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pmid:23462205
A chemical proteomics approach to profiling the ATP-binding proteome of Mycobacterium tuberculosis.
Lisa M Wolfe · Usha Veeraraghavan · Susan Idicula-Thomas · Stephan Schürer · Krister Wennerberg · Robert Reynolds · Gurdyal S Besra · Karen M Dobos
Molecular & cellular proteomics : MCP · 2013 doi:10.1074/mcp.M112.025635
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Experiment
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Complete file
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The majority of patients harbor the bacterium in a state of metabolic dormancy. New drugs with novel modes of action are needed to target essential metabolic pathways in M. tuberculosis; ATP-competitive enzyme inhibitors are one such class. Previous screening efforts for ATP-competitive enzyme inhibitors identified several classes of lead compounds that demonstrated potent anti-mycobacterial efficacy as well as tolerable levels of toxicity in cell culture. In this report, a probe-based chemoproteomic approach was used to selectively profile the M. tuberculosis ATP-binding proteome in normally growing and hypoxic M. tuberculosis. From these studies, 122 ATP-binding proteins were identified in either metabolic state, and roughly 60% of these are reported to be essential for survival in vitro. These data are available through ProteomeXchange with identifier PXD000141. Protein families vital to the survival of the tubercle bacillus during hypoxia emerged from our studies. Specifically, along with members of the DosR regulon, several proteins involved in energy metabolism (Icl/Rv0468 and Mdh/Rv1240) and lipid biosynthesis (UmaA/Rv0469, DesA1/Rv0824c, and DesA2/Rv1094) were found to be differentially abundant in hypoxic versus normal growing cultures. These pathways represent a subset of proteins that may be relevant therapeutic targets for development of novel ATP-competitive antibiotics.", "claims": [{"id": "claim-method", "statement": "Statistical analysis was performed using Fisher's exact test in the comparison of two groups (i.e. normal-ATP versus hypoxic-ATP or normal-ATP versus normal-ATPγS).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:23462205", "locator": "sections[12] \"Statistical Analysis\" paragraph 2", "quote": "Statistical analysis was performed using Fisher's exact test in the comparison of two groups (i.e. normal-ATP versus hypoxic-ATP or normal-ATP versus normal-ATPγS)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE partner repository (16) with the dataset identifier PXD000141.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:23462205", "locator": "sections[11] \"Criteria for Protein Identification\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE partner repository (16) with the dataset identifier PXD000141."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 122 ATP-binding proteins in normally growing or hypoxic Mycobacterium tuberculosis, approximately 60% of which are essential for survival in vitro; the proteomics data are available through ProteomeXchange under identifier PXD000141.", "kind": "quantitative", "target": {"value": 60.0, "unit": "per cent", "tolerance": null, "source": "From these studies, 122 ATP-binding proteins were identified in either metabolic state, and roughly 60% of these are reported to be essential for survival in vitro. These data are available through ProteomeXchange with identifier PXD000141."}, "evidence": [{"asset": "source:pmid:23462205", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "From these studies, 122 ATP-binding proteins were identified in either metabolic state, and roughly 60% of these are reported to be essential for survival in vitro. These data are available through ProteomeXchange with identifier PXD000141."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 122 ATP-binding proteins in normally growing or hypoxic Mycobacterium tuberculosis, approximately 60% of which are essential for survival in vitro; the proteomics data are available through ProteomeXchange under identifier PXD000141.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:23462205"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD000141"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD000141"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:23462205", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1074/mcp.M112.025635", "sha256": 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precursor, LpqH", "Rv3763", "15 kDa", "(0.0021)", "17", "1", "4.09"], ["Immunogenic protein, Mpt64", "Rv1980c", "25 kDa", "(0.0021)", "17", "1", "4.09"], ["Hypothetical protein", "Rv2319c", "32 kDa", "(0.0021)", "17", "1", "4.09"], ["Aminomethyltransferase, GcvT", "Rv2211c", "40 kDa", "(0.0021)", "17", "1", "4.09"], ["Superoxide dismutase soda", "Rv3846", "23 kDa", "(0.0031)", "16", "1", "4.00"], ["Cysteinyl-tRNA synthetase 1, CysS1", "Rv3580c", "52 kDa", "(0.0031)", "16", "1", "4.00"], ["DNA polymerase I, PolA", "Rv1629", "98 kDa", "(0.0031)", "16", "1", "4.00"], ["Transmembrane serine/threonine-protein kinase E, PknE", "Rv1743", "61 kDa", "(0.0031)", "16", "1", "4.00"], ["Iron-regulated short-chain dehydrogenase/reductase", "Rv3224", "30 kDa", "(0.0006)", "26", "2", "3.70"], ["Fatty-acid-CoA ligase, FadD23", "Rv3826", "63 kDa", "(0.0099)", "13", "1", "3.70"], ["Leucyl-tRNA synthetase, LeuS", "Rv0041", "108 kDa", "(0.0150)", "12", "1", "3.58"], ["Pyridoxamine 5-phosphate oxidase, PdxH", "Rv2607", "25 kDa", "(0.0150)", "12", "1", "3.58"], ["Conserved hypothetical protein", "Rv2624c", "29 kDa", "(0.0002)", "34", "3", "3.50"], ["Aldehyde dehydrogenase", "Rv0458", "55 kDa", "(0.0066)", "19", "2", "3.25"], ["Acetyl-/propionyl-CoA carboxylase α subunit, AccA1", "Rv2501c", "71 kDa", "(0.0001)", "45", "5", "3.17"], ["Fatty-acid-CoA ligase, FadD7", "Rv0119", "55 kDa", "(0.0020)", "27", "3", "3.17"], ["Electron transfer flavoprotein β subunit, FixA", "Rv3029c", "28 kDa", "(0.0020)", "27", "3", "3.17"], ["Fatty-acid-CoA ligase, FadD36", "Rv1193", "50 kDa", "(0.0460)", "9", "1", "3.17"], ["Transferase", "Rv1201c", "33 kDa", "(0.0460)", "9", "1", "3.17"], ["Phosphoribosylamine-glycine ligase, PurD", "Rv0772", "44 kDa", "(0.0028)", "26", "3", "3.12"], ["Pyruvate kinase, PykA", "Rv1617", "51 kDa", "(0.0021)", "31", "4", "2.95"], ["Low molecular weight protein antigen, Cfp2", "Rv2376c", "17 kDa", "(0.0250)", "15", "2", "2.91"], ["Glutamyl-tRNA", "Rv3009c", "55 kDa", "(0.0000)", "83", "12", "2.79"], ["Transmembrane serine/threonine-protein kinase H, PknH", "Rv1266c", "67 kDa", "(0.0036)", "33", "5", "2.72"], ["Conserved alanine-rich protein", "Rv2744c", "29 kDa", "(0.0480)", "13", "2", "2.70"], ["Transmembrane serine/threonine-protein kinase D, PknD", "Rv0931c", "70 kDa", "(0.0005)", "51", "8", "2.67"], ["Conserved hypothetical protein", "Rv2159c", "36 kDa", "(0.0320)", "18", "3", "2.58"], ["ATP-dependent protease ATP-binding subunit, ClpC1", "Rv3596c", "94 kDa", "(0.0000)", "181", "32", "2.50"], ["Glutamