.2911 0.435 0.151 0.212 0.316 0.401 0.535 0.575 0.543 0.327 0.216 0.306 0.452 0.624 0.654 0.466 0.521 0.571 0.663 0.526 0.558 0.722 0.709 0.486 0.594 0.469 0.700 0.635 0.157 0.306 0.264 0.263 0.156 0.311 0.401 0.609 0.525 0.435 0.507 0.360 0.421 0.290 0.343 0.209 0.319 0.193 0.334
fig|211586.9.peg.2912 0.631 0.533 0.413 0.664 0.668 0.792 0.773 0.835 0.769 0.696 0.754 0.809 0.869 0.773 0.609 0.706 0.755 0.839 0.794 0.796 0.718 0.709 0.875 0.711 0.700 0.807 0.817 0.632 0.668 0.694 0.691 0.510 0.618 0.710 0.816 0.719 0.669 0.678 0.591 0.580 0.604 0.661 0.558 0.621 0.583 0.652
fig|211586.9.peg.2913 0.598 0.615 0.324 0.704 0.699 0.719 0.784 0.874 0.862 0.808 0.833 0.896 0.866 0.708 0.567 0.715 0.765 0.802 0.710 0.768 0.575 0.486 0.875 0.696 0.744 0.748 0.791 0.794 0.821 0.794 0.758 0.699 0.768 0.749 0.796 0.734 0.725 0.763 0.682 0.629 0.754 0.796 0.734 0.722 0.675 0.694
fig|211586.9.peg.2914 0.377 0.377 0.277 0.365 0.374 0.456 0.510 0.610 0.500 0.387 0.461 0.631 0.825 0.785 0.318 0.559 0.693 0.706 0.694 0.833 0.527 0.594 0.711 0.696 0.849 0.842 0.873 0.532 0.556 0.563 0.567 0.456 0.656 0.656 0.754 0.808 0.815 0.816 0.741 0.858 0.645 0.724 0.608 0.672 0.471 0.534
fig|211586.9.peg.2915 0.457 0.494 0.299 0.457 0.486 0.516 0.598 0.620 0.583 0.536 0.588 0.724 0.848 0.837 0.436 0.578 0.690 0.692 0.647 0.832 0.467 0.469 0.700 0.744 0.849 0.780 0.867 0.634 0.686 0.604 0.616 0.567 0.795 0.782 0.774 0.861 0.771 0.843 0.814 0.889 0.744 0.821 0.785 0.853 0.618 0.647
fig|211586.9.peg.2916 0.473 0.371 0.296 0.504 0.498 0.592 0.633 0.676 0.568 0.498 0.567 0.697 0.846 0.753 0.491 0.678 0.708 0.796 0.754 0.776 0.659 0.700 0.807 0.748 0.842 0.780 0.878 0.537 0.546 0.540 0.526 0.408 0.566 0.690 0.804 0.745 0.752 0.776 0.730 0.742 0.596 0.691 0.590 0.620 0.418 0.493
fig|211586.9.peg.2917 0.507 0.377 0.232 0.476 0.548 0.631 0.680 0.698 0.598 0.483 0.558 0.743 0.895 0.832 0.534 0.641 0.709 0.771 0.733 0.872 0.645 0.635 0.817 0.791 0.873 0.867 0.878 0.572 0.629 0.599 0.607 0.524 0.694 0.717 0.818 0.814 0.733 0.788 0.685 0.765 0.678 0.743 0.657 0.728 0.511 0.579
fig|211586.9.peg.2919 0.534 0.673 0.325 0.687 0.586 0.563 0.592 0.761 0.823 0.843 0.803 0.821 0.677 0.472 0.381 0.618 0.665 0.606 0.580 0.626 0.369 0.157 0.632 0.794 0.532 0.634 0.537 0.572 0.869 0.904 0.872 0.811 0.786 0.726 0.639 0.599 0.707 0.650 0.615 0.572 0.744 0.748 0.733 0.671 0.758 0.723
fig|211586.9.peg.2920 0.686 0.740 0.409 0.709 0.659 0.610 0.751 0.778 0.869 0.786 0.790 0.827 0.741 0.589 0.469 0.639 0.722 0.662 0.482 0.636 0.405 0.306 0.668 0.821 0.556 0.686 0.546 0.629 0.869 0.908 0.858 0.908 0.839 0.659 0.616 0.582 0.580 0.658 0.555 0.582 0.736 0.793 0.760 0.742 0.824 0.821
fig|211586.9.peg.2921 0.659 0.702 0.405 0.683 0.590 0.601 0.647 0.789 0.846 0.793 0.766 0.807 0.713 0.513 0.402 0.635 0.705 0.647 0.587 0.658 0.435 0.264 0.694 0.794 0.563 0.604 0.540 0.599 0.904 0.908 0.964 0.895 0.756 0.613 0.585 0.570 0.642 0.600 0.522 0.535 0.684 0.726 0.671 0.653 0.841 0.827
fig|211586.9.peg.2922 0.664 0.689 0.430 0.660 0.582 0.609 0.614 0.752 0.790 0.769 0.766 0.779 0.699 0.535 0.447 0.590 0.659 0.645 0.613 0.684 0.446 0.263 0.691 0.758 0.567 0.616 0.526 0.607 0.872 0.858 0.964 0.862 0.715 0.637 0.608 0.569 0.642 0.583 0.500 0.531 0.651 0.686 0.623 0.654 0.874 0.856
fig|211586.9.peg.2923 0.599 0.633 0.290 0.553 0.511 0.476 0.612 0.694 0.739 0.657 0.645 0.720 0.600 0.439 0.338 0.518 0.598 0.528 0.386 0.548 0.275 0.156 0.510 0.699 0.456 0.567 0.408 0.524 0.811 0.908 0.895 0.862 0.796 0.511 0.464 0.495 0.519 0.567 0.453 0.472 0.695 0.718 0.692 0.661 0.815 0.770
fig|211586.9.peg.2924 0.418 0.522 0.227 0.541 0.581 0.553 0.697 0.753 0.726 0.642 0.643 0.790 0.761 0.594 0.404 0.591 0.720 0.679 0.518 0.752 0.357 0.311 0.618 0.768 0.656 0.795 0.566 0.694 0.786 0.839 0.756 0.715 0.796 0.796 0.716 0.752 0.742 0.796 0.714 0.743 0.914 0.905 0.878 0.876 0.659 0.650
fig|211586.9.peg.2925 0.418 0.504 0.365 0.650 0.661 0.683 0.691 0.717 0.667 0.681 0.708 0.765 0.756 0.630 0.597 0.656 0.706 0.765 0.709 0.806 0.542 0.401 0.710 0.749 0.656 0.782 0.690 0.717 0.726 0.659 0.613 0.637 0.511 0.796 0.897 0.775 0.812 0.772 0.747 0.729 0.847 0.832 0.802 0.819 0.548 0.566
fig|211586.9.peg.2926 0.432 0.430 0.319 0.601 0.659 0.707 0.722 0.761 0.641 0.611 0.669 0.760 0.814 0.701 0.625 0.668 0.700 0.842 0.776 0.869 0.658 0.609 0.816 0.796 0.754 0.774 0.804 0.818 0.639 0.616 0.585 0.608 0.464 0.716 0.897 0.818 0.813 0.808 0.711 0.701 0.790 0.784 0.705 0.751 0.496 0.542
fig|211586.9.peg.2927 0.424 0.494 0.362 0.448 0.511 0.593 0.604 0.636 0.539 0.495 0.538 0.763 0.804 0.820 0.495 0.687 0.767 0.731 0.758 0.867 0.594 0.525 0.719 0.734 0.808 0.861 0.745 0.814 0.599 0.582 0.570 0.569 0.495 0.752 0.775 0.818 0.852 0.804 0.749 0.817 0.786 0.800 0.756 0.785 0.552 0.586
fig|211586.9.peg.2928 0.329 0.460 0.278 0.431 0.400 0.481 0.494 0.672 0.566 0.550 0.563 0.718 0.765 0.626 0.320 0.627 0.747 0.718 0.753 0.797 0.484 0.435 0.669 0.725 0.815 0.771 0.752 0.733 0.707 0.580 0.642 0.642 0.519 0.742 0.812 0.813 0.852 0.862 0.823 0.831 0.809 0.806 0.733 0.724 0.543 0.545
fig|211586.9.peg.2929 0.357 0.424 0.210 0.361 0.366 0.401 0.541 0.713 0.577 0.518 0.580 0.693 0.806 0.729 0.314 0.525 0.693 0.737 0.633 0.775 0.395 0.507 0.678 0.763 0.816 0.843 0.776 0.788 0.650 0.658 0.600 0.583 0.567 0.796 0.772 0.808 0.804 0.862 0.892 0.857 0.799 0.851 0.781 0.800 0.538 0.566
fig|211586.9.peg.2930 0.235 0.403 0.203 0.305 0.271 0.309 0.415 0.611 0.518 0.532 0.547 0.597 0.744 0.648 0.200 0.417 0.595 0.614 0.621 0.689 0.254 0.360 0.591 0.682 0.741 0.814 0.730 0.685 0.615 0.555 0.522 0.500 0.453 0.714 0.747 0.711 0.749 0.823 0.892 0.879 0.732 0.814 0.786 0.791 0.465 0.469
fig|211586.9.peg.2931 0.325 0.439 0.297 0.325 0.322 0.345 0.445 0.548 0.466 0.431 0.471 0.614 0.799 0.744 0.275 0.518 0.680 0.642 0.623 0.770 0.366 0.421 0.580 0.629 0.858 0.889 0.742 0.765 0.572 0.582 0.535 0.531 0.472 0.743 0.729 0.701 0.817 0.831 0.857 0.879 0.715 0.801 0.758 0.808 0.515 0.548
fig|211586.9.peg.2932 0.376 0.513 0.257 0.538 0.586 0.572 0.682 0.720 0.668 0.603 0.593 0.771 0.722 0.545 0.472 0.640 0.716 0.721 0.606 0.779 0.395 0.290 0.604 0.754 0.645 0.744 0.596 0.678 0.744 0.736 0.684 0.651 0.695 0.914 0.847 0.790 0.786 0.809 0.799 0.732 0.715 0.939 0.912 0.864 0.577 0.558
fig|211586.9.peg.2933 0.451 0.565 0.331 0.557 0.568 0.563 0.692 0.736 0.711 0.629 0.641 0.791 0.806 0.659 0.465 0.663 0.767 0.757 0.652 0.813 0.409 0.343 0.661 0.796 0.724 0.821 0.691 0.743 0.748 0.793 0.726 0.686 0.718 0.905 0.832 0.784 0.800 0.806 0.851 0.814 0.801 0.939 0.955 0.923 0.632 0.631
fig|211586.9.peg.2934 0.383 0.561 0.315 0.524 0.542 0.506 0.623 0.650 0.653 0.602 0.607 0.746 0.714 0.596 0.429 0.602 0.686 0.655 0.587 0.742 0.328 0.209 0.558 0.734 0.608 0.785 0.590 0.657 0.733 0.760 0.671 0.623 0.692 0.878 0.802 0.705 0.756 0.733 0.781 0.786 0.758 0.912 0.955 0.935 0.602 0.575
fig|211586.9.peg.2935 0.402 0.531 0.329 0.483 0.533 0.529 0.636 0.659 0.612 0.555 0.605 0.709 0.777 0.698 0.475 0.541 0.671 0.702 0.616 0.831 0.379 0.319 0.621 0.722 0.672 0.853 0.620 0.728 0.671 0.742 0.653 0.654 0.661 0.876 0.819 0.751 0.785 0.724 0.800 0.791 0.808 0.864 0.923 0.935 0.643 0.636
fig|211586.9.peg.2939 0.707 0.824 0.546 0.540 0.486 0.503 0.515 0.576 0.702 0.719 0.731 0.690 0.613 0.575 0.392 0.525 0.615 0.542 0.485 0.592 0.326 0.193 0.583 0.675 0.471 0.618 0.418 0.511 0.758 0.824 0.841 0.874 0.815 0.659 0.548 0.496 0.552 0.543 0.538 0.465 0.515 0.577 0.632 0.602 0.643 0.958
fig|211586.9.peg.2940 0.788 0.810 0.590 0.566 0.526 0.555 0.577 0.604 0.716 0.711 0.744 0.717 0.678 0.661 0.456 0.579 0.670 0.595 0.523 0.633 0.423 0.334 0.652 0.694 0.534 0.647 0.493 0.579 0.723 0.821 0.827 0.856 0.770 0.650 0.566 0.542 0.586 0.545 0.566 0.469 0.548 0.558 0.631 0.575 0.636 0.958

Functions in Shewanella oneidensis MR-1 PEG Function Subsystems fig|211586.9.peg.122 Flagellar biosynthesis protein FliL Flagellum fig|211586.9.peg.1381 Flagellar motor rotation protein MotA Flagellum fig|211586.9.peg.1382 Flagellar motor rotation protein MotB CBSS-323098.3.peg.2823,Flagellum fig|211586.9.peg.2890 CheW domain protein fig|211586.9.peg.2891 ParA family protein fig|211586.9.peg.2892 hypothetical protein fig|211586.9.peg.2893 Chemotaxis response regulator protein-glutamate methylesterase CheB (EC 3.1.1.61) fig|211586.9.peg.2894 Signal transduction histidine kinase CheA (EC 2.7.3.-) fig|211586.9.peg.2895 Chemotaxis response - phosphatase CheZ fig|211586.9.peg.2896 Chemotaxis regulator - transmits chemoreceptor signals to flagelllar motor components CheY fig|211586.9.peg.2897 RNA polymerase sigma factor for flagellar operon Flagellum,Transcription_initiation,_bacterial_sigma_factors fig|211586.9.peg.2898 Flagellar synthesis regulator FleN Flagellum fig|211586.9.peg.2899 Flagellar biosynthesis protein FlhF Flagellum fig|211586.9.peg.2900 Flagellar biosynthesis protein FlhA Flagellum fig|211586.9.peg.2904 Flagellar biosynthesis protein FliP Flagellum fig|211586.9.peg.2905 Flagellar biosynthesis protein FliO Flagellum fig|211586.9.peg.2906 Flagellar motor switch protein FliN Flagellum fig|211586.9.peg.2907 Flagellar motor switch protein FliM Flagellum fig|211586.9.peg.2908 Flagellar biosynthesis protein FliL Flagellum fig|211586.9.peg.2909 Flagellar hook-length control protein FliK Flagellum fig|211586.9.peg.2910 Flagellar protein FliJ Flagellum fig|211586.9.peg.2911 Flagellum-specific ATP synthase FliI Flagellum fig|211586.9.peg.2912 Flagellar assembly protein fliH fig|211586.9.peg.2913 Flagellar motor switch protein fliG fig|211586.9.peg.2914 Flagellar M-ring protein FliF Flagellum fig|211586.9.peg.2915 Flagellar hook-basal body complex protein fliE fig|211586.9.peg.2916 Flagellar regulatory protein FleQ Flagellum fig|211586.9.peg.2917 Flagellar sensor histidine kinase FleS Flagellum fig|211586.9.peg.2919 Flagellar biosynthesis protein FliS Flagellum fig|211586.9.peg.2920 hypothetical protein fig|211586.9.peg.2921 Flagellar hook-associated protein FliD Flagellum fig|211586.9.peg.2922 Flagellin protein FlaG Flagellum fig|211586.9.peg.2923 Flagellin protein FlaA Flagellum fig|211586.9.peg.2924 Flagellin protein FlaA Flagellum fig|211586.9.peg.2925 Flagellar hook-associated protein FlgL Flagellum fig|211586.9.peg.2926 Flagellar hook-associated protein FlgK Flagellum fig|211586.9.peg.2927 Flagellar protein FlgJ [peptidoglycan hydrolase] (EC 3.2.1.-) Flagellum fig|211586.9.peg.2928 Flagellar P-ring protein FlgI Flagellum fig|211586.9.peg.2929 Flagellar L-ring protein FlgH Flagellum fig|211586.9.peg.2930 Flagellar basal-body rod protein FlgG Flagellum fig|211586.9.peg.2931 Flagellar basal-body rod protein FlgF Flagellum fig|211586.9.peg.2932 Flagellar hook protein FlgE Flagellum fig|211586.9.peg.2933 Flagellar basal-body rod modification protein FlgD Flagellum fig|211586.9.peg.2934 Flagellar basal-body rod protein flgC fig|211586.9.peg.2935 Flagellar basal-body rod protein flgB fig|211586.9.peg.2939 Negative regulator of flagellin synthesis FlgM Flagellum fig|211586.9.peg.2940 Flagellar biosynthesis protein FlgN Flagellum

Look at PEG 2892. It is clearly related to flagellar motility. However, it is worth reflecting that PEG 2891 is also in the same huge group and is now annotated as a ParA family protein (which is a protein that is often described as relating to chromosome partitioning. When that annotation is made precise, it will probably reflect a role in flagellar motility, as well.



Here is an example from Thermus thermophilus HB8:


Pegs in Atomic Regulon 4 [ON=76 OFF=37]


Pearson Coefficients:
PEG peg.776 peg.777 peg.2037 peg.2038 peg.2039 peg.2040 peg.2041 peg.2042 peg.2043 peg.2044 peg.2045 peg.2046 peg.2047 peg.2048 peg.2049
fig|300852.3.peg.776 0.940 0.721 0.845 0.882 0.863 0.808 0.814 0.878 0.849 0.765 0.824 0.800 0.824 0.712
fig|300852.3.peg.777 0.940 0.629 0.821 0.860 0.845 0.843 0.860 0.861 0.854 0.827 0.869 0.865 0.882 0.821
fig|300852.3.peg.2037 0.721 0.629 0.886 0.851 0.898 0.813 0.734 0.845 0.791 0.666 0.663 0.716 0.690 0.584
fig|300852.3.peg.2038 0.845 0.821 0.886 0.962 0.963 0.940 0.924 0.945 0.939 0.873 0.890 0.864 0.875 0.829
fig|300852.3.peg.2039 0.882 0.860 0.851 0.962 0.969 0.951 0.926 0.968 0.961 0.908 0.920 0.901 0.907 0.842
fig|300852.3.peg.2040 0.863 0.845 0.898 0.963 0.969 0.955 0.914 0.976 0.958 0.887 0.877 0.895 0.889 0.823
fig|300852.3.peg.2041 0.808 0.843 0.813 0.940 0.951 0.955 0.965 0.943 0.948 0.916 0.908 0.941 0.908 0.897
fig|300852.3.peg.2042 0.814 0.860 0.734 0.924 0.926 0.914 0.965 0.913 0.930 0.899 0.924 0.929 0.918 0.924
fig|300852.3.peg.2043 0.878 0.861 0.845 0.945 0.968 0.976 0.943 0.913 0.977 0.916 0.902 0.904 0.906 0.839
fig|300852.3.peg.2044 0.849 0.854 0.791 0.939 0.961 0.958 0.948 0.930 0.977 0.954 0.936 0.915 0.928 0.888
fig|300852.3.peg.2045 0.765 0.827 0.666 0.873 0.908 0.887 0.916 0.899 0.916 0.954 0.948 0.906 0.922 0.925
fig|300852.3.peg.2046 0.824 0.869 0.663 0.890 0.920 0.877 0.908 0.924 0.902 0.936 0.948 0.908 0.960 0.938
fig|300852.3.peg.2047 0.800 0.865 0.716 0.864 0.901 0.895 0.941 0.929 0.904 0.915 0.906 0.908 0.946 0.929
fig|300852.3.peg.2048 0.824 0.882 0.690 0.875 0.907 0.889 0.908 0.918 0.906 0.928 0.922 0.960 0.946 0.954
fig|300852.3.peg.2049 0.712 0.821 0.584 0.829 0.842 0.823 0.897 0.924 0.839 0.888 0.925 0.938 0.929 0.954

Functions in Thermus thermophilus HB8 PEG Function Subsystems fig|300852.3.peg.776 Vitamin B12 ABC transporter, B12-binding component BtuF Coenzyme_B12_biosynthesis fig|300852.3.peg.777 Iron(III) dicitrate transport system permease protein FecD (TC 3.A.1.14.1) Flavohaemoglobin fig|300852.3.peg.2037 HoxN/HupN/NixA family cobalt transporter Coenzyme_B12_biosynthesis,Transport_of_Nickel_and_Cobalt fig|300852.3.peg.2038 Cobalt-precorrin-6 synthase, anaerobic Cobalamin_synthesis,Coenzyme_B12_biosynthesis fig|300852.3.peg.2039 Cobalt-precorrin-8x methylmutase (EC 5.4.1.2) Cobalamin_synthesis,Coenzyme_B12_biosynthesis fig|300852.3.peg.2040 Cobalt-precorrin-6y C5-methyltransferase (EC 2.1.1.-) / Cobalt-precorrin-6y C15-methyltransferase [decarboxylating] (EC 2.1.1.-) Coenzyme_B12_biosynthesis fig|300852.3.peg.2041 Cobalt-precorrin-2 C20-methyltransferase (EC 2.1.1.130) Cobalamin_synthesis,Coenzyme_B12_biosynthesis fig|300852.3.peg.2042 Cobalt-precorrin-4 C11-methyltransferase (EC 2.1.1.133) Cobalamin_synthesis,Coenzyme_B12_biosynthesis fig|300852.3.peg.2043 Cobalt-precorrin-3b C17-methyltransferase Cobalamin_synthesis,Coenzyme_B12_biosynthesis fig|300852.3.peg.2044 Cobalamin biosynthesis protein CbiG Cobalamin_synthesis,Coenzyme_B12_biosynthesis fig|300852.3.peg.2045 Sirohydrochlorin cobaltochelatase (EC 4.99.1.3) Coenzyme_B12_biosynthesis,Heme_and_Siroheme_Biosynthesis fig|300852.3.peg.2046 hypothetical protein fig|300852.3.peg.2047 Uroporphyrinogen-III methyltransferase (EC 2.1.1.107) Coenzyme_B12_biosynthesis,Dissimilatory_nitrite_reductase,Heme_and_Siroheme_Biosynthesis,Synechocystis_experimental fig|300852.3.peg.2048 Cobalamin biosynthesis protein BluB @ 5,6-dimethylbenzimidazole synthase, flavin destructase family Cobalamin_synthesis,Coenzyme_B12_biosynthesis fig|300852.3.peg.2049 Adenosylcobinamide-phosphate synthase Cobalamin_synthesis,Coenzyme_B12_biosynthesis,YgfZ

Here we are looking at two clusters of genes. Let me direct your attention to peg.2046 which is currently uncharacterized. I would suggest from the table above that it probably plays a role in Coenzyme B12 biosynthesis.

Here is another one that seems clear to me:

Pegs in Atomic Regulon 6 [ON=65 OFF=48]


Pearson Coefficients:
PEG peg.2131 peg.2134 peg.2135 peg.2136 peg.2137 peg.2138 peg.2139 peg.2146 peg.2147 peg.2148 peg.2149 peg.2150 peg.2151 peg.2152
fig|300852.3.peg.2131 0.778 0.701 0.752 0.771 0.823 0.850 0.446 0.667 0.517 0.546 0.628 0.555 0.538
fig|300852.3.peg.2134 0.778 0.957 0.972 0.955 0.960 0.945 0.734 0.893 0.806 0.816 0.845 0.797 0.792
fig|300852.3.peg.2135 0.701 0.957 0.967 0.939 0.913 0.882 0.774 0.909 0.846 0.875 0.871 0.835 0.847
fig|300852.3.peg.2136 0.752 0.972 0.967 0.954 0.948 0.934 0.733 0.879 0.802 0.818 0.842 0.791 0.795
fig|300852.3.peg.2137 0.771 0.955 0.939 0.954 0.958 0.927 0.648 0.879 0.805 0.802 0.821 0.788 0.768
fig|300852.3.peg.2138 0.823 0.960 0.913 0.948 0.958 0.975 0.608 0.844 0.744 0.744 0.787 0.764 0.737
fig|300852.3.peg.2139 0.850 0.945 0.882 0.934 0.927 0.975 0.575 0.807 0.682 0.685 0.729 0.693 0.674
fig|300852.3.peg.2146 0.446 0.734 0.774 0.733 0.648 0.608 0.575 0.829 0.832 0.847 0.820 0.767 0.824
fig|300852.3.peg.2147 0.667 0.893 0.909 0.879 0.879 0.844 0.807 0.829 0.952 0.960 0.955 0.941 0.945
fig|300852.3.peg.2148 0.517 0.806 0.846 0.802 0.805 0.744 0.682 0.832 0.952 0.953 0.923 0.945 0.941
fig|300852.3.peg.2149 0.546 0.816 0.875 0.818 0.802 0.744 0.685 0.847 0.960 0.953 0.971 0.953 0.974
fig|300852.3.peg.2150 0.628 0.845 0.871 0.842 0.821 0.787 0.729 0.820 0.955 0.923 0.971 0.959 0.970
fig|300852.3.peg.2151 0.555 0.797 0.835 0.791 0.788 0.764 0.693 0.767 0.941 0.945 0.953 0.959 0.970
fig|300852.3.peg.2152 0.538 0.792 0.847 0.795 0.768 0.737 0.674 0.824 0.945 0.941 0.974 0.970 0.970

Functions in Thermus thermophilus HB8 PEG Function Subsystems fig|300852.3.peg.2131 CRISPR-associated protein Cas02710 CRISP_Cmr_Cluster fig|300852.3.peg.2134 CRISPR-associated protein, Csm1 family CRISPR-associated_cluster fig|300852.3.peg.2135 CRISPR-associated protein, Csm2 family CRISPR-associated_cluster fig|300852.3.peg.2136 CRISPR-associated RAMP Csm3 CRISPR-associated_cluster fig|300852.3.peg.2137 CRISPR-associated RAMP protein, Csm4 family CRISPR-associated_cluster fig|300852.3.peg.2138 CRISPR-associated protein, Csm5 family CRISPR-associated_cluster fig|300852.3.peg.2139 CRISPR-associated protein Cas02710 CRISP_Cmr_Cluster fig|300852.3.peg.2146 hypothetical protein fig|300852.3.peg.2147 CRISPR-associated RAMP Cmr2 CRISP_Cmr_Cluster fig|300852.3.peg.2148 CRISPR-associated RAMP Cmr3 CRISP_Cmr_Cluster fig|300852.3.peg.2149 CRISPR-associated RAMP Cmr1 CRISP_Cmr_Cluster fig|300852.3.peg.2150 CRISPR-associated RAMP Cmr4 CRISP_Cmr_Cluster fig|300852.3.peg.2151 CRISPR-associated RAMP Cmr5 CRISP_Cmr_Cluster fig|300852.3.peg.2152 CRISPR-associated RAMP Cmr6 CRISP_Cmr_Cluster

The hypothetical peg.2146 is not in an operon with the other CRISPR-associated proteins; it is divergent. Without the expression data, it would be hard to be certain. With it, it seems pretty clear (I think!). Note that expression is ON in 65 experiments and OFF in 48.


Well, that illustrates my point that the atomic regulons are obviously a powerful source of conjectures relating to the functions of gene products. I have selected most of my examples from Escherichia coli because I think that it will make it easier for the reader to evaluate their significane; however, it should be emphasized that it is completely straightforward to generate reasonable conjectures for a number of organisms already.

Pegs in Atomic Regulon 2 [ON=139 OFF=711]


Pearson Coefficients:
PEG peg.848 peg.849 peg.859 peg.862 peg.880 peg.885 peg.886 peg.887 peg.888 peg.889 peg.890 peg.891 peg.892 peg.893 peg.894 peg.895 peg.896 peg.897 peg.898 peg.899 peg.900 peg.901 peg.902 peg.903 peg.904 peg.905 peg.906 peg.907 peg.909 peg.910 peg.911 peg.2753
fig|158878.1.peg.848 0.920 0.745 0.793 0.751 0.760 0.723 0.758 0.737 0.719 0.794 0.763 0.783 0.766 0.780 0.790 0.786 0.766 0.723 0.593 0.742 0.761 0.729 0.655 0.639 0.687 0.723 0.712 0.638 0.713 0.711 0.738
fig|158878.1.peg.849 0.920 0.713 0.792 0.787 0.741 0.707 0.738 0.707 0.683 0.798 0.755 0.776 0.748 0.761 0.793 0.780 0.753 0.708 0.538 0.718 0.743 0.709 0.611 0.637 0.667 0.715 0.684 0.628 0.713 0.711 0.739
fig|158878.1.peg.859 0.745 0.713 0.736 0.593 0.714 0.679 0.696 0.667 0.702 0.684 0.690 0.682 0.667 0.681 0.698 0.697 0.693 0.638 0.534 0.652 0.682 0.657 0.591 0.627 0.669 0.689 0.690 0.603 0.713 0.710 0.820
fig|158878.1.peg.862 0.793 0.792 0.736 0.712 0.711 0.684 0.696 0.654 0.675 0.715 0.728 0.695 0.704 0.681 0.721 0.713 0.712 0.626 0.527 0.644 0.693 0.657 0.578 0.590 0.623 0.624 0.656 0.600 0.653 0.666 0.734
fig|158878.1.peg.880 0.751 0.787 0.593 0.712 0.677 0.634 0.662 0.623 0.638 0.640 0.688 0.655 0.673 0.663 0.696 0.668 0.694 0.631 0.542 0.639 0.712 0.651 0.580 0.586 0.636 0.616 0.630 0.611 0.663 0.669 0.625
fig|158878.1.peg.885 0.760 0.741 0.714 0.711 0.677 0.909 0.854 0.813 0.820 0.805 0.862 0.837 0.835 0.851 0.829 0.846 0.865 0.807 0.689 0.812 0.852 0.818 0.744 0.751 0.708 0.734 0.785 0.767 0.784 0.783 0.691
fig|158878.1.peg.886 0.723 0.707 0.679 0.684 0.634 0.909 0.883 0.848 0.780 0.802 0.877 0.821 0.836 0.864 0.786 0.832 0.874 0.833 0.774 0.815 0.868 0.826 0.812 0.825 0.763 0.721 0.764 0.831 0.776 0.790 0.655
fig|158878.1.peg.887 0.758 0.738 0.696 0.696 0.662 0.854 0.883 0.918 0.851 0.826 0.897 0.862 0.894 0.915 0.848 0.911 0.895 0.926 0.837 0.906 0.938 0.929 0.893 0.840 0.844 0.811 0.828 0.889 0.863 0.864 0.727
fig|158878.1.peg.888 0.737 0.707 0.667 0.654 0.623 0.813 0.848 0.918 0.824 0.842 0.867 0.857 0.866 0.918 0.830 0.892 0.874 0.928 0.865 0.909 0.909 0.923 0.913 0.836 0.834 0.856 0.834 0.863 0.832 0.830 0.707
fig|158878.1.peg.889 0.719 0.683 0.702 0.675 0.638 0.820 0.780 0.851 0.824 0.822 0.847 0.808 0.845 0.824 0.804 0.859 0.846 0.819 0.707 0.829 0.864 0.845 0.751 0.702 0.737 0.743 0.844 0.756 0.774 0.787 0.707
fig|158878.1.peg.890 0.794 0.798 0.684 0.715 0.640 0.805 0.802 0.826 0.842 0.822 0.887 0.883 0.887 0.859 0.847 0.887 0.891 0.843 0.670 0.840 0.831 0.833 0.750 0.768 0.751 0.827 0.861 0.763 0.781 0.783 0.739
fig|158878.1.peg.891 0.763 0.755 0.690 0.728 0.688 0.862 0.877 0.897 0.867 0.847 0.887 0.847 0.901 0.884 0.837 0.902 0.942 0.888 0.806 0.869 0.921 0.875 0.842 0.854 0.829 0.777 0.856 0.876 0.815 0.847 0.709
fig|158878.1.peg.892 0.783 0.776 0.682 0.695 0.655 0.837 0.821 0.862 0.857 0.808 0.883 0.847 0.892 0.909 0.880 0.911 0.874 0.873 0.679 0.872 0.852 0.875 0.768 0.726 0.725 0.848 0.818 0.738 0.819 0.796 0.729
fig|158878.1.peg.893 0.766 0.748 0.667 0.704 0.673 0.835 0.836 0.894 0.866 0.845 0.887 0.901 0.892 0.906 0.869 0.920 0.919 0.901 0.761 0.893 0.902 0.899 0.816 0.787 0.780 0.823 0.863 0.816 0.835 0.830 0.720
fig|158878.1.peg.894 0.780 0.761 0.681 0.681 0.663 0.851 0.864 0.915 0.918 0.824 0.859 0.884 0.909 0.906 0.861 0.922 0.908 0.932 0.808 0.919 0.912 0.916 0.870 0.807 0.808 0.867 0.831 0.825 0.848 0.841 0.731
fig|158878.1.peg.895 0.790 0.793 0.698 0.721 0.696 0.829 0.786 0.848 0.830 0.804 0.847 0.837 0.880 0.869 0.861 0.900 0.856 0.841 0.661 0.840 0.840 0.863 0.739 0.705 0.721 0.819 0.821 0.740 0.814 0.811 0.722
fig|158878.1.peg.896 0.786 0.780 0.697 0.713 0.668 0.846 0.832 0.911 0.892 0.859 0.887 0.902 0.911 0.920 0.922 0.900 0.910 0.915 0.749 0.910 0.915 0.922 0.824 0.779 0.802 0.858 0.866 0.815 0.860 0.848 0.755
fig|158878.1.peg.897 0.766 0.753 0.693 0.712 0.694 0.865 0.874 0.895 0.874 0.846 0.891 0.942 0.874 0.919 0.908 0.856 0.910 0.897 0.804 0.880 0.918 0.885 0.838 0.833 0.806 0.811 0.869 0.848 0.820 0.846 0.708
fig|158878.1.peg.898 0.723 0.708 0.638 0.626 0.631 0.807 0.833 0.926 0.928 0.819 0.843 0.888 0.873 0.901 0.932 0.841 0.915 0.897 0.858 0.925 0.936 0.941 0.918 0.832 0.852 0.853 0.845 0.879 0.862 0.860 0.707
fig|158878.1.peg.899 0.593 0.538 0.534 0.527 0.542 0.689 0.774 0.837 0.865 0.707 0.670 0.806 0.679 0.761 0.808 0.661 0.749 0.804 0.858 0.814 0.877 0.829 0.941 0.838 0.836 0.701 0.735 0.887 0.731 0.770 0.564
fig|158878.1.peg.900 0.742 0.718 0.652 0.644 0.639 0.812 0.815 0.906 0.909 0.829 0.840 0.869 0.872 0.893 0.919 0.840 0.910 0.880 0.925 0.814 0.918 0.919 0.872 0.792 0.810 0.856 0.840 0.828 0.843 0.833 0.722
fig|158878.1.peg.901 0.761 0.743 0.682 0.693 0.712 0.852 0.868 0.938 0.909 0.864 0.831 0.921 0.852 0.902 0.912 0.840 0.915 0.918 0.936 0.877 0.918 0.935 0.906 0.848 0.875 0.811 0.862 0.905 0.864 0.875 0.728
fig|158878.1.peg.902 0.729 0.709 0.657 0.657 0.651 0.818 0.826 0.929 0.923 0.845 0.833 0.875 0.875 0.899 0.916 0.863 0.922 0.885 0.941 0.829 0.919 0.935 0.891 0.808 0.841 0.854 0.857 0.864 0.874 0.861 0.729
fig|158878.1.peg.903 0.655 0.611 0.591 0.578 0.580 0.744 0.812 0.893 0.913 0.751 0.750 0.842 0.768 0.816 0.870 0.739 0.824 0.838 0.918 0.941 0.872 0.906 0.891 0.868 0.866 0.804 0.789 0.908 0.817 0.827 0.645
fig|158878.1.peg.904 0.639 0.637 0.627 0.590 0.586 0.751 0.825 0.840 0.836 0.702 0.768 0.854 0.726 0.787 0.807 0.705 0.779 0.833 0.832 0.838 0.792 0.848 0.808 0.868 0.881 0.788 0.793 0.891 0.840 0.870 0.707
fig|158878.1.peg.905 0.687 0.667 0.669 0.623 0.636 0.708 0.763 0.844 0.834 0.737 0.751 0.829 0.725 0.780 0.808 0.721 0.802 0.806 0.852 0.836 0.810 0.875 0.841 0.866 0.881 0.805 0.785 0.869 0.866 0.882 0.750
fig|158878.1.peg.906 0.723 0.715 0.689 0.624 0.616 0.734 0.721 0.811 0.856 0.743 0.827 0.777 0.848 0.823 0.867 0.819 0.858 0.811 0.853 0.701 0.856 0.811 0.854 0.804 0.788 0.805 0.839 0.738 0.872 0.842 0.776
fig|158878.1.peg.907 0.712 0.684 0.690 0.656 0.630 0.785 0.764 0.828 0.834 0.844 0.861 0.856 0.818 0.863 0.831 0.821 0.866 0.869 0.845 0.735 0.840 0.862 0.857 0.789 0.793 0.785 0.839 0.810 0.832 0.835 0.745
fig|158878.1.peg.909 0.638 0.628 0.603 0.600 0.611 0.767 0.831 0.889 0.863 0.756 0.763 0.876 0.738 0.816 0.825 0.740 0.815 0.848 0.879 0.887 0.828 0.905 0.864 0.908 0.891 0.869 0.738 0.810 0.817 0.839 0.653
fig|158878.1.peg.910 0.713 0.713 0.713 0.653 0.663 0.784 0.776 0.863 0.832 0.774 0.781 0.815 0.819 0.835 0.848 0.814 0.860 0.820 0.862 0.731 0.843 0.864 0.874 0.817 0.840 0.866 0.872 0.832 0.817 0.937 0.823
fig|158878.1.peg.911 0.711 0.711 0.710 0.666 0.669 0.783 0.790 0.864 0.830 0.787 0.783 0.847 0.796 0.830 0.841 0.811 0.848 0.846 0.860 0.770 0.833 0.875 0.861 0.827 0.870 0.882 0.842 0.835 0.839 0.937 0.816
fig|158878.1.peg.2753 0.738 0.739 0.820 0.734 0.625 0.691 0.655 0.727 0.707 0.707 0.739 0.709 0.729 0.720 0.731 0.722 0.755 0.708 0.707 0.564 0.722 0.728 0.729 0.645 0.707 0.750 0.776 0.745 0.653 0.823 0.816

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.848 Excisionase [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.849 Hypothetical protein, SAV0849 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.859 Hypothetical protein, PV83 orf12 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.862 Hypothetical protein, phi-ETA orf16 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.880 Hypothetical protein, SAV0880 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.885 Phage terminase, small subunit Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.886 Phage terminase, large subunit Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.887 Phage portal Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.888 Phage minor head protein Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.889 unknown function fig|158878.1.peg.890 Phage capsid and scaffold Phage_capsid_proteins,Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.891 Phage head protein [SA bacteriophages 11, Mu50B] / Phage major capsid protein #Fam0008 Phage_capsid_proteins,Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.892 Phage major capsid protein #Fam0008 Phage_capsid_proteins,Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.893 Phage transcriptional terminator Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.894 phi 11 orf36 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.895 hypothetical protein fig|158878.1.peg.896 phi 11 orf37 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.897 phi 11 orf38 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.898 Phage tail protein Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.899 phi 11 orf40 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.900 phi 11 orf41 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.901 Tape measure protein [SA bacteriophages 11, Mu50B] Phage_tail_proteins,Phage_tail_proteins_2,Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.902 phi 11 orf43 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.903 Phage minor structural protein Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.904 Putative major teichoic acid biosynthesis protein C Staphylococcal_phi-Mu50B-like_prophages,Teichoic_and_lipoteichoic_acids_biosynthesis fig|158878.1.peg.905 hypothetical protein within a prophage fig|158878.1.peg.906 Hypothetical protein, phi-ETA orf42 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.907 Hypothetical protein, phi-ETA orf58 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.909 Bifunctional autolysin Atl / N-acetylmuramoyl-L-alanine amidase (EC 3.5.1.28) / Endo-beta-N-acetylglucosaminidase (EC 3.2.1.96) Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.910 Tail fiber protein [SA bacteriophages 11, Mu50B] [SS] Phage_tail_fiber_proteins,Phage_tail_proteins,Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.911 Hypothetical protein, phi-ETA orf63 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages fig|158878.1.peg.2753 Phage protein Staphylococcal_phi-Mu50B-like_prophages

The genes encoding peg.890 or peg.895 are clearly implicated in phage-related machinery. The context supplied by the atomic regulon makes this apparent.

Pegs in Atomic Regulon 3 [ON=390 OFF=451]


Pearson Coefficients:
PEG peg.2388 peg.2391 peg.2392 peg.2393 peg.2394 peg.2395 peg.2396 peg.2397 peg.2398 peg.2399 peg.2400 peg.2401
fig|158878.1.peg.2388 0.614 0.461 0.492 0.619 0.737 0.745 0.753 0.799 0.790 0.815 0.759
fig|158878.1.peg.2391 0.614 0.736 0.763 0.713 0.726 0.583 0.477 0.686 0.596 0.602 0.563
fig|158878.1.peg.2392 0.461 0.736 0.918 0.842 0.627 0.588 0.485 0.679 0.599 0.538 0.663
fig|158878.1.peg.2393 0.492 0.763 0.918 0.870 0.572 0.574 0.477 0.691 0.626 0.557 0.637
fig|158878.1.peg.2394 0.619 0.713 0.842 0.870 0.658 0.711 0.638 0.779 0.729 0.654 0.721
fig|158878.1.peg.2395 0.737 0.726 0.627 0.572 0.658 0.841 0.761 0.802 0.749 0.783 0.769
fig|158878.1.peg.2396 0.745 0.583 0.588 0.574 0.711 0.841 0.940 0.852 0.839 0.872 0.847
fig|158878.1.peg.2397 0.753 0.477 0.485 0.477 0.638 0.761 0.940 0.805 0.804 0.879 0.841
fig|158878.1.peg.2398 0.799 0.686 0.679 0.691 0.779 0.802 0.852 0.805 0.899 0.876 0.858
fig|158878.1.peg.2399 0.790 0.596 0.599 0.626 0.729 0.749 0.839 0.804 0.899 0.848 0.840
fig|158878.1.peg.2400 0.815 0.602 0.538 0.557 0.654 0.783 0.872 0.879 0.876 0.848 0.842
fig|158878.1.peg.2401 0.759 0.563 0.663 0.637 0.721 0.769 0.847 0.841 0.858 0.840 0.842

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.2388 Nitrate/nitrite transporter Nitrate_and_nitrite_ammonification fig|158878.1.peg.2391 Two-component response regulator fig|158878.1.peg.2392 Two component sensor histidine kinase fig|158878.1.peg.2393 hypothetical protein fig|158878.1.peg.2394 Respiratory nitrate reductase gamma chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification fig|158878.1.peg.2395 Respiratory nitrate reductase delta chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification fig|158878.1.peg.2396 Respiratory nitrate reductase beta chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification fig|158878.1.peg.2397 Respiratory nitrate reductase alpha chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification fig|158878.1.peg.2398 Uroporphyrinogen-III methyltransferase (EC 2.1.1.107) Coenzyme_B12_biosynthesis,Dissimilatory_nitrite_reductase,Heme_and_Siroheme_Biosynthesis,Synechocystis_experimental fig|158878.1.peg.2399 Nitrite reductase [NAD(P)H] small subunit (EC 1.7.1.4) Nitrate_and_nitrite_ammonification fig|158878.1.peg.2400 Nitrite reductase [NAD(P)H] large subunit (EC 1.7.1.4) Nitrate_and_nitrite_ammonification fig|158878.1.peg.2401 Sirohydrochlorin ferrochelatase (EC 4.99.1.4) Heme_and_Siroheme_Biosynthesis

The connection between peg.2388, peg.2391, peg.2392, peg.2401 and the rest of the cluster appears questionable. In such cases, it is useful to examine the strengths of the Pearson Correlation coefficients (PCs) against all of the other genes in the genome. Here are the relevant summaries:

Connections for fig|158878.1.peg.2388
PC PEG Function Subsystems
0.815 fig|158878.1.peg.2400 Nitrite reductase [NAD(P)H] large subunit (EC 1.7.1.4) Nitrate_and_nitrite_ammonification
0.799 fig|158878.1.peg.2398 Uroporphyrinogen-III methyltransferase (EC 2.1.1.107) Coenzyme_B12_biosynthesis,Dissimilatory_nitrite_reductase,Heme_and_Siroheme_Biosynthesis,Synechocystis_experimental
0.790 fig|158878.1.peg.2399 Nitrite reductase [NAD(P)H] small subunit (EC 1.7.1.4) Nitrate_and_nitrite_ammonification
0.759 fig|158878.1.peg.2401 Sirohydrochlorin ferrochelatase (EC 4.99.1.4) Heme_and_Siroheme_Biosynthesis
0.753 fig|158878.1.peg.2397 Respiratory nitrate reductase alpha chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.745 fig|158878.1.peg.2396 Respiratory nitrate reductase beta chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.737 fig|158878.1.peg.2395 Respiratory nitrate reductase delta chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification


Connections for fig|158878.1.peg.2391
PC PEG Function Subsystems
0.763 fig|158878.1.peg.2393 hypothetical protein
0.736 fig|158878.1.peg.2392 Two component sensor histidine kinase
0.726 fig|158878.1.peg.2395 Respiratory nitrate reductase delta chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.713 fig|158878.1.peg.2394 Respiratory nitrate reductase gamma chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification



Connections for fig|158878.1.peg.2392
PC PEG Function Subsystems
0.918 fig|158878.1.peg.2393 hypothetical protein
0.842 fig|158878.1.peg.2394 Respiratory nitrate reductase gamma chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.784 fig|158878.1.peg.2638 immunodominant antigen B



Connections for fig|158878.1.peg.2393
PC PEG Function Subsystems
0.918 fig|158878.1.peg.2392 Two component sensor histidine kinase
0.870 fig|158878.1.peg.2394 Respiratory nitrate reductase gamma chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.763 fig|158878.1.peg.2391 Two-component response regulator



Connections for fig|158878.1.peg.2401
PC PEG Function Subsystems
0.858 fig|158878.1.peg.2398 Uroporphyrinogen-III methyltransferase (EC 2.1.1.107) Coenzyme_B12_biosynthesis,Dissimilatory_nitrite_reductase,Heme_and_Siroheme_Biosynthesis,Synechocystis_experimental
0.847 fig|158878.1.peg.2396 Respiratory nitrate reductase beta chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.842 fig|158878.1.peg.2400 Nitrite reductase [NAD(P)H] large subunit (EC 1.7.1.4) Nitrate_and_nitrite_ammonification
0.841 fig|158878.1.peg.2397 Respiratory nitrate reductase alpha chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.840 fig|158878.1.peg.2399 Nitrite reductase [NAD(P)H] small subunit (EC 1.7.1.4) Nitrate_and_nitrite_ammonification
0.785 fig|158878.1.peg.305 formate/nitrite transporter family protein
0.769 fig|158878.1.peg.2395 Respiratory nitrate reductase delta chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification
0.759 fig|158878.1.peg.2388 Nitrate/nitrite transporter Nitrate_and_nitrite_ammonification
0.721 fig|158878.1.peg.2394 Respiratory nitrate reductase gamma chain (EC 1.7.99.4) Nitrate_and_nitrite_ammonification


In each case, I have shown just the best hits (i.e., I deleted only weaker hits than those shown). This, in my mind, makes an interesting case that
  1. the two-component regulatory system implemented by peg.2391 and peg.2392 relate to "Nitrate and nitrite ammonification" (I am not even sure what that precisely means, but I think that it is straightforward to study the subsystem and literature to gain a detailed grasp), and
  2. peg.2393 relates to "Nitrate and nitrite ammonification" or to the regulation of that process.


Pegs in Atomic Regulon 12 [ON=97 OFF=751]


This next example appears to quite problematic. It illustrates how a combination of clues can be accumulated, gradually leading to a situation in which meaningful conjectures might be formulated.


Pearson Coefficients:
PEG peg.399 peg.400 peg.401 peg.402 peg.403 peg.404 peg.405 peg.406 peg.407
fig|158878.1.peg.399 0.859 0.841 0.878 0.863 0.829 0.855 0.826 0.820
fig|158878.1.peg.400 0.859 0.913 0.932 0.889 0.821 0.924 0.842 0.901
fig|158878.1.peg.401 0.841 0.913 0.911 0.832 0.787 0.899 0.816 0.870
fig|158878.1.peg.402 0.878 0.932 0.911 0.878 0.827 0.937 0.842 0.903
fig|158878.1.peg.403 0.863 0.889 0.832 0.878 0.838 0.860 0.835 0.872
fig|158878.1.peg.404 0.829 0.821 0.787 0.827 0.838 0.831 0.868 0.808
fig|158878.1.peg.405 0.855 0.924 0.899 0.937 0.860 0.831 0.838 0.894
fig|158878.1.peg.406 0.826 0.842 0.816 0.842 0.835 0.868 0.838 0.825
fig|158878.1.peg.407 0.820 0.901 0.870 0.903 0.872 0.808 0.894 0.825

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.399 hypothetical protein fig|158878.1.peg.400 lipoprotein, NLP/P60 family fig|158878.1.peg.401 hypothetical protein fig|158878.1.peg.402 hypothetical protein fig|158878.1.peg.403 hypothetical protein fig|158878.1.peg.404 hypothetical protein fig|158878.1.peg.405 hypothetical protein fig|158878.1.peg.406 hypothetical protein fig|158878.1.peg.407 FIG086557: Conjugation related protein


First, it is worth noting that very similar clusters of genes exist in Listeria monocytogenes EGD-e, Enterococcus faecalis V583, Enterococcus faecalis plasmid pCF10, Clostridium difficile, Streptococcus pneumoniae, and Streptococcus agalactiae. It is the result of a plasmid conjugation event (I think).

A few related facts support this hypothesis:
Taken together these paint an obvious picture, I think.

Now, if we look at the precise PC connections for some of the genes, we see

Connections for fig|158878.1.peg.400
PC PEG Function Subsystems
0.932 fig|158878.1.peg.402 hypothetical protein
0.925 fig|158878.1.peg.408 hypothetical protein
0.925 fig|158878.1.peg.409 hypothetical protein
0.924 fig|158878.1.peg.411 hypothetical protein
0.924 fig|158878.1.peg.405 hypothetical protein
0.913 fig|158878.1.peg.401 hypothetical protein
0.905 fig|158878.1.peg.415 Transposase
0.902 fig|158878.1.peg.412 hypothetical protein
0.901 fig|158878.1.peg.407 FIG086557: Conjugation related protein
0.898 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.889 fig|158878.1.peg.403 hypothetical protein
0.885 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.884 fig|158878.1.peg.410 hypothetical protein
0.869 fig|158878.1.peg.865 HNH homing endonuclease
0.859 fig|158878.1.peg.399 hypothetical protein
0.858 fig|158878.1.peg.394 hhypothetical protein
0.853 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.851 fig|158878.1.peg.868 Phage replication initiation
0.843 fig|158878.1.peg.397 hypothetical protein
0.842 fig|158878.1.peg.406 hypothetical protein
0.841 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.829 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.829 fig|158878.1.peg.392 Integrase
0.823 fig|158878.1.peg.395 hypothetical protein
0.823 fig|158878.1.peg.916 hypothetical protein
0.821 fig|158878.1.peg.404 hypothetical protein
0.820 fig|158878.1.peg.858 unknown function
0.818 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.796 fig|158878.1.peg.854 unknown function
0.787 fig|158878.1.peg.2021 Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.786 fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.774 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.765 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.757 fig|158878.1.peg.2020 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.752 fig|158878.1.peg.1999 hypothetical protein
0.751 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.750 fig|158878.1.peg.47 Disulfide bond regulator Disulphide_related_cluster
0.750 fig|158878.1.peg.884 Integrase regulator RinA Staphylococcal_phi-Mu50B-like_prophages
0.746 fig|158878.1.peg.872 Hypothetical protein, PV83 orf22 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.739 fig|158878.1.peg.2023 Hypothetical SAV0789 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.737 fig|158878.1.peg.72 Potassium-transporting ATPase A chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
0.726 fig|158878.1.peg.32 hypothetical protein
0.720 fig|158878.1.peg.76 hypothetical protein
0.718 fig|158878.1.peg.34 Bleomycin resistance protein
0.715 fig|158878.1.peg.71 Osmosensitive K+ channel histidine kinase KdpD (EC 2.7.3.-) Potassium_homeostasis
0.708 fig|158878.1.peg.802 Pathogenicity island SaPIn1
0.707 fig|158878.1.peg.49 FIG003846: hypothetical protein Disulphide_related_cluster
0.703 fig|158878.1.peg.69 Conserved hypothetical protein
0.701 fig|158878.1.peg.2022 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI



Connections for fig|158878.1.peg.401
PC PEG Function Subsystems
0.913 fig|158878.1.peg.409 hypothetical protein
0.913 fig|158878.1.peg.400 lipoprotein, NLP/P60 family
0.911 fig|158878.1.peg.402 hypothetical protein
0.904 fig|158878.1.peg.411 hypothetical protein
0.900 fig|158878.1.peg.412 hypothetical protein
0.899 fig|158878.1.peg.405 hypothetical protein
0.892 fig|158878.1.peg.408 hypothetical protein
0.890 fig|158878.1.peg.415 Transposase
0.870 fig|158878.1.peg.407 FIG086557: Conjugation related protein
0.860 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.847 fig|158878.1.peg.394 hhypothetical protein
0.844 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.841 fig|158878.1.peg.399 hypothetical protein
0.839 fig|158878.1.peg.410 hypothetical protein
0.832 fig|158878.1.peg.403 hypothetical protein
0.821 fig|158878.1.peg.392 Integrase
0.820 fig|158878.1.peg.865 HNH homing endonuclease
0.820 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.816 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.816 fig|158878.1.peg.406 hypothetical protein
0.815 fig|158878.1.peg.397 hypothetical protein
0.805 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.803 fig|158878.1.peg.868 Phage replication initiation
0.787 fig|158878.1.peg.404 hypothetical protein
0.783 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.782 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.778 fig|158878.1.peg.395 hypothetical protein
0.768 fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.761 fig|158878.1.peg.916 hypothetical protein
0.747 fig|158878.1.peg.2021 Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.742 fig|158878.1.peg.858 unknown function
0.728 fig|158878.1.peg.2020 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.723 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.721 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.720 fig|158878.1.peg.884 Integrase regulator RinA Staphylococcal_phi-Mu50B-like_prophages
0.711 fig|158878.1.peg.47 Disulfide bond regulator Disulphide_related_cluster
0.709 fig|158878.1.peg.872 Hypothetical protein, PV83 orf22 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.706 fig|158878.1.peg.72 Potassium-transporting ATPase A chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis



Connections for fig|158878.1.peg.402
PC PEG Function Subsystems
0.937 fig|158878.1.peg.405 hypothetical protein
0.932 fig|158878.1.peg.400 lipoprotein, NLP/P60 family
0.925 fig|158878.1.peg.411 hypothetical protein
0.924 fig|158878.1.peg.408 hypothetical protein
0.914 fig|158878.1.peg.409 hypothetical protein
0.911 fig|158878.1.peg.401 hypothetical protein
0.905 fig|158878.1.peg.415 Transposase
0.903 fig|158878.1.peg.412 hypothetical protein
0.903 fig|158878.1.peg.407 FIG086557: Conjugation related protein
0.895 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.878 fig|158878.1.peg.410 hypothetical protein
0.878 fig|158878.1.peg.403 hypothetical protein
0.878 fig|158878.1.peg.399 hypothetical protein
0.878 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.869 fig|158878.1.peg.394 hhypothetical protein
0.851 fig|158878.1.peg.868 Phage replication initiation
0.849 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.849 fig|158878.1.peg.865 HNH homing endonuclease
0.849 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.842 fig|158878.1.peg.406 hypothetical protein
0.840 fig|158878.1.peg.397 hypothetical protein
0.832 fig|158878.1.peg.392 Integrase
0.829 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.827 fig|158878.1.peg.404 hypothetical protein
0.824 fig|158878.1.peg.395 hypothetical protein
0.813 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.811 fig|158878.1.peg.858 unknown function
0.788 fig|158878.1.peg.2021 Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.787 fig|158878.1.peg.916 hypothetical protein
0.770 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.769 fig|158878.1.peg.854 unknown function
0.765 fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.761 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.748 fig|158878.1.peg.47 Disulfide bond regulator Disulphide_related_cluster
0.748 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.744 fig|158878.1.peg.2020 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.737 fig|158878.1.peg.1999 hypothetical protein
0.735 fig|158878.1.peg.72 Potassium-transporting ATPase A chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
0.733 fig|158878.1.peg.884 Integrase regulator RinA Staphylococcal_phi-Mu50B-like_prophages
0.724 fig|158878.1.peg.872 Hypothetical protein, PV83 orf22 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.724 fig|158878.1.peg.32 hypothetical protein
0.722 fig|158878.1.peg.71 Osmosensitive K+ channel histidine kinase KdpD (EC 2.7.3.-) Potassium_homeostasis
0.709 fig|158878.1.peg.34 Bleomycin resistance protein
0.706 fig|158878.1.peg.76 hypothetical protein
0.704 fig|158878.1.peg.2023 Hypothetical SAV0789 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.700 fig|158878.1.peg.69 Conserved hypothetical protein



Connections for fig|158878.1.peg.403
PC PEG Function Subsystems
0.904 fig|158878.1.peg.410 hypothetical protein
0.902 fig|158878.1.peg.408 hypothetical protein
0.889 fig|158878.1.peg.400 lipoprotein, NLP/P60 family
0.884 fig|158878.1.peg.858 unknown function
0.878 fig|158878.1.peg.402 hypothetical protein
0.872 fig|158878.1.peg.407 FIG086557: Conjugation related protein
0.870 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.863 fig|158878.1.peg.399 hypothetical protein
0.860 fig|158878.1.peg.405 hypothetical protein
0.858 fig|158878.1.peg.411 hypothetical protein
0.857 fig|158878.1.peg.865 HNH homing endonuclease
0.851 fig|158878.1.peg.868 Phage replication initiation
0.851 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.846 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.841 fig|158878.1.peg.397 hypothetical protein
0.838 fig|158878.1.peg.404 hypothetical protein
0.836 fig|158878.1.peg.409 hypothetical protein
0.836 fig|158878.1.peg.412 hypothetical protein
0.835 fig|158878.1.peg.406 hypothetical protein
0.832 fig|158878.1.peg.401 hypothetical protein
0.829 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.824 fig|158878.1.peg.854 unknown function
0.822 fig|158878.1.peg.916 hypothetical protein
0.821 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.818 fig|158878.1.peg.395 hypothetical protein
0.811 fig|158878.1.peg.392 Integrase
0.810 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.796 fig|158878.1.peg.415 Transposase
0.787 fig|158878.1.peg.394 hhypothetical protein
0.786 fig|158878.1.peg.2023 Hypothetical SAV0789 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.775 fig|158878.1.peg.1999 hypothetical protein
0.763 fig|158878.1.peg.77 hypothetical protein
0.762 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.761 fig|158878.1.peg.396 hypothetical protein
0.759 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.748 fig|158878.1.peg.49 FIG003846: hypothetical protein Disulphide_related_cluster
0.741 fig|158878.1.peg.72 Potassium-transporting ATPase A chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
0.740 fig|158878.1.peg.34 Bleomycin resistance protein
0.739 fig|158878.1.peg.2020 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.738 fig|158878.1.peg.47 Disulfide bond regulator Disulphide_related_cluster
0.738 fig|158878.1.peg.2021 Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.737 fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.736 fig|158878.1.peg.58 hypothetical protein
0.734 fig|158878.1.peg.46 Zn-dependent hydroxyacylglutathione hydrolase Disulphide_related_cluster
0.734 fig|158878.1.peg.872 Hypothetical protein, PV83 orf22 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.733 fig|158878.1.peg.1078 hypothetical protein
0.733 fig|158878.1.peg.32 hypothetical protein
0.733 fig|158878.1.peg.76 hypothetical protein
0.732 fig|158878.1.peg.69 Conserved hypothetical protein
0.731 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.716 fig|158878.1.peg.884 Integrase regulator RinA Staphylococcal_phi-Mu50B-like_prophages
0.713 fig|158878.1.peg.57 DNA repair protein RadC truncated by transposon Tn554
0.711 fig|158878.1.peg.917 hypothetical protein
0.710 fig|158878.1.peg.45 Polysulfide binding protein Disulphide_related_cluster
0.704 fig|158878.1.peg.64 hypothetical protein



Connections for fig|158878.1.peg.404
PC PEG Function Subsystems
0.884 fig|158878.1.peg.392 Integrase
0.878 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.875 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.868 fig|158878.1.peg.406 hypothetical protein
0.850 fig|158878.1.peg.397 hypothetical protein
0.842 fig|158878.1.peg.410 hypothetical protein
0.838 fig|158878.1.peg.403 hypothetical protein
0.838 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.836 fig|158878.1.peg.408 hypothetical protein
0.831 fig|158878.1.peg.405 hypothetical protein
0.829 fig|158878.1.peg.399 hypothetical protein
0.827 fig|158878.1.peg.402 hypothetical protein
0.823 fig|158878.1.peg.411 hypothetical protein
0.821 fig|158878.1.peg.400 lipoprotein, NLP/P60 family
0.816 fig|158878.1.peg.395 hypothetical protein
0.814 fig|158878.1.peg.412 hypothetical protein
0.808 fig|158878.1.peg.407 FIG086557: Conjugation related protein
0.806 fig|158878.1.peg.415 Transposase
0.802 fig|158878.1.peg.394 hhypothetical protein
0.790 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.789 fig|158878.1.peg.868 Phage replication initiation
0.787 fig|158878.1.peg.401 hypothetical protein
0.787 fig|158878.1.peg.409 hypothetical protein
0.778 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.771 fig|158878.1.peg.858 unknown function
0.759 fig|158878.1.peg.916 hypothetical protein
0.751 fig|158878.1.peg.865 HNH homing endonuclease
0.749 fig|158878.1.peg.393 hypothetical protein
0.744 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.740 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.729 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.724 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.719 fig|158878.1.peg.2023 Hypothetical SAV0789 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.717 fig|158878.1.peg.854 unknown function
0.705 fig|158878.1.peg.396 hypothetical protein



Connections for fig|158878.1.peg.405
PC PEG Function Subsystems
0.937 fig|158878.1.peg.402 hypothetical protein
0.925 fig|158878.1.peg.411 hypothetical protein
0.924 fig|158878.1.peg.400 lipoprotein, NLP/P60 family
0.913 fig|158878.1.peg.409 hypothetical protein
0.910 fig|158878.1.peg.415 Transposase
0.907 fig|158878.1.peg.408 hypothetical protein
0.899 fig|158878.1.peg.401 hypothetical protein
0.897 fig|158878.1.peg.412 hypothetical protein
0.894 fig|158878.1.peg.407 FIG086557: Conjugation related protein
0.889 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.874 fig|158878.1.peg.410 hypothetical protein
0.869 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.862 fig|158878.1.peg.394 hhypothetical protein
0.860 fig|158878.1.peg.403 hypothetical protein
0.855 fig|158878.1.peg.399 hypothetical protein
0.850 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.847 fig|158878.1.peg.865 HNH homing endonuclease
0.838 fig|158878.1.peg.406 hypothetical protein
0.838 fig|158878.1.peg.868 Phage replication initiation
0.837 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.831 fig|158878.1.peg.404 hypothetical protein
0.830 fig|158878.1.peg.392 Integrase
0.830 fig|158878.1.peg.397 hypothetical protein
0.827 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.821 fig|158878.1.peg.395 hypothetical protein
0.794 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.792 fig|158878.1.peg.858 unknown function
0.787 fig|158878.1.peg.2021 Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.780 fig|158878.1.peg.916 hypothetical protein
0.770 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.762 fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.759 fig|158878.1.peg.854 unknown function
0.748 fig|158878.1.peg.2020 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.745 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.736 fig|158878.1.peg.884 Integrase regulator RinA Staphylococcal_phi-Mu50B-like_prophages
0.736 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.731 fig|158878.1.peg.47 Disulfide bond regulator Disulphide_related_cluster
0.720 fig|158878.1.peg.1999 hypothetical protein
0.718 fig|158878.1.peg.72 Potassium-transporting ATPase A chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
0.710 fig|158878.1.peg.872 Hypothetical protein, PV83 orf22 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.701 fig|158878.1.peg.71 Osmosensitive K+ channel histidine kinase KdpD (EC 2.7.3.-) Potassium_homeostasis



Connections for fig|158878.1.peg.406
PC PEG Function Subsystems
0.873 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.868 fig|158878.1.peg.404 hypothetical protein
0.862 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.862 fig|158878.1.peg.392 Integrase
0.861 fig|158878.1.peg.397 hypothetical protein
0.847 fig|158878.1.peg.411 hypothetical protein
0.845 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.842 fig|158878.1.peg.400 lipoprotein, NLP/P60 family
0.842 fig|158878.1.peg.402 hypothetical protein
0.840 fig|158878.1.peg.408 hypothetical protein
0.838 fig|158878.1.peg.405 hypothetical protein
0.835 fig|158878.1.peg.403 hypothetical protein
0.835 fig|158878.1.peg.412 hypothetical protein
0.830 fig|158878.1.peg.410 hypothetical protein
0.826 fig|158878.1.peg.399 hypothetical protein
0.825 fig|158878.1.peg.407 FIG086557: Conjugation related protein
0.824 fig|158878.1.peg.415 Transposase
0.816 fig|158878.1.peg.401 hypothetical protein
0.816 fig|158878.1.peg.409 hypothetical protein
0.805 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.800 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.798 fig|158878.1.peg.868 Phage replication initiation
0.795 fig|158878.1.peg.395 hypothetical protein
0.792 fig|158878.1.peg.394 hhypothetical protein
0.787 fig|158878.1.peg.865 HNH homing endonuclease
0.775 fig|158878.1.peg.916 hypothetical protein
0.761 fig|158878.1.peg.858 unknown function
0.760 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.758 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.744 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.738 fig|158878.1.peg.854 unknown function
0.729 fig|158878.1.peg.393 hypothetical protein
0.716 fig|158878.1.peg.872 Hypothetical protein, PV83 orf22 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.714 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.709 fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages



Connections for fig|158878.1.peg.407
PC PEG Function Subsystems
0.903 fig|158878.1.peg.402 hypothetical protein
0.901 fig|158878.1.peg.400 lipoprotein, NLP/P60 family
0.898 fig|158878.1.peg.408 hypothetical protein
0.894 fig|158878.1.peg.405 hypothetical protein
0.876 fig|158878.1.peg.411 hypothetical protein
0.872 fig|158878.1.peg.403 hypothetical protein
0.871 fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
0.870 fig|158878.1.peg.401 hypothetical protein
0.869 fig|158878.1.peg.410 hypothetical protein
0.865 fig|158878.1.peg.409 hypothetical protein
0.850 fig|158878.1.peg.412 hypothetical protein
0.844 fig|158878.1.peg.791 Hypothetical SAV0791 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.843 fig|158878.1.peg.865 HNH homing endonuclease
0.838 fig|158878.1.peg.415 Transposase
0.838 fig|158878.1.peg.868 Phage replication initiation
0.836 fig|158878.1.peg.792 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.825 fig|158878.1.peg.406 hypothetical protein
0.823 fig|158878.1.peg.394 hhypothetical protein
0.820 fig|158878.1.peg.399 hypothetical protein
0.816 fig|158878.1.peg.392 Integrase
0.815 fig|158878.1.peg.1989 hypothetical protein within prophage phiN315
0.814 fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
0.814 fig|158878.1.peg.397 hypothetical protein
0.809 fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
0.808 fig|158878.1.peg.404 hypothetical protein
0.795 fig|158878.1.peg.395 hypothetical protein
0.781 fig|158878.1.peg.858 unknown function
0.781 fig|158878.1.peg.916 hypothetical protein
0.767 fig|158878.1.peg.2021 Putative DNA helicase, superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.764 fig|158878.1.peg.790 Hypothetical SAV0790 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.762 fig|158878.1.peg.854 unknown function
0.759 fig|158878.1.peg.869 DNA replication protein DnaC DNA-replication
0.755 fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages
0.748 fig|158878.1.peg.1999 hypothetical protein
0.734 fig|158878.1.peg.2020 Hypothetical SAV0792 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.731 fig|158878.1.peg.47 Disulfide bond regulator Disulphide_related_cluster
0.721 fig|158878.1.peg.884 Integrase regulator RinA Staphylococcal_phi-Mu50B-like_prophages
0.718 fig|158878.1.peg.72 Potassium-transporting ATPase A chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
0.715 fig|158878.1.peg.912 Phage holin Phage_lysis_modules,Staphylococcal_phi-Mu50B-like_prophages
0.708 fig|158878.1.peg.2023 Hypothetical SAV0789 homolog in superantigen-encoding pathogenicity islands SaPI Staphylococcal_pathogenicity_islands_SaPI
0.705 fig|158878.1.peg.34 Bleomycin resistance protein
0.702 fig|158878.1.peg.71 Osmosensitive K+ channel histidine kinase KdpD (EC 2.7.3.-) Potassium_homeostasis
0.702 fig|158878.1.peg.69 Conserved hypothetical protein




It may appear tedious to go through all of these tables of connections, but there are gems in the details. In any event, our original cluster of hypothetical genes is now (I believe) solidly tied to a number of components of the cellular machinery related to pathogenicity.

Pegs in Atomic Regulon 37 [ON=329 OFF=512]



This atomic regulon represents Fatty Acid Metabolism, with an additional function that converts acetoacetyl-CoA to acetoacetate (see Synthesis and degradation of ketone bodies).
Our actual annotations for this cluster are wrong in two ways:
  1. We have assigned peg.233 the function Glutaryl-CoA dehydrogenase (EC 1.3.99.7). It should probably be Acyl coenzyme A dehydrogenase (EC 1.3.99.13).
  2. peg.235, which is now labeled hypothetical protein, should be 3-oxoacid CoA-transferase (EC 2.8.3.5).
Pearson Coefficients:
PEG peg.231 peg.232 peg.233 peg.234 peg.235
fig|158878.1.peg.231 0.827 0.904 0.867 0.838
fig|158878.1.peg.232 0.827 0.916 0.930 0.849
fig|158878.1.peg.233 0.904 0.916 0.936 0.893
fig|158878.1.peg.234 0.867 0.930 0.936 0.928
fig|158878.1.peg.235 0.838 0.849 0.893 0.928

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.231 3-ketoacyl-CoA thiolase (EC 2.3.1.16) Biotin_biosynthesis,CBSS-246196.1.peg.364,Isoleucine_degradation,Polyhydroxybutyrate_metabolism,Serine-glyoxylate_cycle,n-Phenylalkanoic_acid_degradation fig|158878.1.peg.232 Enoyl-CoA hydratase (EC 4.2.1.17) / Enoyl-CoA hydratase [valine degradation] (EC 4.2.1.17) / 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) Acetyl-CoA_fermentation_to_Butyrate,Butanol_Biosynthesis,Isoleucine_degradation,Polyhydroxybutyrate_metabolism,Valine_degradation,n-Phenylalkanoic_acid_degradation fig|158878.1.peg.233 Glutaryl-CoA dehydrogenase (EC 1.3.99.7) Anaerobic_benzoate_metabolism fig|158878.1.peg.234 Long-chain-fatty-acid--CoA ligase (EC 6.2.1.3) Biotin_biosynthesis,n-Phenylalkanoic_acid_degradation fig|158878.1.peg.235 hypothetical protein

At least, that is how I see it.


Pegs in Atomic Regulon 42 [ON=196 OFF=641]

Pearson Coefficients:
PEG peg.130 peg.131 peg.2662 peg.2663 peg.2664
fig|158878.1.peg.130 0.817 0.785 0.783 0.778
fig|158878.1.peg.131 0.817 0.770 0.751 0.794
fig|158878.1.peg.2662 0.785 0.770 0.861 0.811
fig|158878.1.peg.2663 0.783 0.751 0.861 0.814
fig|158878.1.peg.2664 0.778 0.794 0.811 0.814

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.130 Exopolysaccharide biosynthesis glycosyltransferase EpsF (EC 2.4.1.-) Exopolysaccharide_Biosynthesis fig|158878.1.peg.131 hypothetical protein fig|158878.1.peg.2662 Manganese-dependent protein-tyrosine phosphatase (EC 3.1.3.48) Cell_envelope-associated_LytR-CpsA-Psr_transcriptional_attenuators,Exopolysaccharide_Biosynthesis fig|158878.1.peg.2663 Tyrosine-protein kinase EpsD (EC 2.7.10.2) Cell_envelope-associated_LytR-CpsA-Psr_transcriptional_attenuators,Exopolysaccharide_Biosynthesis,Extracellular_Polysaccharide_Biosynthesis_of_Streptococci fig|158878.1.peg.2664 Capsular polysaccharide biosynthesis protein capA


In a state of almost total ignorance of the role of exopolysaccharides, I conjecture that both clusters of genes relate to that function, and peg.131 in particular relates to it.


Pegs in Atomic Regulon 61 [ON=243 OFF=588]


Pearson Coefficients:
PEG peg.329 peg.330 peg.331 peg.332
fig|158878.1.peg.329 0.826 0.749 0.805
fig|158878.1.peg.330 0.826 0.865 0.842
fig|158878.1.peg.331 0.749 0.865 0.868
fig|158878.1.peg.332 0.805 0.842 0.868

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.329 Putative sugar-specific permease, SgaT/UlaA fig|158878.1.peg.330 hypothetical protein fig|158878.1.peg.331 PTS system, IIA component fig|158878.1.peg.332 Putative transcriptional antiterminator, BglG family / PTS system, mannitol/fructose-specific IIA component (EC 2.7.1.69)

I claim that clusters like this are common and terribly difficult to analyze.

Connections for fig|158878.1.peg.329
PC PEG Function Subsystems
0.826 fig|158878.1.peg.330 hypothetical protein
0.805 fig|158878.1.peg.332 Putative transcriptional antiterminator, BglG family / PTS system, mannitol/fructose-specific IIA component (EC 2.7.1.69)
0.749 fig|158878.1.peg.331 PTS system, IIA component



Connections for fig|158878.1.peg.330
PC PEG Function Subsystems
0.865 fig|158878.1.peg.331 PTS system, IIA component
0.842 fig|158878.1.peg.332 Putative transcriptional antiterminator, BglG family / PTS system, mannitol/fructose-specific IIA component (EC 2.7.1.69)
0.826 fig|158878.1.peg.329 Putative sugar-specific permease, SgaT/UlaA
0.733 fig|158878.1.peg.2641 PTS system, mannose-specific IIB component (EC 2.7.1.69) / PTS system, mannose-specific IIC component (EC 2.7.1.69) / PTS system, mannose-specific IIA component (EC 2.7.1.69) Mannose_Metabolism,Sialic_Acid_Metabolism



Connections for fig|158878.1.peg.331
PC PEG Function Subsystems
0.868 fig|158878.1.peg.332 Putative transcriptional antiterminator, BglG family / PTS system, mannitol/fructose-specific IIA component (EC 2.7.1.69)
0.865 fig|158878.1.peg.330 hypothetical protein
0.749 fig|158878.1.peg.329 Putative sugar-specific permease, SgaT/UlaA
0.714 fig|158878.1.peg.2641 PTS system, mannose-specific IIB component (EC 2.7.1.69) / PTS system, mannose-specific IIC component (EC 2.7.1.69) / PTS system, mannose-specific IIA component (EC 2.7.1.69) Mannose_Metabolism,Sialic_Acid_Metabolism



Connections for fig|158878.1.peg.332
PC PEG Function Subsystems
0.868 fig|158878.1.peg.331 PTS system, IIA component
0.842 fig|158878.1.peg.330 hypothetical protein
0.805 fig|158878.1.peg.329 Putative sugar-specific permease, SgaT/UlaA
0.752 fig|158878.1.peg.2641 PTS system, mannose-specific IIB component (EC 2.7.1.69) / PTS system, mannose-specific IIC component (EC 2.7.1.69) / PTS system, mannose-specific IIA component (EC 2.7.1.69) Mannose_Metabolism,Sialic_Acid_Metabolism



Connections for fig|158878.1.peg.2641
PC PEG Function Subsystems
0.752 fig|158878.1.peg.332 Putative transcriptional antiterminator, BglG family / PTS system, mannitol/fructose-specific IIA component (EC 2.7.1.69)
0.733 fig|158878.1.peg.330 hypothetical protein
0.714 fig|158878.1.peg.331 PTS system, IIA component



I believe that peg.2641 and peg.2642 are co-regulated:

Pearson Coefficients:
PEG peg.2641 peg.2642
fig|158878.1.peg.2641 0.671
fig|158878.1.peg.2642 0.671

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.2641 PTS system, mannose-specific IIB component (EC 2.7.1.69) / PTS system, mannose-specific IIC component (EC 2.7.1.69) / PTS system, mannose-specific IIA component (EC 2.7.1.69) Mannose_Metabolism,Sialic_Acid_Metabolism fig|158878.1.peg.2642 Mannose-6-phosphate isomerase (EC 5.3.1.8) Alginate_metabolism,Mannose_Metabolism

This really does not cure our problem, but it does offer clues. In particular, it seems like a good bet that whatever peg.2641 is used to transport is the substrate of this PTS module. Let us examine the evidence: This "evidence" reflects the total uncertainty annotators experience when trying to guess the substrate of a PTS module. However, I believe that peg.330 is the IIB subunit, and the substrate is probably mannose. The mannose-6-phosphate is converted to fructose-6-phosphate by the mannose-6-phosphate isomerase, and the fructose-6-phosphate flows into glycolysis.

My reasoning is essentially as follows:
  1. The substrate of the PTS module is completely undetermined, although we can nail down the subunits.
  2. The expression correlations and clustering point directly at peg.2642 as the consumer of the substrate.
  3. peg.2642 appears to have the solid function Mannose-6-phosphate isomerase (EC 5.3.1.8).
  4. The import of mannose-6-phosphate, conversion to fructose-6-phosphate, and then catabolizing that via glycolysis is a simple model.

It would be good to check some of the conditions to verify that mannose was in the growth media. However, we do have about 196 experiments registering ON and 641 OFF, so maybe checking a few samples would help determine whether or not my model is accurate.

It is also worth mentioning that the PTS module might be capable of transporting both mannose (to mannose-6-phosphate) and fructose to (fructose-6-phosphate). That would explain the ambiguity in determining its substrate and would fit the model (more-or-less).

Pegs in Atomic Regulon 87 [ON=778 OFF=57]

Here is a strange situation. I started with a 3-gene cluster of hypotheticals. I asked "What do these correlate with?". I stopped expanding with these.
Pearson Coefficients:
PEG peg.2182 peg.2183 peg.2184 peg.2085 peg.1739 peg.823 peg.1854 peg.497 peg.372 peg.1752 peg.1839 peg.1214 peg.2382 peg.2368 peg.613 peg.997 peg.387 peg.1707 peg.682 peg.1881 peg.1625 peg.616 peg.1103 peg.1617 peg.1624 peg.998 peg.840 peg.1446 peg.2064 peg.1861 peg.1083 peg.1738 peg.1616 peg.1875 peg.1084 peg.704 peg.767 peg.1481 peg.1406 peg.1717 peg.1706 peg.2474 peg.1447 peg.766 peg.615 peg.2325
fig|158878.1.peg.2182 0.950 0.939 0.850 0.874 0.842 0.866 0.865 0.837 0.828 0.811 0.817 0.780 0.767 0.797 0.850 0.755 0.781 0.782 0.792 0.807 0.771 0.765 0.760 0.774 0.750 0.845 0.773 0.754 0.773 0.780 0.694 0.766 0.773 0.778 0.764 0.730 0.813 0.755 0.707 0.755 0.738 0.772 0.749 0.760 0.738
fig|158878.1.peg.2183 0.950 0.950 0.860 0.883 0.898 0.879 0.851 0.856 0.830 0.822 0.808 0.829 0.807 0.813 0.793 0.791 0.783 0.780 0.782 0.806 0.765 0.746 0.747 0.793 0.727 0.829 0.762 0.740 0.736 0.755 0.729 0.747 0.757 0.742 0.766 0.745 0.806 0.762 0.702 0.739 0.753 0.759 0.769 0.765 0.724
fig|158878.1.peg.2184 0.939 0.950 0.862 0.845 0.883 0.858 0.841 0.832 0.778 0.830 0.818 0.806 0.780 0.806 0.779 0.785 0.739 0.777 0.752 0.744 0.702 0.768 0.738 0.764 0.699 0.760 0.722 0.722 0.705 0.741 0.664 0.745 0.752 0.752 0.742 0.765 0.816 0.772 0.683 0.693 0.702 0.744 0.800 0.733 0.733
fig|158878.1.peg.2085 0.850 0.860 0.862 0.846 0.878 0.857 0.817 0.790 0.819 0.814 0.879 0.835 0.808 0.895 0.799 0.839 0.740 0.800 0.744 0.778 0.776 0.823 0.773 0.785 0.762 0.772 0.742 0.697 0.829 0.722 0.675 0.804 0.763 0.710 0.764 0.788 0.802 0.774 0.714 0.794 0.717 0.753 0.770 0.762 0.846
fig|158878.1.peg.1739 0.874 0.883 0.845 0.846 0.863 0.915 0.887 0.818 0.859 0.862 0.824 0.832 0.802 0.820 0.840 0.756 0.794 0.851 0.836 0.818 0.860 0.817 0.797 0.773 0.807 0.789 0.799 0.784 0.798 0.822 0.757 0.820 0.810 0.810 0.798 0.735 0.787 0.785 0.762 0.777 0.710 0.783 0.730 0.748 0.762
fig|158878.1.peg.823 0.842 0.898 0.883 0.878 0.863 0.864 0.809 0.830 0.802 0.824 0.845 0.891 0.829 0.854 0.748 0.853 0.737 0.775 0.711 0.748 0.747 0.752 0.701 0.774 0.707 0.715 0.668 0.677 0.753 0.650 0.697 0.738 0.802 0.642 0.769 0.807 0.763 0.784 0.668 0.700 0.723 0.703 0.798 0.777 0.760
fig|158878.1.peg.1854 0.866 0.879 0.858 0.857 0.915 0.864 0.882 0.864 0.883 0.890 0.820 0.838 0.846 0.848 0.820 0.795 0.813 0.865 0.849 0.831 0.823 0.850 0.828 0.805 0.822 0.793 0.809 0.825 0.815 0.821 0.778 0.853 0.860 0.804 0.850 0.799 0.819 0.825 0.807 0.782 0.728 0.808 0.805 0.778 0.813
fig|158878.1.peg.497 0.865 0.851 0.841 0.817 0.887 0.809 0.882 0.767 0.867 0.852 0.782 0.786 0.802 0.813 0.864 0.702 0.772 0.846 0.842 0.818 0.833 0.820 0.820 0.761 0.838 0.797 0.834 0.819 0.823 0.840 0.744 0.798 0.792 0.831 0.772 0.759 0.825 0.790 0.795 0.724 0.695 0.828 0.816 0.736 0.769
fig|158878.1.peg.372 0.837 0.856 0.832 0.790 0.818 0.830 0.864 0.767 0.837 0.807 0.757 0.812 0.826 0.749 0.689 0.742 0.822 0.816 0.797 0.859 0.738 0.735 0.725 0.868 0.714 0.825 0.697 0.745 0.706 0.679 0.779 0.685 0.798 0.656 0.763 0.721 0.700 0.695 0.694 0.768 0.827 0.660 0.718 0.752 0.700
fig|158878.1.peg.1752 0.828 0.830 0.778 0.819 0.859 0.802 0.883 0.867 0.837 0.779 0.742 0.776 0.860 0.840 0.792 0.734 0.812 0.832 0.863 0.858 0.885 0.809 0.814 0.830 0.842 0.831 0.840 0.845 0.817 0.791 0.811 0.783 0.760 0.779 0.763 0.748 0.762 0.769 0.827 0.794 0.781 0.804 0.749 0.725 0.799
fig|158878.1.peg.1839 0.811 0.822 0.830 0.814 0.862 0.824 0.890 0.852 0.807 0.779 0.850 0.849 0.815 0.824 0.818 0.759 0.805 0.797 0.786 0.769 0.757 0.791 0.778 0.768 0.759 0.755 0.729 0.745 0.771 0.775 0.738 0.776 0.829 0.776 0.766 0.745 0.767 0.773 0.737 0.767 0.652 0.705 0.763 0.741 0.762
fig|158878.1.peg.1214 0.817 0.808 0.818 0.879 0.824 0.845 0.820 0.782 0.757 0.742 0.850 0.862 0.787 0.865 0.815 0.834 0.782 0.720 0.690 0.718 0.720 0.712 0.672 0.717 0.701 0.743 0.634 0.597 0.805 0.636 0.650 0.712 0.773 0.637 0.774 0.755 0.736 0.713 0.636 0.776 0.695 0.662 0.745 0.780 0.741
fig|158878.1.peg.2382 0.780 0.829 0.806 0.835 0.832 0.891 0.838 0.786 0.812 0.776 0.849 0.862 0.826 0.831 0.729 0.822 0.789 0.760 0.720 0.766 0.752 0.700 0.691 0.798 0.708 0.736 0.637 0.646 0.745 0.615 0.763 0.686 0.776 0.593 0.756 0.784 0.696 0.722 0.636 0.686 0.737 0.644 0.782 0.784 0.716
fig|158878.1.peg.2368 0.767 0.807 0.780 0.808 0.802 0.829 0.846 0.802 0.826 0.860 0.815 0.787 0.826 0.877 0.758 0.838 0.827 0.785 0.757 0.791 0.792 0.748 0.773 0.833 0.788 0.789 0.748 0.745 0.792 0.686 0.860 0.710 0.725 0.670 0.774 0.775 0.747 0.762 0.786 0.760 0.765 0.724 0.784 0.708 0.769
fig|158878.1.peg.613 0.797 0.813 0.806 0.895 0.820 0.854 0.848 0.813 0.749 0.840 0.824 0.865 0.831 0.877 0.813 0.864 0.770 0.752 0.714 0.721 0.765 0.787 0.739 0.747 0.772 0.735 0.714 0.692 0.833 0.688 0.700 0.765 0.740 0.699 0.761 0.830 0.764 0.785 0.750 0.767 0.687 0.743 0.808 0.740 0.829
fig|158878.1.peg.997 0.850 0.793 0.779 0.799 0.840 0.748 0.820 0.864 0.689 0.792 0.818 0.815 0.729 0.758 0.813 0.688 0.741 0.722 0.746 0.745 0.792 0.751 0.791 0.669 0.807 0.793 0.760 0.748 0.845 0.786 0.656 0.788 0.758 0.774 0.690 0.675 0.754 0.752 0.745 0.755 0.595 0.748 0.681 0.703 0.737
fig|158878.1.peg.387 0.755 0.791 0.785 0.839 0.756 0.853 0.795 0.702 0.742 0.734 0.759 0.834 0.822 0.838 0.864 0.688 0.730 0.675 0.605 0.635 0.650 0.657 0.628 0.701 0.636 0.653 0.597 0.550 0.743 0.561 0.686 0.674 0.705 0.564 0.785 0.813 0.735 0.729 0.626 0.697 0.671 0.648 0.787 0.726 0.735
fig|158878.1.peg.1707 0.781 0.783 0.739 0.740 0.794 0.737 0.813 0.772 0.822 0.812 0.805 0.782 0.789 0.827 0.770 0.741 0.730 0.720 0.810 0.812 0.784 0.634 0.716 0.753 0.731 0.831 0.726 0.702 0.744 0.684 0.798 0.653 0.735 0.660 0.779 0.645 0.686 0.651 0.735 0.809 0.827 0.698 0.672 0.784 0.678
fig|158878.1.peg.682 0.782 0.780 0.777 0.800 0.851 0.775 0.865 0.846 0.816 0.832 0.797 0.720 0.760 0.785 0.752 0.722 0.675 0.720 0.848 0.831 0.826 0.854 0.844 0.813 0.842 0.742 0.811 0.813 0.777 0.809 0.771 0.809 0.798 0.788 0.813 0.741 0.792 0.782 0.807 0.728 0.682 0.770 0.760 0.677 0.802
fig|158878.1.peg.1881 0.792 0.782 0.752 0.744 0.836 0.711 0.849 0.842 0.797 0.863 0.786 0.690 0.720 0.757 0.714 0.746 0.605 0.810 0.848 0.869 0.857 0.786 0.847 0.779 0.831 0.807 0.873 0.863 0.780 0.847 0.757 0.777 0.751 0.810 0.768 0.617 0.718 0.700 0.833 0.770 0.756 0.811 0.670 0.704 0.738
fig|158878.1.peg.1625 0.807 0.806 0.744 0.778 0.818 0.748 0.831 0.818 0.859 0.858 0.769 0.718 0.766 0.791 0.721 0.745 0.635 0.812 0.831 0.869 0.855 0.738 0.826 0.902 0.821 0.930 0.832 0.811 0.788 0.768 0.851 0.722 0.743 0.700 0.721 0.634 0.693 0.674 0.768 0.781 0.813 0.732 0.670 0.745 0.710
fig|158878.1.peg.616 0.771 0.765 0.702 0.776 0.860 0.747 0.823 0.833 0.738 0.885 0.757 0.720 0.752 0.792 0.765 0.792 0.650 0.784 0.826 0.857 0.855 0.767 0.832 0.778 0.882 0.820 0.851 0.799 0.849 0.792 0.799 0.777 0.738 0.752 0.746 0.648 0.731 0.740 0.820 0.762 0.737 0.795 0.651 0.691 0.772
fig|158878.1.peg.1103 0.765 0.746 0.768 0.823 0.817 0.752 0.850 0.820 0.735 0.809 0.791 0.712 0.700 0.748 0.787 0.751 0.657 0.634 0.854 0.786 0.738 0.767 0.860 0.747 0.845 0.664 0.805 0.829 0.781 0.830 0.661 0.884 0.754 0.836 0.738 0.776 0.779 0.830 0.790 0.736 0.596 0.787 0.755 0.625 0.854
fig|158878.1.peg.1617 0.760 0.747 0.738 0.773 0.797 0.701 0.828 0.820 0.725 0.814 0.778 0.672 0.691 0.773 0.739 0.791 0.628 0.716 0.844 0.847 0.826 0.832 0.860 0.777 0.896 0.782 0.914 0.905 0.819 0.889 0.771 0.882 0.724 0.848 0.740 0.694 0.798 0.840 0.874 0.759 0.621 0.852 0.726 0.632 0.822
fig|158878.1.peg.1624 0.774 0.793 0.764 0.785 0.773 0.774 0.805 0.761 0.868 0.830 0.768 0.717 0.798 0.833 0.747 0.669 0.701 0.753 0.813 0.779 0.902 0.778 0.747 0.777 0.751 0.841 0.737 0.755 0.697 0.681 0.854 0.671 0.698 0.641 0.673 0.708 0.668 0.690 0.704 0.718 0.753 0.644 0.705 0.661 0.727
fig|158878.1.peg.998 0.750 0.727 0.699 0.762 0.807 0.707 0.822 0.838 0.714 0.842 0.759 0.701 0.708 0.788 0.772 0.807 0.636 0.731 0.842 0.831 0.821 0.882 0.845 0.896 0.751 0.776 0.870 0.859 0.884 0.815 0.769 0.847 0.775 0.792 0.764 0.708 0.779 0.822 0.872 0.767 0.648 0.827 0.717 0.690 0.835
fig|158878.1.peg.840 0.845 0.829 0.760 0.772 0.789 0.715 0.793 0.797 0.825 0.831 0.755 0.743 0.736 0.789 0.735 0.793 0.653 0.831 0.742 0.807 0.930 0.820 0.664 0.782 0.841 0.776 0.812 0.768 0.783 0.737 0.827 0.656 0.691 0.678 0.692 0.614 0.696 0.653 0.717 0.810 0.800 0.706 0.657 0.741 0.665
fig|158878.1.peg.1446 0.773 0.762 0.722 0.742 0.799 0.668 0.809 0.834 0.697 0.840 0.729 0.634 0.637 0.748 0.714 0.760 0.597 0.726 0.811 0.873 0.832 0.851 0.805 0.914 0.737 0.870 0.812 0.874 0.798 0.913 0.767 0.824 0.674 0.875 0.736 0.650 0.795 0.788 0.859 0.791 0.682 0.914 0.691 0.634 0.764
fig|158878.1.peg.2064 0.754 0.740 0.722 0.697 0.784 0.677 0.825 0.819 0.745 0.845 0.745 0.597 0.646 0.745 0.692 0.748 0.550 0.702 0.813 0.863 0.811 0.799 0.829 0.905 0.755 0.859 0.768 0.874 0.755 0.862 0.761 0.817 0.744 0.838 0.709 0.686 0.727 0.784 0.862 0.697 0.616 0.815 0.721 0.627 0.756
fig|158878.1.peg.1861 0.773 0.736 0.705 0.829 0.798 0.753 0.815 0.823 0.706 0.817 0.771 0.805 0.745 0.792 0.833 0.845 0.743 0.744 0.777 0.780 0.788 0.849 0.781 0.819 0.697 0.884 0.783 0.798 0.755 0.736 0.706 0.817 0.784 0.719 0.805 0.730 0.763 0.762 0.798 0.803 0.697 0.795 0.740 0.782 0.802
fig|158878.1.peg.1083 0.780 0.755 0.741 0.722 0.822 0.650 0.821 0.840 0.679 0.791 0.775 0.636 0.615 0.686 0.688 0.786 0.561 0.684 0.809 0.847 0.768 0.792 0.830 0.889 0.681 0.815 0.737 0.913 0.862 0.736 0.687 0.850 0.695 0.953 0.697 0.629 0.787 0.778 0.842 0.743 0.567 0.850 0.665 0.579 0.767
fig|158878.1.peg.1738 0.694 0.729 0.664 0.675 0.757 0.697 0.778 0.744 0.779 0.811 0.738 0.650 0.763 0.860 0.700 0.656 0.686 0.798 0.771 0.757 0.851 0.799 0.661 0.771 0.854 0.769 0.827 0.767 0.761 0.706 0.687 0.625 0.645 0.640 0.713 0.669 0.690 0.675 0.761 0.697 0.740 0.669 0.692 0.662 0.661
fig|158878.1.peg.1616 0.766 0.747 0.745 0.804 0.820 0.738 0.853 0.798 0.685 0.783 0.776 0.712 0.686 0.710 0.765 0.788 0.674 0.653 0.809 0.777 0.722 0.777 0.884 0.882 0.671 0.847 0.656 0.824 0.817 0.817 0.850 0.625 0.768 0.834 0.751 0.723 0.804 0.833 0.822 0.748 0.551 0.836 0.715 0.661 0.849
fig|158878.1.peg.1875 0.773 0.757 0.752 0.763 0.810 0.802 0.860 0.792 0.798 0.760 0.829 0.773 0.776 0.725 0.740 0.758 0.705 0.735 0.798 0.751 0.743 0.738 0.754 0.724 0.698 0.775 0.691 0.674 0.744 0.784 0.695 0.645 0.768 0.682 0.819 0.755 0.728 0.749 0.703 0.679 0.653 0.700 0.764 0.783 0.731
fig|158878.1.peg.1084 0.778 0.742 0.752 0.710 0.810 0.642 0.804 0.831 0.656 0.779 0.776 0.637 0.593 0.670 0.699 0.774 0.564 0.660 0.788 0.810 0.700 0.752 0.836 0.848 0.641 0.792 0.678 0.875 0.838 0.719 0.953 0.640 0.834 0.682 0.690 0.660 0.796 0.797 0.816 0.715 0.528 0.835 0.685 0.566 0.759
fig|158878.1.peg.704 0.764 0.766 0.742 0.764 0.798 0.769 0.850 0.772 0.763 0.763 0.766 0.774 0.756 0.774 0.761 0.690 0.785 0.779 0.813 0.768 0.721 0.746 0.738 0.740 0.673 0.764 0.692 0.736 0.709 0.805 0.697 0.713 0.751 0.819 0.690 0.778 0.766 0.745 0.737 0.736 0.748 0.772 0.790 0.785 0.737
fig|158878.1.peg.767 0.730 0.745 0.765 0.788 0.735 0.807 0.799 0.759 0.721 0.748 0.745 0.755 0.784 0.775 0.830 0.675 0.813 0.645 0.741 0.617 0.634 0.648 0.776 0.694 0.708 0.708 0.614 0.650 0.686 0.730 0.629 0.669 0.723 0.755 0.660 0.778 0.738 0.815 0.662 0.625 0.630 0.703 0.921 0.701 0.776
fig|158878.1.peg.1481 0.813 0.806 0.816 0.802 0.787 0.763 0.819 0.825 0.700 0.762 0.767 0.736 0.696 0.747 0.764 0.754 0.735 0.686 0.792 0.718 0.693 0.731 0.779 0.798 0.668 0.779 0.696 0.795 0.727 0.763 0.787 0.690 0.804 0.728 0.796 0.766 0.738 0.861 0.765 0.717 0.605 0.832 0.799 0.627 0.795
fig|158878.1.peg.1406 0.755 0.762 0.772 0.774 0.785 0.784 0.825 0.790 0.695 0.769 0.773 0.713 0.722 0.762 0.785 0.752 0.729 0.651 0.782 0.700 0.674 0.740 0.830 0.840 0.690 0.822 0.653 0.788 0.784 0.762 0.778 0.675 0.833 0.749 0.797 0.745 0.815 0.861 0.789 0.701 0.558 0.827 0.816 0.611 0.837
fig|158878.1.peg.1717 0.707 0.702 0.683 0.714 0.762 0.668 0.807 0.795 0.694 0.827 0.737 0.636 0.636 0.786 0.750 0.745 0.626 0.735 0.807 0.833 0.768 0.820 0.790 0.874 0.704 0.872 0.717 0.859 0.862 0.798 0.842 0.761 0.822 0.703 0.816 0.737 0.662 0.765 0.789 0.732 0.635 0.844 0.683 0.622 0.800
fig|158878.1.peg.1706 0.755 0.739 0.693 0.794 0.777 0.700 0.782 0.724 0.768 0.794 0.767 0.776 0.686 0.760 0.767 0.755 0.697 0.809 0.728 0.770 0.781 0.762 0.736 0.759 0.718 0.767 0.810 0.791 0.697 0.803 0.743 0.697 0.748 0.679 0.715 0.736 0.625 0.717 0.701 0.732 0.729 0.730 0.604 0.706 0.758
fig|158878.1.peg.2474 0.738 0.753 0.702 0.717 0.710 0.723 0.728 0.695 0.827 0.781 0.652 0.695 0.737 0.765 0.687 0.595 0.671 0.827 0.682 0.756 0.813 0.737 0.596 0.621 0.753 0.648 0.800 0.682 0.616 0.697 0.567 0.740 0.551 0.653 0.528 0.748 0.630 0.605 0.558 0.635 0.729 0.660 0.647 0.743 0.597
fig|158878.1.peg.1447 0.772 0.759 0.744 0.753 0.783 0.703 0.808 0.828 0.660 0.804 0.705 0.662 0.644 0.724 0.743 0.748 0.648 0.698 0.770 0.811 0.732 0.795 0.787 0.852 0.644 0.827 0.706 0.914 0.815 0.795 0.850 0.669 0.836 0.700 0.835 0.772 0.703 0.832 0.827 0.844 0.730 0.660 0.740 0.651 0.771
fig|158878.1.peg.766 0.749 0.769 0.800 0.770 0.730 0.798 0.805 0.816 0.718 0.749 0.763 0.745 0.782 0.784 0.808 0.681 0.787 0.672 0.760 0.670 0.670 0.651 0.755 0.726 0.705 0.717 0.657 0.691 0.721 0.740 0.665 0.692 0.715 0.764 0.685 0.790 0.921 0.799 0.816 0.683 0.604 0.647 0.740 0.711 0.748
fig|158878.1.peg.615 0.760 0.765 0.733 0.762 0.748 0.777 0.778 0.736 0.752 0.725 0.741 0.780 0.784 0.708 0.740 0.703 0.726 0.784 0.677 0.704 0.745 0.691 0.625 0.632 0.661 0.690 0.741 0.634 0.627 0.782 0.579 0.662 0.661 0.783 0.566 0.785 0.701 0.627 0.611 0.622 0.706 0.743 0.651 0.711 0.652
fig|158878.1.peg.2325 0.738 0.724 0.733 0.846 0.762 0.760 0.813 0.769 0.700 0.799 0.762 0.741 0.716 0.769 0.829 0.737 0.735 0.678 0.802 0.738 0.710 0.772 0.854 0.822 0.727 0.835 0.665 0.764 0.756 0.802 0.767 0.661 0.849 0.731 0.759 0.737 0.776 0.795 0.837 0.800 0.758 0.597 0.771 0.748 0.652

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.2182 alkaline shock protein 23 fig|158878.1.peg.2183 Hypothetical protein SAV2183 fig|158878.1.peg.2184 Hypothetical protein SAV2184 fig|158878.1.peg.2085 Hypothetical protein SAV2085 fig|158878.1.peg.1739 General stress protein-like protein fig|158878.1.peg.823 hypothetical protein fig|158878.1.peg.1854 Hypothetical protein SAV1854 fig|158878.1.peg.497 YabJ, a purine regulatory protein and member of the highly conserved YjgF family De_Novo_Purine_Biosynthesis fig|158878.1.peg.372 hypothetical protein fig|158878.1.peg.1752 Hypothetical protein SAV1752 fig|158878.1.peg.1839 Hypothetical protein SAV1839 At5g48545_and_At3g56490_At1g31160,CBSS-176279.3.peg.1262,EcsAB_transporter_affecting_expression_and_secretion_of_secretory_preproteins fig|158878.1.peg.1214 hypothetical protein fig|158878.1.peg.2382 General stress protein 26 fig|158878.1.peg.2368 hypothetical protein similar to TpgX fig|158878.1.peg.613 hypothetical protein fig|158878.1.peg.997 Regulatory protein spx fig|158878.1.peg.387 hypothetical protein fig|158878.1.peg.1707 FIG002379: metal-dependent hydrolase CBSS-269801.1.peg.809 fig|158878.1.peg.682 hypothetical protein fig|158878.1.peg.1881 FIG133424: Low molecular weight protein tyrosine phosphatase (EC 3.1.3.48) CBSS-176280.1.peg.1561,LMPTP_YfkJ_cluster fig|158878.1.peg.1625 sigmaB-controlled gene product fig|158878.1.peg.616 Staphylococcal accessory regulator A (SarA) Biofilm_formation_in_Staphylococcus fig|158878.1.peg.1103 hypothetical protein fig|158878.1.peg.1617 Hypothetical protein possible functionally linked with Alanyl-tRNA synthetase CBSS-257314.1.peg.488 fig|158878.1.peg.1624 hypothetical protein fig|158878.1.peg.998 Negative regulator of genetic competence MecA fig|158878.1.peg.840 hypothetical protein fig|158878.1.peg.1446 Cell division protein GpsB, coordinates the switch between cylindrical and septal cell wall synthesis by re-localization of PBP1 Control_of_cell_elongation_-_division_cycle_in_Bacilli fig|158878.1.peg.2064 RNA polymerase sigma factor SigB Biofilm_formation_in_Staphylococcus,Methicillin_resistance_in_Staphylococci,SigmaB_stress_responce_regulation,Transcription_initiation,_bacterial_sigma_factors fig|158878.1.peg.1861 Peroxide stress regulator PerR, FUR family Oxidative_stress,Putative_hemin_transporter fig|158878.1.peg.1083 Phosphocarrier protein of PTS system HPr_catabolite_repression_system,Mannitol_Utilization fig|158878.1.peg.1738 Maebl fig|158878.1.peg.1616 Putative Holliday junction resolvase (EC 3.1.-.-) CBSS-257314.1.peg.488,CBSS-281090.3.peg.464,CBSS-320372.3.peg.6046 fig|158878.1.peg.1875 ThiJ/PfpI family protein CBSS-176280.1.peg.1561,COG2363 fig|158878.1.peg.1084 Phosphoenolpyruvate-protein phosphotransferase of PTS system (EC 2.7.3.9) Mannitol_Utilization fig|158878.1.peg.704 CsbB stress response protein fig|158878.1.peg.767 FIG001886: Cytoplasmic hypothetical protein Cluster_containing_CofD-like_protein_and_co-occuring_with_DNA_repair fig|158878.1.peg.1481 Elastin binding protein EbpS Adhesins_in_Staphylococcus fig|158878.1.peg.1406 Tellurite resistance protein fig|158878.1.peg.1717 Septation ring formation regulator EzrA CBSS-393130.3.peg.794,Control_of_cell_elongation_-_division_cycle_in_Bacilli fig|158878.1.peg.1706 Universal stress protein family CBSS-269801.1.peg.809,Universal_stress_protein_family fig|158878.1.peg.2474 hypothetical protein fig|158878.1.peg.1447 FIG005686: hypothetical protein Control_of_cell_elongation_-_division_cycle_in_Bacilli fig|158878.1.peg.766 FIG002813: LPPG:FO 2-phospho-L-lactate transferase like, CofD-like Cluster_containing_CofD-like_protein_and_co-occuring_with_DNA_repair fig|158878.1.peg.615 hypothetical esterase/lipase [EC:3.1.-.-] fig|158878.1.peg.2325 Hypothetical protein SAV2325

I found that I was expanding into correlations between genes that tended to always be ON or OFF, I then wrote a simple expansion logic (which I call "broadening" a set of PEGs), and got:


Pearson Coefficients:
PEG peg.2182 peg.2183 peg.2184 peg.2085 peg.1214 peg.823 peg.1739 peg.1839 peg.372 peg.613 peg.2382 peg.1625 peg.840 peg.2368 peg.1707 peg.682 peg.387 peg.1624 peg.1881 peg.1875 peg.1861 peg.704 peg.1706 peg.766 peg.767 peg.615 peg.2325 peg.752 peg.498 peg.2334
fig|158878.1.peg.2182 0.950 0.939 0.850 0.817 0.842 0.874 0.811 0.837 0.797 0.780 0.807 0.845 0.767 0.781 0.782 0.755 0.774 0.792 0.773 0.773 0.764 0.755 0.749 0.730 0.760 0.738 0.712 0.766 0.690
fig|158878.1.peg.2183 0.950 0.950 0.860 0.808 0.898 0.883 0.822 0.856 0.813 0.829 0.806 0.829 0.807 0.783 0.780 0.791 0.793 0.782 0.757 0.736 0.766 0.739 0.769 0.745 0.765 0.724 0.715 0.726 0.717
fig|158878.1.peg.2184 0.939 0.950 0.862 0.818 0.883 0.845 0.830 0.832 0.806 0.806 0.744 0.760 0.780 0.739 0.777 0.785 0.764 0.752 0.752 0.705 0.742 0.693 0.800 0.765 0.733 0.733 0.672 0.678 0.727
fig|158878.1.peg.2085 0.850 0.860 0.862 0.879 0.878 0.846 0.814 0.790 0.895 0.835 0.778 0.772 0.808 0.740 0.800 0.839 0.785 0.744 0.763 0.829 0.764 0.794 0.770 0.788 0.762 0.846 0.728 0.713 0.728
fig|158878.1.peg.1214 0.817 0.808 0.818 0.879 0.845 0.824 0.850 0.757 0.865 0.862 0.718 0.743 0.787 0.782 0.720 0.834 0.717 0.690 0.773 0.805 0.774 0.776 0.745 0.755 0.780 0.741 0.767 0.743 0.758
fig|158878.1.peg.823 0.842 0.898 0.883 0.878 0.845 0.863 0.824 0.830 0.854 0.891 0.748 0.715 0.829 0.737 0.775 0.853 0.774 0.711 0.802 0.753 0.769 0.700 0.798 0.807 0.777 0.760 0.699 0.692 0.776
fig|158878.1.peg.1739 0.874 0.883 0.845 0.846 0.824 0.863 0.862 0.818 0.820 0.832 0.818 0.789 0.802 0.794 0.851 0.756 0.773 0.836 0.810 0.798 0.798 0.777 0.730 0.735 0.748 0.762 0.718 0.776 0.692
fig|158878.1.peg.1839 0.811 0.822 0.830 0.814 0.850 0.824 0.862 0.807 0.824 0.849 0.769 0.755 0.815 0.805 0.797 0.759 0.768 0.786 0.829 0.771 0.766 0.767 0.763 0.745 0.741 0.762 0.742 0.767 0.728
fig|158878.1.peg.372 0.837 0.856 0.832 0.790 0.757 0.830 0.818 0.807 0.749 0.812 0.859 0.825 0.826 0.822 0.816 0.742 0.868 0.797 0.798 0.706 0.763 0.768 0.718 0.721 0.752 0.700 0.709 0.709 0.715
fig|158878.1.peg.613 0.797 0.813 0.806 0.895 0.865 0.854 0.820 0.824 0.749 0.831 0.721 0.735 0.877 0.770 0.752 0.864 0.747 0.714 0.740 0.833 0.761 0.767 0.808 0.830 0.740 0.829 0.814 0.734 0.771
fig|158878.1.peg.2382 0.780 0.829 0.806 0.835 0.862 0.891 0.832 0.849 0.812 0.831 0.766 0.736 0.826 0.789 0.760 0.822 0.798 0.720 0.776 0.745 0.756 0.686 0.782 0.784 0.784 0.716 0.737 0.739 0.779
fig|158878.1.peg.1625 0.807 0.806 0.744 0.778 0.718 0.748 0.818 0.769 0.859 0.721 0.766 0.930 0.791 0.812 0.831 0.635 0.902 0.869 0.743 0.788 0.721 0.781 0.670 0.634 0.745 0.710 0.751 0.812 0.585
fig|158878.1.peg.840 0.845 0.829 0.760 0.772 0.743 0.715 0.789 0.755 0.825 0.735 0.736 0.930 0.789 0.831 0.742 0.653 0.841 0.807 0.691 0.783 0.692 0.810 0.657 0.614 0.741 0.665 0.815 0.822 0.595
fig|158878.1.peg.2368 0.767 0.807 0.780 0.808 0.787 0.829 0.802 0.815 0.826 0.877 0.826 0.791 0.789 0.827 0.785 0.838 0.833 0.757 0.725 0.792 0.774 0.760 0.784 0.775 0.708 0.769 0.842 0.750 0.776
fig|158878.1.peg.1707 0.781 0.783 0.739 0.740 0.782 0.737 0.794 0.805 0.822 0.770 0.789 0.812 0.831 0.827 0.720 0.730 0.753 0.810 0.735 0.744 0.779 0.809 0.672 0.645 0.784 0.678 0.809 0.793 0.707
fig|158878.1.peg.682 0.782 0.780 0.777 0.800 0.720 0.775 0.851 0.797 0.816 0.752 0.760 0.831 0.742 0.785 0.720 0.675 0.813 0.848 0.798 0.777 0.813 0.728 0.760 0.741 0.677 0.802 0.687 0.727 0.665
fig|158878.1.peg.387 0.755 0.791 0.785 0.839 0.834 0.853 0.756 0.759 0.742 0.864 0.822 0.635 0.653 0.838 0.730 0.675 0.701 0.605 0.705 0.743 0.785 0.697 0.787 0.813 0.726 0.735 0.762 0.653 0.847
fig|158878.1.peg.1624 0.774 0.793 0.764 0.785 0.717 0.774 0.773 0.768 0.868 0.747 0.798 0.902 0.841 0.833 0.753 0.813 0.701 0.779 0.698 0.697 0.673 0.718 0.705 0.708 0.661 0.727 0.713 0.708 0.624
fig|158878.1.peg.1881 0.792 0.782 0.752 0.744 0.690 0.711 0.836 0.786 0.797 0.714 0.720 0.869 0.807 0.757 0.810 0.848 0.605 0.779 0.751 0.780 0.768 0.770 0.670 0.617 0.704 0.738 0.688 0.781 0.582
fig|158878.1.peg.1875 0.773 0.757 0.752 0.763 0.773 0.802 0.810 0.829 0.798 0.740 0.776 0.743 0.691 0.725 0.735 0.798 0.705 0.698 0.751 0.784 0.819 0.679 0.764 0.755 0.783 0.731 0.655 0.772 0.767
fig|158878.1.peg.1861 0.773 0.736 0.705 0.829 0.805 0.753 0.798 0.771 0.706 0.833 0.745 0.788 0.783 0.792 0.744 0.777 0.743 0.697 0.780 0.784 0.805 0.803 0.740 0.730 0.782 0.802 0.789 0.832 0.690
fig|158878.1.peg.704 0.764 0.766 0.742 0.764 0.774 0.769 0.798 0.766 0.763 0.761 0.756 0.721 0.692 0.774 0.779 0.813 0.785 0.673 0.768 0.819 0.805 0.736 0.790 0.778 0.785 0.737 0.727 0.761 0.817
fig|158878.1.peg.1706 0.755 0.739 0.693 0.794 0.776 0.700 0.777 0.767 0.768 0.767 0.686 0.781 0.810 0.760 0.809 0.728 0.697 0.718 0.770 0.679 0.803 0.736 0.604 0.625 0.706 0.758 0.741 0.694 0.601
fig|158878.1.peg.766 0.749 0.769 0.800 0.770 0.745 0.798 0.730 0.763 0.718 0.808 0.782 0.670 0.657 0.784 0.672 0.760 0.787 0.705 0.670 0.764 0.740 0.790 0.604 0.921 0.711 0.748 0.711 0.714 0.832
fig|158878.1.peg.767 0.730 0.745 0.765 0.788 0.755 0.807 0.735 0.745 0.721 0.830 0.784 0.634 0.614 0.775 0.645 0.741 0.813 0.708 0.617 0.755 0.730 0.778 0.625 0.921 0.701 0.776 0.672 0.662 0.818
fig|158878.1.peg.615 0.760 0.765 0.733 0.762 0.780 0.777 0.748 0.741 0.752 0.740 0.784 0.745 0.741 0.708 0.784 0.677 0.726 0.661 0.704 0.783 0.782 0.785 0.706 0.711 0.701 0.652 0.704 0.789 0.776
fig|158878.1.peg.2325 0.738 0.724 0.733 0.846 0.741 0.760 0.762 0.762 0.700 0.829 0.716 0.710 0.665 0.769 0.678 0.802 0.735 0.727 0.738 0.731 0.802 0.737 0.758 0.748 0.776 0.652 0.669 0.643 0.658
fig|158878.1.peg.752 0.712 0.715 0.672 0.728 0.767 0.699 0.718 0.742 0.709 0.814 0.737 0.751 0.815 0.842 0.809 0.687 0.762 0.713 0.688 0.655 0.789 0.727 0.741 0.711 0.672 0.704 0.669 0.778 0.706
fig|158878.1.peg.498 0.766 0.726 0.678 0.713 0.743 0.692 0.776 0.767 0.709 0.734 0.739 0.812 0.822 0.750 0.793 0.727 0.653 0.708 0.781 0.772 0.832 0.761 0.694 0.714 0.662 0.789 0.643 0.778 0.694
fig|158878.1.peg.2334 0.690 0.717 0.727 0.728 0.758 0.776 0.692 0.728 0.715 0.771 0.779 0.585 0.595 0.776 0.707 0.665 0.847 0.624 0.582 0.767 0.690 0.817 0.601 0.832 0.818 0.776 0.658 0.706 0.694

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.2182 alkaline shock protein 23 fig|158878.1.peg.2183 Hypothetical protein SAV2183 fig|158878.1.peg.2184 Hypothetical protein SAV2184 fig|158878.1.peg.2085 Hypothetical protein SAV2085 fig|158878.1.peg.1214 hypothetical protein fig|158878.1.peg.823 hypothetical protein fig|158878.1.peg.1739 General stress protein-like protein fig|158878.1.peg.1839 Hypothetical protein SAV1839 At5g48545_and_At3g56490_At1g31160,CBSS-176279.3.peg.1262,EcsAB_transporter_affecting_expression_and_secretion_of_secretory_preproteins fig|158878.1.peg.372 hypothetical protein fig|158878.1.peg.613 hypothetical protein fig|158878.1.peg.2382 General stress protein 26 fig|158878.1.peg.1625 sigmaB-controlled gene product fig|158878.1.peg.840 hypothetical protein fig|158878.1.peg.2368 hypothetical protein similar to TpgX fig|158878.1.peg.1707 FIG002379: metal-dependent hydrolase CBSS-269801.1.peg.809 fig|158878.1.peg.682 hypothetical protein fig|158878.1.peg.387 hypothetical protein fig|158878.1.peg.1624 hypothetical protein fig|158878.1.peg.1881 FIG133424: Low molecular weight protein tyrosine phosphatase (EC 3.1.3.48) CBSS-176280.1.peg.1561,LMPTP_YfkJ_cluster fig|158878.1.peg.1875 ThiJ/PfpI family protein CBSS-176280.1.peg.1561,COG2363 fig|158878.1.peg.1861 Peroxide stress regulator PerR, FUR family Oxidative_stress,Putative_hemin_transporter fig|158878.1.peg.704 CsbB stress response protein fig|158878.1.peg.1706 Universal stress protein family CBSS-269801.1.peg.809,Universal_stress_protein_family fig|158878.1.peg.766 FIG002813: LPPG:FO 2-phospho-L-lactate transferase like, CofD-like Cluster_containing_CofD-like_protein_and_co-occuring_with_DNA_repair fig|158878.1.peg.767 FIG001886: Cytoplasmic hypothetical protein Cluster_containing_CofD-like_protein_and_co-occuring_with_DNA_repair fig|158878.1.peg.615 hypothetical esterase/lipase [EC:3.1.-.-] fig|158878.1.peg.2325 Hypothetical protein SAV2325 fig|158878.1.peg.752 Ribosomal subunit interface protein Biotin_biosynthesis_Experimental,Ribosome_activity_modulation,YhgH fig|158878.1.peg.498 Protein of unknown function identified by role in sporulation (SpoVG) Sporulation-associated_proteins_with_broader_functions fig|158878.1.peg.2334 Formiminoglutamase (EC 3.5.3.8) Experimental_-_Histidine_Degradation,Histidine_Degradation

These are still strange. You have a highly correlated set of essentially hypothetical proteins.


Pegs in Atomic Regulon 94 [ON=395 OFF=385]



Let me pursue this theme a bit further. Atomic regulon 94 began as just these three hypothetical proteins. I could find no meaningful or suggestive hits against characterized proteins or domains.
Pearson Coefficients:
PEG peg.1110 peg.1111 peg.1112
fig|158878.1.peg.1110 0.818 0.814
fig|158878.1.peg.1111 0.818 0.791
fig|158878.1.peg.1112 0.814 0.791

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.1110 hypothetical protein fig|158878.1.peg.1111 hypothetical protein fig|158878.1.peg.1112 hypothetical protein

Then I tried to expand the set to include just genes that that showed significant correlation scorres. I got the following:
Pearson Coefficients:
PEG peg.1110 peg.1111 peg.1112 peg.1845 peg.1332 peg.1615 peg.1626
fig|158878.1.peg.1110 0.818 0.814 0.826 0.812 0.793 0.728
fig|158878.1.peg.1111 0.818 0.791 0.823 0.787 0.727 0.786
fig|158878.1.peg.1112 0.814 0.791 0.843 0.832 0.817 0.810
fig|158878.1.peg.1845 0.826 0.823 0.843 0.814 0.792 0.799
fig|158878.1.peg.1332 0.812 0.787 0.832 0.814 0.787 0.755
fig|158878.1.peg.1615 0.793 0.727 0.817 0.792 0.787 0.732
fig|158878.1.peg.1626 0.728 0.786 0.810 0.799 0.755 0.732

Functions in Staphylococcus aureus subsp. aureus Mu50 PEG Function Subsystems fig|158878.1.peg.1110 hypothetical protein fig|158878.1.peg.1111 hypothetical protein fig|158878.1.peg.1112 hypothetical protein fig|158878.1.peg.1845 Hypothetical protein SAV1845 fig|158878.1.peg.1332 hypothetical protein fig|158878.1.peg.1615 hypothetical protein fig|158878.1.peg.1626 Iron-sulfur cluster regulator IscR At5g37530,Fe-S_cluster_assembly,Flavohaemoglobin,Iron-sulfur_cluster_assembly,Rrf2_family_transcriptional_regulators

Again, we have a bunch of hypotheticals and (in this case) a regulator that may, or may not, be accurately characterized.

Pegs in Atomic Regulon 97 [ON=163 OFF=655]




These seem quite innocent. When you ask for hits against characterized domains, all three show solid hits against a domain characterized as superantigen-like protein. If we start with this set of hypotheticals and "broaden" it,

Pearson Coefficients:
PEG peg.1166 peg.1167 peg.1168
fig|158878.1.peg.1166 0.875 0.873
fig|158878.1.peg.1167 0.875 0.908
fig|158878.1.peg.1168 0.873 0.908

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.1166 hypothetical protein
fig|158878.1.peg.1167 hypothetical protein
fig|158878.1.peg.1168 hypothetical protein


we get

Pearson Coefficients:
PEG peg.1166 peg.1167 peg.1168 peg.423 peg.1156 peg.427 peg.813 peg.428 peg.370 peg.426 peg.429 peg.1937
fig|158878.1.peg.1166 0.875 0.873 0.804 0.777 0.757 0.790 0.727 0.747 0.718 0.714 0.714
fig|158878.1.peg.1167 0.875 0.908 0.794 0.754 0.739 0.781 0.729 0.726 0.720 0.693 0.668
fig|158878.1.peg.1168 0.873 0.908 0.818 0.766 0.769 0.796 0.769 0.749 0.722 0.752 0.682
fig|158878.1.peg.423 0.804 0.794 0.818 0.783 0.819 0.766 0.835 0.780 0.754 0.823 0.714
fig|158878.1.peg.1156 0.777 0.754 0.766 0.783 0.758 0.804 0.710 0.847 0.747 0.737 0.827
fig|158878.1.peg.427 0.757 0.739 0.769 0.819 0.758 0.676 0.813 0.743 0.797 0.794 0.704
fig|158878.1.peg.813 0.790 0.781 0.796 0.766 0.804 0.676 0.654 0.859 0.680 0.757 0.822
fig|158878.1.peg.428 0.727 0.729 0.769 0.835 0.710 0.813 0.654 0.652 0.733 0.771 0.605
fig|158878.1.peg.370 0.747 0.726 0.749 0.780 0.847 0.743 0.859 0.652 0.652 0.836 0.882
fig|158878.1.peg.426 0.718 0.720 0.722 0.754 0.747 0.797 0.680 0.733 0.652 0.651 0.600
fig|158878.1.peg.429 0.714 0.693 0.752 0.823 0.737 0.794 0.757 0.771 0.836 0.651 0.753
fig|158878.1.peg.1937 0.714 0.668 0.682 0.714 0.827 0.704 0.822 0.605 0.882 0.600 0.753

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.1166 hypothetical protein
fig|158878.1.peg.1167 hypothetical protein
fig|158878.1.peg.1168 hypothetical protein
fig|158878.1.peg.423 Exotoxin 7
fig|158878.1.peg.1156 FIG017917: hypothetical protein
fig|158878.1.peg.427 Exotoxin 12
fig|158878.1.peg.813 Extracellular ECM and plasma binding protein Emp Adhesins_in_Staphylococcus
fig|158878.1.peg.428 Exotoxin 13
fig|158878.1.peg.370 hypothetical protein
fig|158878.1.peg.426 Exotoxin 1
fig|158878.1.peg.429 Exotoxin 4
fig|158878.1.peg.1937 Extracellular adherence protein of broad specificity Eap/Map Adhesins_in_Staphylococcus


Here we see that with a modest amount of effort, one could build this into a coherent, informative picture.


Pegs in Atomic Regulon 100 [ON=89 OFF=757]


Here is another small, innocent looking set of three genes.
Pearson Coefficients:
PEG peg.413 peg.414 peg.415
fig|158878.1.peg.413 0.886 0.814
fig|158878.1.peg.414 0.886 0.853
fig|158878.1.peg.415 0.814 0.853

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
fig|158878.1.peg.415 Transposase


When we "broaden it", we get

Pearson Coefficients:
PEG peg.413 peg.414 peg.415 peg.399 peg.411 peg.406 peg.408 peg.392 peg.398 peg.410 peg.402 peg.397 peg.401 peg.404 peg.412 peg.395 peg.405 peg.400 peg.407 peg.403 peg.409 peg.394
fig|158878.1.peg.413 0.886 0.814 0.806 0.829 0.873 0.836 0.896 0.841 0.822 0.829 0.852 0.805 0.875 0.810 0.817 0.827 0.818 0.814 0.810 0.788 0.776
fig|158878.1.peg.414 0.886 0.853 0.849 0.850 0.862 0.845 0.890 0.841 0.837 0.849 0.844 0.816 0.878 0.841 0.812 0.850 0.829 0.809 0.829 0.825 0.822
fig|158878.1.peg.415 0.814 0.853 0.833 0.917 0.824 0.864 0.832 0.842 0.808 0.905 0.803 0.890 0.806 0.907 0.806 0.910 0.905 0.838 0.796 0.927 0.877
fig|158878.1.peg.399 0.806 0.849 0.833 0.855 0.826 0.880 0.823 0.840 0.872 0.878 0.829 0.841 0.829 0.843 0.812 0.855 0.859 0.820 0.863 0.835 0.797
fig|158878.1.peg.411 0.829 0.850 0.917 0.855 0.847 0.898 0.836 0.881 0.858 0.925 0.844 0.904 0.823 0.911 0.827 0.925 0.924 0.876 0.858 0.920 0.870
fig|158878.1.peg.406 0.873 0.862 0.824 0.826 0.847 0.840 0.862 0.845 0.830 0.842 0.861 0.816 0.868 0.835 0.795 0.838 0.842 0.825 0.835 0.816 0.792
fig|158878.1.peg.408 0.836 0.845 0.864 0.880 0.898 0.840 0.837 0.886 0.898 0.924 0.846 0.892 0.836 0.877 0.836 0.907 0.925 0.898 0.902 0.886 0.826
fig|158878.1.peg.392 0.896 0.890 0.832 0.823 0.836 0.862 0.837 0.839 0.833 0.832 0.847 0.821 0.884 0.837 0.811 0.830 0.829 0.816 0.811 0.806 0.810
fig|158878.1.peg.398 0.841 0.841 0.842 0.840 0.881 0.845 0.886 0.839 0.870 0.895 0.864 0.860 0.838 0.847 0.800 0.889 0.885 0.871 0.870 0.852 0.819
fig|158878.1.peg.410 0.822 0.837 0.808 0.872 0.858 0.830 0.898 0.833 0.870 0.878 0.843 0.839 0.842 0.838 0.827 0.874 0.884 0.869 0.904 0.841 0.804
fig|158878.1.peg.402 0.829 0.849 0.905 0.878 0.925 0.842 0.924 0.832 0.895 0.878 0.840 0.911 0.827 0.903 0.824 0.937 0.932 0.903 0.878 0.914 0.869
fig|158878.1.peg.397 0.852 0.844 0.803 0.829 0.844 0.861 0.846 0.847 0.864 0.843 0.840 0.815 0.850 0.829 0.807 0.830 0.843 0.814 0.841 0.809 0.790
fig|158878.1.peg.401 0.805 0.816 0.890 0.841 0.904 0.816 0.892 0.821 0.860 0.839 0.911 0.815 0.787 0.900 0.778 0.899 0.913 0.870 0.832 0.913 0.847
fig|158878.1.peg.404 0.875 0.878 0.806 0.829 0.823 0.868 0.836 0.884 0.838 0.842 0.827 0.850 0.787 0.814 0.816 0.831 0.821 0.808 0.838 0.787 0.802
fig|158878.1.peg.412 0.810 0.841 0.907 0.843 0.911 0.835 0.877 0.837 0.847 0.838 0.903 0.829 0.900 0.814 0.807 0.897 0.902 0.850 0.836 0.915 0.885
fig|158878.1.peg.395 0.817 0.812 0.806 0.812 0.827 0.795 0.836 0.811 0.800 0.827 0.824 0.807 0.778 0.816 0.807 0.821 0.823 0.795 0.818 0.797 0.797
fig|158878.1.peg.405 0.827 0.850 0.910 0.855 0.925 0.838 0.907 0.830 0.889 0.874 0.937 0.830 0.899 0.831 0.897 0.821 0.924 0.894 0.860 0.913 0.862
fig|158878.1.peg.400 0.818 0.829 0.905 0.859 0.924 0.842 0.925 0.829 0.885 0.884 0.932 0.843 0.913 0.821 0.902 0.823 0.924 0.901 0.889 0.925 0.858
fig|158878.1.peg.407 0.814 0.809 0.838 0.820 0.876 0.825 0.898 0.816 0.871 0.869 0.903 0.814 0.870 0.808 0.850 0.795 0.894 0.901 0.872 0.865 0.823
fig|158878.1.peg.403 0.810 0.829 0.796 0.863 0.858 0.835 0.902 0.811 0.870 0.904 0.878 0.841 0.832 0.838 0.836 0.818 0.860 0.889 0.872 0.836 0.787
fig|158878.1.peg.409 0.788 0.825 0.927 0.835 0.920 0.816 0.886 0.806 0.852 0.841 0.914 0.809 0.913 0.787 0.915 0.797 0.913 0.925 0.865 0.836 0.883
fig|158878.1.peg.394 0.776 0.822 0.877 0.797 0.870 0.792 0.826 0.810 0.819 0.804 0.869 0.790 0.847 0.802 0.885 0.797 0.862 0.858 0.823 0.787 0.883

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.413 ATP-dependent DNA helicase pcrA (EC 3.6.1.-) CBSS-393121.3.peg.1913,DNA_repair,_bacterial_UvrD_and_related_helicases
fig|158878.1.peg.414 FIG131328: Predicted ATP-dependent endonuclease of the OLD family
fig|158878.1.peg.415 Transposase
fig|158878.1.peg.399 hypothetical protein
fig|158878.1.peg.411 hypothetical protein
fig|158878.1.peg.406 hypothetical protein
fig|158878.1.peg.408 hypothetical protein
fig|158878.1.peg.392 Integrase
fig|158878.1.peg.398 Tetracycline resistance protein TetM Tetracycline_resistance,_ribosome_protection_type,Translation_elongation_factor_G_family
fig|158878.1.peg.410 hypothetical protein
fig|158878.1.peg.402 hypothetical protein
fig|158878.1.peg.397 hypothetical protein
fig|158878.1.peg.401 hypothetical protein
fig|158878.1.peg.404 hypothetical protein
fig|158878.1.peg.412 hypothetical protein
fig|158878.1.peg.395 hypothetical protein
fig|158878.1.peg.405 hypothetical protein
fig|158878.1.peg.400 lipoprotein, NLP/P60 family
fig|158878.1.peg.407 FIG086557: Conjugation related protein
fig|158878.1.peg.403 hypothetical protein
fig|158878.1.peg.409 hypothetical protein
fig|158878.1.peg.394 hhypothetical protein


What is revealed is a pretty large cluster of genes that probably play a role in pathogenicity. A skilled annotator would spot this without needing the expression data, but with the expression data a mechanical protocol can easily lay these clusters out to be consistently annotated.

Pegs in Atomic Regulon 102 [ON=197 OFF=643]


Pearson Coefficients:
PEG peg.1811 peg.1812 peg.1813
fig|158878.1.peg.1811 0.875 0.873
fig|158878.1.peg.1812 0.875 0.888
fig|158878.1.peg.1813 0.873 0.888

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.1811 serine protease SplC
fig|158878.1.peg.1812 serine protease SplB
fig|158878.1.peg.1813 Serine protease SplA


Here again we have a set of three seemingly isolated genes. When we "broaden" the set, we get

Pearson Coefficients:
PEG peg.1811 peg.1812 peg.1813 peg.1820 peg.1819
fig|158878.1.peg.1811 0.875 0.873 0.739 0.727
fig|158878.1.peg.1812 0.875 0.888 0.754 0.771
fig|158878.1.peg.1813 0.873 0.888 0.745 0.793
fig|158878.1.peg.1820 0.739 0.754 0.745 0.880
fig|158878.1.peg.1819 0.727 0.771 0.793 0.880

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.1811 serine protease SplC
fig|158878.1.peg.1812 serine protease SplB
fig|158878.1.peg.1813 Serine protease SplA
fig|158878.1.peg.1820 Leukotoxin LukE Staphylococcus_Two-component_and_Pore-forming_Cytolysins
fig|158878.1.peg.1819 Leukotoxin LukD Staphylococcus_Two-component_and_Pore-forming_Cytolysins


Here, we link two groups of genes, both associated with virulence (see Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infection for a discussion). Most importantly, the link just falls out. No skill or insight was needed).

Pegs in Atomic Regulon 103 [ON=222 OFF=610]



Here is a simple example. We have three genes that all seem to be poorly characterized.
Pearson Coefficients:
PEG peg.2468 peg.2469 peg.2470
fig|158878.1.peg.2468 0.840 0.817
fig|158878.1.peg.2469 0.840 0.853
fig|158878.1.peg.2470 0.817 0.853

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.2468 FIG018700: hypothetical protein CBSS-208964.1.peg.4832
fig|158878.1.peg.2469 FIG016157: Similar to nicotianamine synthase CBSS-208964.1.peg.4832
fig|158878.1.peg.2470 FIG016473: Diaminopimelate epimerase homolog CBSS-208964.1.peg.4832


When we "broaden" the set, we get

Pearson Coefficients:
PEG peg.2468 peg.2469 peg.2470 peg.2466 peg.2463 peg.2465 peg.2467 peg.2464
fig|158878.1.peg.2468 0.840 0.817 0.729 0.699 0.744 0.661 0.619
fig|158878.1.peg.2469 0.840 0.853 0.757 0.714 0.648 0.691 0.664
fig|158878.1.peg.2470 0.817 0.853 0.760 0.722 0.710 0.719 0.688
fig|158878.1.peg.2466 0.729 0.757 0.760 0.807 0.799 0.823 0.794
fig|158878.1.peg.2463 0.699 0.714 0.722 0.807 0.748 0.764 0.858
fig|158878.1.peg.2465 0.744 0.648 0.710 0.799 0.748 0.735 0.720
fig|158878.1.peg.2467 0.661 0.691 0.719 0.823 0.764 0.735 0.725
fig|158878.1.peg.2464 0.619 0.664 0.688 0.794 0.858 0.720 0.725

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.2468 FIG018700: hypothetical protein CBSS-208964.1.peg.4832
fig|158878.1.peg.2469 FIG016157: Similar to nicotianamine synthase CBSS-208964.1.peg.4832
fig|158878.1.peg.2470 FIG016473: Diaminopimelate epimerase homolog CBSS-208964.1.peg.4832
fig|158878.1.peg.2466 Oligopeptide transporter putative membrane permease domain
fig|158878.1.peg.2463 Oligopeptide transporter putative ATPase domain
fig|158878.1.peg.2465 Oligopeptide transporter putative membrane permease domain
fig|158878.1.peg.2467 Oligopeptide transporter putative substrate binding domain
fig|158878.1.peg.2464 Oligopeptide transporter putative ATPase domain


Here we see that we should be looking at a single big cluster from peg.2464 to peg.2470. The cluster encodes a 5-gene transport along with 3 genes that do something associated. Is that it? Well, maybe not. If you take the transport genes and look for domains, what you find is that the substrate-binding gene (peg.2467 has a very strong hit against a a domain that is described as

PBP2_NikA : The substrate-binding component of an ABC-type nickel import system contains the type 2 periplasmic binding fold The substrate-binding component of an ABC-type nickel import system contains the type 2 periplasmic binding fold. This family represents the periplasmic substrate-binding domain of nickel transport system, which functions in the import of nickel and in the control of chemotactic response away from nickel. The ATP-binding cassette (ABC) type nickel transport system is comprised of five subunits NikABCDE: the two pore-forming integral inner membrane proteins NikB and NikC; the two inner membrane-associated proteins with ATPase activity NikD and NikE; and the periplasmic nickel binding NikA, the initial nickel receptor. The oligopeptide-binding protein OppA and the dipeptide-binding protein DppA show significant sequence similarity to NikA. The DppA binds dipeptides and some tripeptides and is involved in chemotaxis toward dipeptides, whereas the OppA binds peptides of a wide range of lengths (2-35 amino acid residues) and plays a role in recycling of cell wall peptides, which precludes any involvement in chemotaxis. Most of other periplasmic binding proteins are comprised of only two globular subdomains corresponding to domains I and III of the dipeptide/oligopeptide binding proteins. The structural topology of these domains is most similar to that of the type 2 periplasmic binding proteins (PBP2), which are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the ligand-binding domains from ionotropic glutamate receptors, LysR-type transcriptional regulators, and unorthodox sensor proteins involved in signal transduction.


If we look at A nickel ABC-transporter of Staphylococcus aureus is involved in urinary tract infection we see

Summary

The oligopeptide transport systems Opp belong to the
nickel/peptide/opine PepT subfamily of ABC-transporters. The
opportunist pathogen Staphylococcus aureus encodes four putative Opps
and one orphean substrate binding protein Opp5A. Here, we report that
the Opp2 permease complex (Opp2BCDF) and Opp5A are involved in nickel
uptake and then renamed them NikBCDE and NikA respectively. S. aureus
carries also a high-affinity nickel transporter NixA belonging to the
NiCoT family of secondary transporters. The activity of these two
nickel transporters determine that of urease, a multimeric
nickel-dependent enzyme mainly involved in the neutralization of
acidic environments. However, only the Nik system was responsible for
the neutralization and deposit of pH-dependent crystals in human
urine. Inactivation of the nik genes affected bacterial colonization
of mouse urinary tract, as well as the 50% infective dose levels
compared with the parental and nixA strains. Finally, complementation
of the nik mutations restored bacterial colonization. Together, our
results suggest a role for the Nik system in the urinary tract
infection by S. aureus, probably due to the urease-mediated pH
increase of the urine.


Note that what I am saying is that the three nontransport genes may be implicated in a nickel-related activity. Someone who understands the role of nickel in the cell needs to look at this.

Pegs in Atomic Regulon 105 [ON=107 OFF=738]




Here, again, we have what looks like a small cluster of hypotheticals.

Pearson Coefficients:
PEG peg.75 peg.76 peg.77
fig|158878.1.peg.75 0.901 0.777
fig|158878.1.peg.76 0.901 0.832
fig|158878.1.peg.77 0.777 0.832

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.75 hypothetical protein
fig|158878.1.peg.76 hypothetical protein
fig|158878.1.peg.77 hypothetical protein


But, when we broaden it we get

Pearson Coefficients:
PEG peg.75 peg.76 peg.77 peg.72 peg.69 peg.49 peg.47 peg.57 peg.74 peg.46 peg.44 peg.71 peg.80 peg.70 peg.34 peg.81 peg.58 peg.45 peg.31 peg.35 peg.64 peg.60 peg.67 peg.73 peg.33 peg.68 peg.63 peg.32 peg.866
fig|158878.1.peg.75 0.901 0.777 0.901 0.886 0.802 0.824 0.817 0.861 0.803 0.811 0.879 0.867 0.889 0.767 0.872 0.791 0.798 0.769 0.758 0.742 0.746 0.791 0.765 0.725 0.766 0.693 0.684 0.723
fig|158878.1.peg.76 0.901 0.832 0.929 0.912 0.854 0.864 0.854 0.880 0.844 0.833 0.898 0.869 0.882 0.817 0.863 0.823 0.838 0.791 0.789 0.782 0.776 0.790 0.768 0.753 0.756 0.728 0.760 0.764
fig|158878.1.peg.77 0.777 0.832 0.807 0.829 0.832 0.773 0.797 0.786 0.792 0.778 0.754 0.798 0.753 0.804 0.734 0.791 0.781 0.705 0.727 0.755 0.806 0.693 0.606 0.790 0.639 0.735 0.773 0.667
fig|158878.1.peg.72 0.901 0.929 0.807 0.922 0.850 0.878 0.850 0.879 0.862 0.839 0.925 0.867 0.871 0.827 0.871 0.835 0.838 0.806 0.815 0.805 0.754 0.778 0.799 0.740 0.769 0.738 0.740 0.773
fig|158878.1.peg.69 0.886 0.912 0.829 0.922 0.844 0.857 0.826 0.857 0.844 0.814 0.890 0.869 0.870 0.823 0.864 0.810 0.815 0.770 0.790 0.795 0.746 0.778 0.760 0.741 0.756 0.728 0.740 0.746
fig|158878.1.peg.49 0.802 0.854 0.832 0.850 0.844 0.863 0.849 0.818 0.875 0.857 0.821 0.832 0.793 0.905 0.796 0.830 0.863 0.834 0.850 0.810 0.810 0.720 0.647 0.793 0.684 0.787 0.765 0.685
fig|158878.1.peg.47 0.824 0.864 0.773 0.878 0.857 0.863 0.892 0.848 0.877 0.869 0.857 0.787 0.796 0.836 0.812 0.861 0.864 0.847 0.836 0.826 0.789 0.748 0.774 0.778 0.769 0.759 0.771 0.746
fig|158878.1.peg.57 0.817 0.854 0.797 0.850 0.826 0.849 0.892 0.826 0.865 0.866 0.802 0.805 0.778 0.793 0.777 0.869 0.881 0.808 0.772 0.812 0.838 0.751 0.680 0.795 0.749 0.785 0.737 0.702
fig|158878.1.peg.74 0.861 0.880 0.786 0.879 0.857 0.818 0.848 0.826 0.802 0.824 0.859 0.831 0.878 0.790 0.858 0.785 0.819 0.815 0.804 0.748 0.745 0.797 0.799 0.762 0.816 0.691 0.684 0.752
fig|158878.1.peg.46 0.803 0.844 0.792 0.862 0.844 0.875 0.877 0.865 0.802 0.853 0.821 0.807 0.782 0.828 0.793 0.841 0.832 0.795 0.804 0.816 0.794 0.723 0.669 0.763 0.706 0.772 0.740 0.696
fig|158878.1.peg.44 0.811 0.833 0.778 0.839 0.814 0.857 0.869 0.866 0.824 0.853 0.806 0.806 0.783 0.826 0.806 0.829 0.875 0.839 0.819 0.810 0.794 0.751 0.697 0.784 0.720 0.758 0.699 0.700
fig|158878.1.peg.71 0.879 0.898 0.754 0.925 0.890 0.821 0.857 0.802 0.859 0.821 0.806 0.834 0.871 0.830 0.903 0.769 0.793 0.835 0.846 0.754 0.662 0.749 0.846 0.669 0.747 0.666 0.696 0.757
fig|158878.1.peg.80 0.867 0.869 0.798 0.867 0.869 0.832 0.787 0.805 0.831 0.807 0.806 0.834 0.844 0.780 0.848 0.794 0.806 0.743 0.723 0.748 0.792 0.788 0.683 0.741 0.728 0.714 0.660 0.674
fig|158878.1.peg.70 0.889 0.882 0.753 0.871 0.870 0.793 0.796 0.778 0.878 0.782 0.783 0.871 0.844 0.779 0.870 0.742 0.763 0.806 0.794 0.701 0.698 0.776 0.770 0.706 0.762 0.652 0.639 0.688
fig|158878.1.peg.34 0.767 0.817 0.804 0.827 0.823 0.905 0.836 0.793 0.790 0.828 0.826 0.830 0.780 0.779 0.795 0.784 0.816 0.880 0.929 0.789 0.731 0.659 0.661 0.757 0.638 0.737 0.750 0.661
fig|158878.1.peg.81 0.872 0.863 0.734 0.871 0.864 0.796 0.812 0.777 0.858 0.793 0.806 0.903 0.848 0.870 0.795 0.733 0.775 0.816 0.810 0.723 0.657 0.782 0.784 0.654 0.772 0.651 0.569 0.737
fig|158878.1.peg.58 0.791 0.823 0.791 0.835 0.810 0.830 0.861 0.869 0.785 0.841 0.829 0.769 0.794 0.742 0.784 0.733 0.840 0.753 0.746 0.845 0.880 0.727 0.646 0.799 0.706 0.826 0.778 0.739
fig|158878.1.peg.45 0.798 0.838 0.781 0.838 0.815 0.863 0.864 0.881 0.819 0.832 0.875 0.793 0.806 0.763 0.816 0.775 0.840 0.822 0.777 0.802 0.819 0.756 0.697 0.781 0.730 0.769 0.724 0.708
fig|158878.1.peg.31 0.769 0.791 0.705 0.806 0.770 0.834 0.847 0.808 0.815 0.795 0.839 0.835 0.743 0.806 0.880 0.816 0.753 0.822 0.928 0.740 0.679 0.700 0.773 0.727 0.696 0.674 0.650 0.644
fig|158878.1.peg.35 0.758 0.789 0.727 0.815 0.790 0.850 0.836 0.772 0.804 0.804 0.819 0.846 0.723 0.794 0.929 0.810 0.746 0.777 0.928 0.746 0.649 0.659 0.748 0.723 0.659 0.671 0.689 0.662
fig|158878.1.peg.64 0.742 0.782 0.755 0.805 0.795 0.810 0.826 0.812 0.748 0.816 0.810 0.754 0.748 0.701 0.789 0.723 0.845 0.802 0.740 0.746 0.774 0.660 0.610 0.737 0.660 0.845 0.724 0.707
fig|158878.1.peg.60 0.746 0.776 0.806 0.754 0.746 0.810 0.789 0.838 0.745 0.794 0.794 0.662 0.792 0.698 0.731 0.657 0.880 0.819 0.679 0.649 0.774 0.703 0.503 0.827 0.658 0.809 0.743 0.619
fig|158878.1.peg.67 0.791 0.790 0.693 0.778 0.778 0.720 0.748 0.751 0.797 0.723 0.751 0.749 0.788 0.776 0.659 0.782 0.727 0.756 0.700 0.659 0.660 0.703 0.690 0.663 0.819 0.680 0.584 0.663
fig|158878.1.peg.73 0.765 0.768 0.606 0.799 0.760 0.647 0.774 0.680 0.799 0.669 0.697 0.846 0.683 0.770 0.661 0.784 0.646 0.697 0.773 0.748 0.610 0.503 0.690 0.563 0.729 0.479 0.590 0.719
fig|158878.1.peg.33 0.725 0.753 0.790 0.740 0.741 0.793 0.778 0.795 0.762 0.763 0.784 0.669 0.741 0.706 0.757 0.654 0.799 0.781 0.727 0.723 0.737 0.827 0.663 0.563 0.660 0.734 0.767 0.596
fig|158878.1.peg.68 0.766 0.756 0.639 0.769 0.756 0.684 0.769 0.749 0.816 0.706 0.720 0.747 0.728 0.762 0.638 0.772 0.706 0.730 0.696 0.659 0.660 0.658 0.819 0.729 0.660 0.654 0.567 0.729
fig|158878.1.peg.63 0.693 0.728 0.735 0.738 0.728 0.787 0.759 0.785 0.691 0.772 0.758 0.666 0.714 0.652 0.737 0.651 0.826 0.769 0.674 0.671 0.845 0.809 0.680 0.479 0.734 0.654 0.670 0.612
fig|158878.1.peg.32 0.684 0.760 0.773 0.740 0.740 0.765 0.771 0.737 0.684 0.740 0.699 0.696 0.660 0.639 0.750 0.569 0.778 0.724 0.650 0.689 0.724 0.743 0.584 0.590 0.767 0.567 0.670 0.587
fig|158878.1.peg.866 0.723 0.764 0.667 0.773 0.746 0.685 0.746 0.702 0.752 0.696 0.700 0.757 0.674 0.688 0.661 0.737 0.739 0.708 0.644 0.662 0.707 0.619 0.663 0.719 0.596 0.729 0.612 0.587

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.75 hypothetical protein
fig|158878.1.peg.76 hypothetical protein
fig|158878.1.peg.77 hypothetical protein
fig|158878.1.peg.72 Potassium-transporting ATPase A chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
fig|158878.1.peg.69 Conserved hypothetical protein
fig|158878.1.peg.49 FIG003846: hypothetical protein Disulphide_related_cluster
fig|158878.1.peg.47 Disulfide bond regulator Disulphide_related_cluster
fig|158878.1.peg.57 DNA repair protein RadC truncated by transposon Tn554
fig|158878.1.peg.74 Potassium-transporting ATPase C chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
fig|158878.1.peg.46 Zn-dependent hydroxyacylglutathione hydrolase Disulphide_related_cluster
fig|158878.1.peg.44 Putative ROK-family transcriptional regulator
fig|158878.1.peg.71 Osmosensitive K+ channel histidine kinase KdpD (EC 2.7.3.-) Potassium_homeostasis
fig|158878.1.peg.80 hypothetical protein
fig|158878.1.peg.70 DNA-binding response regulator KdpE
fig|158878.1.peg.34 Bleomycin resistance protein
fig|158878.1.peg.81 hypothetical protein
fig|158878.1.peg.58 hypothetical protein
fig|158878.1.peg.45 Polysulfide binding protein Disulphide_related_cluster
fig|158878.1.peg.31 Plasmid recombination enzyme
fig|158878.1.peg.35 Kanamycin nucleotidyltransferase (EC 2.7.7.-)
fig|158878.1.peg.64 hypothetical protein
fig|158878.1.peg.60 hypothetical protein
fig|158878.1.peg.67 Transposase of Staphylococcus aureus IS150 element
fig|158878.1.peg.73 Potassium-transporting ATPase B chain (EC 3.6.3.12) (TC 3.A.3.7.1) Potassium_homeostasis
fig|158878.1.peg.33 hypothetical protein
fig|158878.1.peg.68 Transposase
fig|158878.1.peg.63 hypothetical protein
fig|158878.1.peg.32 hypothetical protein
fig|158878.1.peg.866 Hypothetical protein, PV83 orf19 homolog [SA bacteriophages 11, Mu50B] Staphylococcal_phi-Mu50B-like_prophages


Again, we see a glimpse of machinery related to stress, and perhaps playing a role in interaction with the host.

Pegs in Atomic Regulon 109 [ON=177 OFF=651]



This is again a small group that can easily be broadened into a larger cluster that more accurately depicts a prophage:
Pearson Coefficients:
PEG peg.1985 peg.1986 peg.1987
fig|158878.1.peg.1985 0.836 0.779
fig|158878.1.peg.1986 0.836 0.835
fig|158878.1.peg.1987 0.779 0.835

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.1985 Recombinational DNA repair protein RecT (prophage associated) DNA_repair,_bacterial
fig|158878.1.peg.1986 ATPase involved in DNA repair, phage associated
fig|158878.1.peg.1987 Bacteriophage


Here is the larger cluster:

Pearson Coefficients:
PEG peg.1985 peg.1986 peg.1987 peg.1984 peg.1983 peg.1981 peg.1980 peg.1982 peg.1991 peg.1969
fig|158878.1.peg.1985 0.836 0.779 0.782 0.858 0.868 0.861 0.713 0.837 0.677
fig|158878.1.peg.1986 0.836 0.835 0.912 0.932 0.902 0.847 0.808 0.710 0.727
fig|158878.1.peg.1987 0.779 0.835 0.829 0.828 0.813 0.803 0.783 0.699 0.660
fig|158878.1.peg.1984 0.782 0.912 0.829 0.890 0.848 0.821 0.822 0.699 0.699
fig|158878.1.peg.1983 0.858 0.932 0.828 0.890 0.935 0.879 0.818 0.745 0.745
fig|158878.1.peg.1981 0.868 0.902 0.813 0.848 0.935 0.859 0.770 0.738 0.727
fig|158878.1.peg.1980 0.861 0.847 0.803 0.821 0.879 0.859 0.785 0.781 0.754
fig|158878.1.peg.1982 0.713 0.808 0.783 0.822 0.818 0.770 0.785 0.623 0.660
fig|158878.1.peg.1991 0.837 0.710 0.699 0.699 0.745 0.738 0.781 0.623 0.712
fig|158878.1.peg.1969 0.677 0.727 0.660 0.699 0.745 0.727 0.754 0.660 0.712

Functions in Staphylococcus aureus subsp. aureus Mu50
PEG Function Subsystems
fig|158878.1.peg.1985 Recombinational DNA repair protein RecT (prophage associated) DNA_repair,_bacterial
fig|158878.1.peg.1986 ATPase involved in DNA repair, phage associated
fig|158878.1.peg.1987 Bacteriophage
fig|158878.1.peg.1984 Metallo-beta-lactamase superfamily domain protein in prophage Heme,_hemin_uptake_and_utilization_systems_in_GramPositives
fig|158878.1.peg.1983 Single-stranded DNA-binding protein, phage associated
fig|158878.1.peg.1981 Bacteriophage
fig|158878.1.peg.1980 Phage Holliday junction resolvase
fig|158878.1.peg.1982 hypothetical protein within prophage
fig|158878.1.peg.1991 hypothetical protein within prophage
fig|158878.1.peg.1969 Bacteriophage




Switching to Shewanella for a while

Here is one from Shewanella. These genes are ON in 99 of 238 experiments that we have for Shewanells:

Pearson Coefficients: Get All Related PEGs
PEG peg.2690 peg.2691 peg.2692 peg.2693 peg.2694 peg.2695 peg.2696 peg.2697 peg.2698 peg.2699 peg.2700 peg.2701 peg.2702 peg.2682 peg.2680 peg.2683 peg.2681 peg.2675 peg.2689 peg.2684 peg.2707 peg.2677 peg.2676 peg.2688 peg.2679 peg.2704 peg.2705 peg.2706
fig|211586.9.peg.2690 0.895 0.905 0.865 0.909 0.904 0.845 0.838 0.840 0.873 0.811 0.748 0.713 0.828 0.859 0.819 0.852 0.735 0.865 0.835 0.680 0.754 0.746 0.735 0.715 0.705 0.667 0.703
fig|211586.9.peg.2691 0.895 0.966 0.950 0.927 0.928 0.894 0.906 0.868 0.888 0.928 0.833 0.744 0.845 0.856 0.850 0.865 0.828 0.826 0.738 0.709 0.778 0.760 0.709 0.776 0.623 0.639 0.650
fig|211586.9.peg.2692 0.905 0.966 0.955 0.936 0.949 0.904 0.918 0.895 0.902 0.924 0.880 0.788 0.874 0.862 0.860 0.894 0.820 0.845 0.776 0.765 0.768 0.768 0.737 0.763 0.652 0.666 0.702
fig|211586.9.peg.2693 0.865 0.950 0.955 0.939 0.956 0.920 0.941 0.917 0.910 0.945 0.907 0.812 0.906 0.872 0.892 0.904 0.841 0.857 0.801 0.818 0.767 0.771 0.786 0.770 0.694 0.732 0.711
fig|211586.9.peg.2694 0.909 0.927 0.936 0.939 0.979 0.959 0.969 0.930 0.944 0.886 0.859 0.742 0.916 0.863 0.898 0.883 0.850 0.926 0.859 0.812 0.775 0.739 0.816 0.732 0.775 0.811 0.798
fig|211586.9.peg.2695 0.904 0.928 0.949 0.956 0.979 0.950 0.967 0.926 0.935 0.900 0.879 0.769 0.929 0.877 0.897 0.895 0.840 0.905 0.853 0.828 0.775 0.743 0.817 0.729 0.768 0.804 0.788
fig|211586.9.peg.2696 0.845 0.894 0.904 0.920 0.959 0.950 0.971 0.957 0.953 0.892 0.903 0.780 0.908 0.856 0.917 0.884 0.901 0.907 0.831 0.814 0.804 0.767 0.812 0.778 0.799 0.849 0.809
fig|211586.9.peg.2697 0.838 0.906 0.918 0.941 0.969 0.967 0.971 0.945 0.949 0.910 0.904 0.774 0.929 0.850 0.913 0.885 0.887 0.909 0.844 0.850 0.792 0.748 0.829 0.754 0.784 0.833 0.802
fig|211586.9.peg.2698 0.840 0.868 0.895 0.917 0.930 0.926 0.957 0.945 0.963 0.893 0.917 0.811 0.916 0.876 0.924 0.915 0.886 0.908 0.862 0.822 0.842 0.820 0.821 0.821 0.822 0.846 0.817
fig|211586.9.peg.2699 0.873 0.888 0.902 0.910 0.944 0.935 0.953 0.949 0.963 0.897 0.891 0.809 0.892 0.867 0.894 0.896 0.866 0.895 0.859 0.822 0.851 0.798 0.797 0.812 0.821 0.830 0.834
fig|211586.9.peg.2700 0.811 0.928 0.924 0.945 0.886 0.900 0.892 0.910 0.893 0.897 0.918 0.837 0.844 0.835 0.825 0.864 0.818 0.777 0.706 0.782 0.780 0.766 0.670 0.795 0.658 0.691 0.653
fig|211586.9.peg.2701 0.748 0.833 0.880 0.907 0.859 0.879 0.903 0.904 0.917 0.891 0.918 0.858 0.871 0.815 0.870 0.875 0.833 0.803 0.747 0.859 0.754 0.777 0.743 0.775 0.718 0.768 0.721
fig|211586.9.peg.2702 0.713 0.744 0.788 0.812 0.742 0.769 0.780 0.774 0.811 0.809 0.837 0.858 0.760 0.751 0.782 0.803 0.726 0.717 0.709 0.722 0.712 0.746 0.650 0.747 0.705 0.667 0.616
fig|211586.9.peg.2682 0.828 0.845 0.874 0.906 0.916 0.929 0.908 0.929 0.916 0.892 0.844 0.871 0.760 0.869 0.941 0.912 0.851 0.926 0.907 0.847 0.770 0.763 0.901 0.728 0.771 0.819 0.740
fig|211586.9.peg.2680 0.859 0.856 0.862 0.872 0.863 0.877 0.856 0.850 0.876 0.867 0.835 0.815 0.751 0.869 0.869 0.930 0.847 0.835 0.825 0.683 0.872 0.903 0.762 0.867 0.737 0.715 0.642
fig|211586.9.peg.2683 0.819 0.850 0.860 0.892 0.898 0.897 0.917 0.913 0.924 0.894 0.825 0.870 0.782 0.941 0.869 0.919 0.899 0.927 0.896 0.777 0.791 0.813 0.883 0.776 0.787 0.801 0.718
fig|211586.9.peg.2681 0.852 0.865 0.894 0.904 0.883 0.895 0.884 0.885 0.915 0.896 0.864 0.875 0.803 0.912 0.930 0.919 0.867 0.868 0.869 0.763 0.868 0.877 0.795 0.852 0.764 0.738 0.708
fig|211586.9.peg.2675 0.735 0.828 0.820 0.841 0.850 0.840 0.901 0.887 0.886 0.866 0.818 0.833 0.726 0.851 0.847 0.899 0.867 0.827 0.762 0.719 0.876 0.849 0.769 0.849 0.708 0.755 0.687
fig|211586.9.peg.2689 0.865 0.826 0.845 0.857 0.926 0.905 0.907 0.909 0.908 0.895 0.777 0.803 0.717 0.926 0.835 0.927 0.868 0.827 0.931 0.789 0.743 0.728 0.926 0.692 0.816 0.837 0.794
fig|211586.9.peg.2684 0.835 0.738 0.776 0.801 0.859 0.853 0.831 0.844 0.862 0.859 0.706 0.747 0.709 0.907 0.825 0.896 0.869 0.762 0.931 0.765 0.754 0.713 0.890 0.676 0.834 0.810 0.786
fig|211586.9.peg.2707 0.680 0.709 0.765 0.818 0.812 0.828 0.814 0.850 0.822 0.822 0.782 0.859 0.722 0.847 0.683 0.777 0.763 0.719 0.789 0.765 0.612 0.575 0.804 0.563 0.725 0.826 0.792
fig|211586.9.peg.2677 0.754 0.778 0.768 0.767 0.775 0.775 0.804 0.792 0.842 0.851 0.780 0.754 0.712 0.770 0.872 0.791 0.868 0.876 0.743 0.754 0.612 0.897 0.647 0.925 0.706 0.660 0.663
fig|211586.9.peg.2676 0.746 0.760 0.768 0.771 0.739 0.743 0.767 0.748 0.820 0.798 0.766 0.777 0.746 0.763 0.903 0.813 0.877 0.849 0.728 0.713 0.575 0.897 0.655 0.903 0.661 0.605 0.546
fig|211586.9.peg.2688 0.735 0.709 0.737 0.786 0.816 0.817 0.812 0.829 0.821 0.797 0.670 0.743 0.650 0.901 0.762 0.883 0.795 0.769 0.926 0.890 0.804 0.647 0.655 0.596 0.736 0.795 0.706
fig|211586.9.peg.2679 0.715 0.776 0.763 0.770 0.732 0.729 0.778 0.754 0.821 0.812 0.795 0.775 0.747 0.728 0.867 0.776 0.852 0.849 0.692 0.676 0.563 0.925 0.903 0.596 0.627 0.568 0.566
fig|211586.9.peg.2704 0.705 0.623 0.652 0.694 0.775 0.768 0.799 0.784 0.822 0.821 0.658 0.718 0.705 0.771 0.737 0.787 0.764 0.708 0.816 0.834 0.725 0.706 0.661 0.736 0.627 0.899 0.842
fig|211586.9.peg.2705 0.667 0.639 0.666 0.732 0.811 0.804 0.849 0.833 0.846 0.830 0.691 0.768 0.667 0.819 0.715 0.801 0.738 0.755 0.837 0.810 0.826 0.660 0.605 0.795 0.568 0.899 0.857
fig|211586.9.peg.2706 0.703 0.650 0.702 0.711 0.798 0.788 0.809 0.802 0.817 0.834 0.653 0.721 0.616 0.740 0.642 0.718 0.708 0.687 0.794 0.786 0.792 0.663 0.546 0.706 0.566 0.842 0.857

Functions in Shewanella oneidensis MR-1
PEG Function Subsystems
fig|211586.9.peg.2690 hypothetical protein
fig|211586.9.peg.2691 hypothetical protein
fig|211586.9.peg.2692 hypothetical protein
fig|211586.9.peg.2693 hypothetical protein
fig|211586.9.peg.2694 hypothetical protein
fig|211586.9.peg.2695 hypothetical protein
fig|211586.9.peg.2696 Phage-related protein
fig|211586.9.peg.2697 hypothetical protein
fig|211586.9.peg.2698 prophage LambdaSo, DNA modification methyltransferase, putative
fig|211586.9.peg.2699 conserved hypothetical protein
fig|211586.9.peg.2700 C-5 cytosine-specific DNA methylase
fig|211586.9.peg.2701 hypothetical protein
fig|211586.9.peg.2702 hypothetical protein
fig|211586.9.peg.2682 hypothetical protein
fig|211586.9.peg.2680 phage replication protein O
fig|211586.9.peg.2683 hypothetical protein
fig|211586.9.peg.2681 hypothetical protein
fig|211586.9.peg.2675 uncharacterized phage protein
fig|211586.9.peg.2689 Plasmid pO157 DNA, complete sequence
fig|211586.9.peg.2684 conserved hypothetical protein
fig|211586.9.peg.2707 hypothetical protein
fig|211586.9.peg.2677 hypothetical protein
fig|211586.9.peg.2676 hypothetical protein
fig|211586.9.peg.2688 hypothetical protein
fig|211586.9.peg.2679 hypothetical protein
fig|211586.9.peg.2704 hypothetical protein
fig|211586.9.peg.2705 hypothetical protein
fig|211586.9.peg.2706 hypothetical protein


Pegs in Atomic Regulon 45 [ON=51 OFF=181]


Pearson Coefficients:
PEG peg.769 peg.770 peg.771 peg.772 peg.773
fig|211586.9.peg.769 0.918 0.833 0.853 0.661
fig|211586.9.peg.770 0.918 0.908 0.917 0.767
fig|211586.9.peg.771 0.833 0.908 0.938 0.831
fig|211586.9.peg.772 0.853 0.917 0.938 0.856
fig|211586.9.peg.773 0.661 0.767 0.831 0.856

Functions in Shewanella oneidensis MR-1
PEG Function Subsystems
fig|211586.9.peg.769 Type IV fimbrial biogenesis protein PilX Type_IV_pilus
fig|211586.9.peg.770 hypothetical protein
fig|211586.9.peg.771 Type IV fimbrial biogenesis protein PilV Type_IV_pilus
fig|211586.9.peg.772 Type IV fimbrial biogenesis protein FimT Type_IV_pilus
fig|211586.9.peg.773 Type IV pilus biogenesis protein PilE Type_IV_pilus


The hypothetical stands out, does it not?

Shewnella and Microcystins??



"Microcystins are cyclic nonribosomal peptides produced by cyanobacteria. They are cyanotoxins and can be very toxic for plants and animals including humans. " (Wikipedia)


The known bacteria that are able to affect the cyanobacterial growth include species such as Cytophaga, Shewanella, Streptomyces and Vibrio strains (Yamamoto et al. 1998, Yoshikawa et al. 2000, Rashidan and Bird 2001, Manage et al. 2000, Salomon et al. 2003). They can inhibit the cyanobacterial growth by means such as competition for limiting nutrients and by production of diffusible lytic compounds ...

cyanobacteria together with heterotrophic bacteria may represent an
increased health risk. The infection susceptibility of persons exposed
to cyanobacterial water blooms could be lowered by the adverse effects
of the cyanobacterial toxins. The lipopolysaccharides of the
Gram-negative bacteria, in turn, inhibit glutathione S-transferase
activity, which is important in detoxifying of microcystins, and may
increase the risk posed by the cyanobacterial hepatotoxins



Pearson Coefficients:
PEG peg.165 peg.166 peg.167 peg.168 peg.169 peg.163 peg.664 peg.1249
fig|211586.9.peg.165 0.950 0.931 0.866 0.670 0.794 0.796 0.686
fig|211586.9.peg.166 0.950 0.956 0.866 0.709 0.763 0.789 0.714
fig|211586.9.peg.167 0.931 0.956 0.884 0.724 0.793 0.781 0.718
fig|211586.9.peg.168 0.866 0.866 0.884 0.815 0.815 0.771 0.737
fig|211586.9.peg.169 0.670 0.709 0.724 0.815 0.718 0.581 0.592
fig|211586.9.peg.163 0.794 0.763 0.793 0.815 0.718 0.740 0.725
fig|211586.9.peg.664 0.796 0.789 0.781 0.771 0.581 0.740 0.739
fig|211586.9.peg.1249 0.686 0.714 0.718 0.737 0.592 0.725 0.739

Functions in Shewanella oneidensis MR-1
PEG Function Subsystems
fig|211586.9.peg.165 Microcystin dependent protein
fig|211586.9.peg.166 Microcystin dependent protein
fig|211586.9.peg.167 Microcystin dependent protein
fig|211586.9.peg.168 serine protease, subtilase family
fig|211586.9.peg.169 hypothetical protein
fig|211586.9.peg.163 hypothetical protein
fig|211586.9.peg.664 cold shock domain family protein
fig|211586.9.peg.1249 hypothetical protein

Why Are Such Conjectures Easy to Produce?

Now, let me proceed to the second point of this discussion: the factors that make it possible to produce hundreds of these conjectures for minimal effort. I must begin with an overview on how atomic regulons are computed:
  1. The processing begins by computing estimates of coregulated clusters. These estimates are based on two sources:
    1. estimates of co-expression based on position on the chromosome considered in the context of a set of expression experiments, and
    2. estimates of co-expression based on presence in the same row of a subsystem maintained within the SEED.
    These estimates might reasonably be called the initial set of putative atomic regulons.
  2. After the initial set is computed, a computation is run that tries to reconcile the raw expression values with these assertions. That is, we seek a set of ON/OFF calls for each gene, and then for each putative atomic regulon, that come as close as we can to the raw expression values.
  3. Once we have estimates for ON/OFF values for each atomic regulon in each experiment, we can compute a profile for each atomic regulon as a vector of ON/OFF values corresponding to the experiments. We can group merge an two putative atomic regulons with identical profiles, producing the final set of atomic regulons.
This simple process led to formation of 483 atomic regulons for E.coli. What is astounding is the wealth of information in just combining operon, subsystem, and expression data. There is a great deal to be offered by other forms of information, as I will argue a bit later in this document. However, I urge the reader not to focus on the available information that we did not use in the previous discussion (e.g., the actual conditions used in the experiments, metabolic modeling, or functional coupling data based on comparative analysis of many genomes); rather, focus on how much falls out of just quickly formed conjectures (i.e., potential operons and presence in a common subsystem) together with the expression data.

I would look to meander here to an example of how the addition of expression data to co-occurrence data can lead to useful refinements. To understand this short aside, you will need to briefly examine a set of PEGs in the E.coli genome. I would suggest going to fig|83333.1.peg.648. If you hover over genes in this region, you will note that a SEED annotator has placed genes peg.644 through peg.652 into a single, cluster-based subsystem. The reason was almost certainly that this large group of genes are in a fairly fixed cluster (but not an operon), and when there is no obvious "core" of the cluster. That is, when you look through the current genomes, you see the entire cluster within a close taxonomic group of the enteric bacteria, but the group does not extend much past that. There seemed to be value in recording the cluster, so a subsystem was formed. However, when we add expression data, we see the following correlation matrix:

Pearson Coefficients:
PEG peg.644 peg.645 peg.646 peg.647 peg.648 peg.649 peg.650 peg.651 peg.652
fig|83333.1.peg.644 0.235 -0.047 0.170 0.205 0.091 0.012 0.054 0.046
fig|83333.1.peg.645 0.235 0.603 0.622 0.713 0.557 0.669 0.472 -0.201
fig|83333.1.peg.646 -0.047 0.603 0.665 0.604 0.708 0.559 0.242 -0.214
fig|83333.1.peg.647 0.170 0.622 0.665 0.757 0.718 0.478 0.396 -0.126
fig|83333.1.peg.648 0.205 0.713 0.604 0.757 0.630 0.608 0.584 -0.063
fig|83333.1.peg.649 0.091 0.557 0.708 0.718 0.630 0.535 0.348 -0.156
fig|83333.1.peg.650 0.012 0.669 0.559 0.478 0.608 0.535 0.536 -0.163
fig|83333.1.peg.651 0.054 0.472 0.242 0.396 0.584 0.348 0.536 0.288
fig|83333.1.peg.652 0.046 -0.201 -0.214 -0.126 -0.063 -0.156 -0.163 0.288

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.644 Uncharacterized protein YbeL / FIG002095: hypothetical protein A_hypothetical_protein_that_co-occurs_with_Leucyl-tRNA_synthetase fig|83333.1.peg.645 Uncharacterized protein YbeQ fig|83333.1.peg.646 Uncharacterized protein YbeR fig|83333.1.peg.647 Uncharacterized J domain-containing protein YbeS, predicted chaperone fig|83333.1.peg.648 Uncharacterized protein YbeT fig|83333.1.peg.649 Uncharacterized protein YbeU fig|83333.1.peg.650 Uncharacterized J domain-containing protein YbeV fig|83333.1.peg.651 Chaperone protein hscC (Hsc62) fig|83333.1.peg.652 Pyrimidine-specific ribonucleoside hydrolase RihA (EC 3.2.-.-) Queuosine-Archaeosine_Biosynthesis

This changes the picture significantly. Notice that the first and last genes in the "cluster", peg.644 and peg.652, are clearly not related to the rest of the genes. peg.651 is pretty weakly related. This changes one's view of the significance of the cluster. Without the expression data, it was natural to wonder whether the group was related to the "pyrimidine-specific hydrolase RihA"; with the expression data, this notion should probably be discarded.

Let me show you another of these situations, lest you think my last one was an anomaly.

Pearson Coefficients:
PEG peg.699 peg.700 peg.701 peg.702 peg.703 peg.704 peg.705 peg.706
fig|83333.1.peg.699 0.587 0.165 0.373 0.283 0.300 0.165 -0.029
fig|83333.1.peg.700 0.587 0.284 0.290 0.191 0.239 0.182 0.015
fig|83333.1.peg.701 0.165 0.284 0.288 0.294 0.115 0.188 0.177
fig|83333.1.peg.702 0.373 0.290 0.288 0.890 0.820 0.672 0.230
fig|83333.1.peg.703 0.283 0.191 0.294 0.890 0.866 0.715 0.339
fig|83333.1.peg.704 0.300 0.239 0.115 0.820 0.866 0.790 0.418
fig|83333.1.peg.705 0.165 0.182 0.188 0.672 0.715 0.790 0.643
fig|83333.1.peg.706 -0.029 0.015 0.177 0.230 0.339 0.418 0.643

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.699 FIG143828: Hypothetical protein YbgA COG3380_COG2907,EC699-706 fig|83333.1.peg.700 Deoxyribodipyrimidine photolyase (EC 4.1.99.3) COG3380_COG2907,DNA_repair,_bacterial_photolyase,EC699-706 fig|83333.1.peg.701 Di/tripeptide permease YbgH EC699-706,Proton-dependent_Peptide_Transporters fig|83333.1.peg.702 FIG042796: Hypothetical protein EC699-706 fig|83333.1.peg.703 Allophanate hydrolase 2 subunit 1 (EC 3.5.1.54) EC699-706,Urea_carboxylase_and_Allophanate_hydrolase_cluster fig|83333.1.peg.704 Allophanate hydrolase 2 subunit 2 (EC 3.5.1.54) EC699-706,Urea_carboxylase_and_Allophanate_hydrolase_cluster fig|83333.1.peg.705 Lactam utilization protein LamB EC699-706 fig|83333.1.peg.706 Endonuclease VIII DNA_Repair_Base_Excision,EC699-706



Here it becomes apparent that the cluster is really peg.702 through peg.705. I believe that I was the author of the original, large cluster-based subsystem. In the presence of the expression data, I would have focused on the smaller cluster.

Before leaving this topic and returning to broader issues, let me bring your attention to the cluster including peg.3965 through peg.3967. You can view the cluster here.

Pearson Coefficients:
PEG peg.3965 peg.3966 peg.3967
fig|83333.1.peg.3965 0.174 0.143
fig|83333.1.peg.3966 0.174 0.904
fig|83333.1.peg.3967 0.143 0.904

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.3965 NMN phosphatase (EC 3.1.3.5); Class B acid phosphatase precursor (EC 3.1.3.2) NAD_and_NADP_cofactor_biosynthesis_global fig|83333.1.peg.3966 hypothetical protein fig|83333.1.peg.3967 Protein yjbR

It becomes obvious that peg.3965 is not co-expressed with the other two genes, which is quite unfortunate, since it was the gene with a function assigned to it.

I have shown a number of instances in which the information produced by the expression data was quite suggestive. I feel that I should also present one in which I can see no pattern at all, although the correlation coefficients are quite high:

Pearson Coefficients:
PEG peg.991 peg.1766 peg.2072 peg.2056 peg.798 peg.1174 peg.1881 peg.1722 peg.3296
fig|83333.1.peg.991 0.855 0.842 0.825 0.812 0.808 0.799 0.784 0.770
fig|83333.1.peg.1766 0.855 0.862 0.904 0.829 0.930 0.898 0.786 0.883
fig|83333.1.peg.2072 0.842 0.862 0.853 0.803 0.802 0.849 0.772 0.753
fig|83333.1.peg.2056 0.825 0.904 0.853 0.774 0.903 0.857 0.774 0.809
fig|83333.1.peg.798 0.812 0.829 0.803 0.774 0.741 0.794 0.833 0.822
fig|83333.1.peg.1174 0.808 0.930 0.802 0.903 0.741 0.833 0.725 0.832
fig|83333.1.peg.1881 0.799 0.898 0.849 0.857 0.794 0.833 0.784 0.869
fig|83333.1.peg.1722 0.784 0.786 0.772 0.774 0.833 0.725 0.784 0.809
fig|83333.1.peg.3296 0.770 0.883 0.753 0.809 0.822 0.832 0.869 0.809

Functions in Escherichia coli K12 PEG Function Subsystems fig|83333.1.peg.991 Flavoprotein wrbA fig|83333.1.peg.1766 Uncharacterized protein YeaG Unknown_carbohydrate_utilization_(_cluster_Ydj_) fig|83333.1.peg.2072 Fructose-bisphosphate aldolase class I (EC 4.1.2.13) Calvin-Benson_cycle,Formaldehyde_assimilation:_Ribulose_monophosphate_pathway,Glycolysis_and_Gluconeogenesis,Unknown_carbohydrate_utilization_(_cluster_Yeg_) fig|83333.1.peg.2056 hypothetical protein fig|83333.1.peg.798 Non-specific DNA-binding protein Dps / Iron-binding ferritin-like antioxidant protein / Ferroxidase (EC 1.16.3.1) Cobalt-zinc-cadmium_resistance,Oxidative_stress,YgfZ-Iron fig|83333.1.peg.1174 FIG004684: SpoVR-like protein fig|83333.1.peg.1881 Trehalose-6-phosphate phosphatase (EC 3.1.3.12) Trehalose_Biosynthesis fig|83333.1.peg.1722 Osmotically inducible lipoprotein E precursor fig|83333.1.peg.3296 Cell filamentation protein fic


We should revisit this cluster in a few years to see whether or not the truth is hidden as deeply as it appears.

These Conjectures are Valuable, but They are Really Only a By-Product of a Far More Important Advance

In this section, I will present the view that the conjectures that are now emerging (and, there will easily be hundreds of them) are important, but not the really valuable part of what is happening.
To understand the real step forward, we need to think about where we are going. I claim that the next big step in filling in our understanding of unicellular life will be to model microbes as finite-state machines that make transitions between states in response to a changing environment. I believe that some readers will consider my assertion to be obvious and not worth much thought; a second set will consider it silly and obviously counterproductive. To understand the significance of the assertion, it will be necessary to make it completely precise. So, let me try.
Let us specifically consider what I mean in the context of Escherichia coli, the organism that I used in the examples above. The goal will be to go through the following steps:
  1. Define a set of approximate atomic regulons. We have a reasonable starting point with the 483 existing sets of genes. However, this set needs to be substantially extended. At this point 2079 genes have been placed into these putative atomic regulons, and this amounts to less than half of the genes in E.coli. We have made no effort to form a comprehensive set.
  2. Define a small set of states of the cell. Initially, this will probably be very few. This is a somewhat arbitrary process, since the notion of "state" is relatively arbitrary. I believe that we will move towards a basic hierarchy of states. That is, we will have a few large states, each of which contains a number of "substates". There is no question state, as a technical task, this is not difficult. However, to be meaningful the set of states must reflect the same reality skilled microbial physiologists use to organize their thoughts.
  3. Understand the experimental conditions that determine the atomic regulons. To date, we have made no attempt to understand the relationship between experimental conditions and atomic regulons. It may be prohibitively difficult to actually learn anything.
  4. Create plausible metabolic models for each state of the cell. I am more enthusiastic about the use of metabolic modeling. The goal of "Given a set of reactions corresponding to a putative state of the cell (i.e., harvested from the set of atomic regulons that are ON in the state), predict what extra machinery is needed for the cell to function" is the sort of effort that will force merging of atomic regulons and will drag in new machinery absent from the initial model.
  5. Force the remaining genes into approximate atomic regulons. The remaining genes not in atomic regulons can be forced into the initial atomic regulons with the closest expression profiles, or into new atomic regulons based on a notion of "minimal distance" between profiles.
  6. Define the regulatory model. Once the states and atomic regulons have been imposed, the regulatory model can be studied. Clearly, the notion is that we have a limited set of states, and that transitions between states occur. As each transition is proposed and verified, the corresponding regulatory apparatus can be characterized. Much os this is already done for E.coli, but I confess that it is not obvious to me how the set of transitions has been defined. I believe that a great deal is known about the roles of specific regulators, but connecting this body of work with the simplistic view based on atomic regulons will be a substantial amount of work.
By listing some of these steps, I do not mean to say "This is what we will do." I offer them solely as a suggestion of steps we might take; but I do hold the view that taking these simple steps will force a radical advance in the field. By imposing a structured view of the genes, metabolism, and regulation (in terms of "states" and "atomic regulons"), we impose the framework that allows conjectures of the sort we saw in the first section to emerge.

The Pipeline that Needs to be Built

In the last section, I argued that we were progressing towards the goal of defining states of the cell, atomic regulons, and rules governing transitions between states. In this section, I would like to just make some comments about specific projects that should be started.

I would begin by saying that the very limited expression data that we have been able to gather is proving to be extremely useful. We need to get data for more organisms, and we need at least text descriptions of the experimental conditions. I have tried to participate in this process, but it is a tedious, complex process that breaks down in many ways. We need to architect a protocol that will allow us to absorb rapidly growing amounts of data in a form that is useful to us. Since the availability of expression data make skyrocket due to new sequencing capabilities, I would sugest focusing on working with a limited set of groups, forcing minimal consistency, and adding more organisms as large amounts of data become available. For now, let us get a few more genomes, clean up what we have, and try to capture the algorithms used to create the existing data.

The next step must almost certainly be picking a small number of genomes with substantial expression data and push the attempt to form comprehensive and reasonably accurate atomic regulons. I would favor E.coli, Bacillus subtilis, and Shewanella. Good arguments could be made for adding strains of Clostridia, and Salmonella. We should form partnerships in each case.

In each case, a "working set" of atomic regulons should be formed. Then, each experiment should be viewed as a "state" (or, more precisely, as a minor variant of a small set of "states"). That is, it should be possible for the cell to grow under the conditions omost experiments, and for those experiments we should be able to construct a metabolic network that is viable. If we cannot, we have an inconsistency, and these should be systematically removed.

I believe that, if we push 3-5 organisms through to the point where we have a reasonable estimate of states and atomic regulons, it will lead almost immediately to rapid advances in analysis of regulation and clarification of the functions of the remaining "hypothetical genes".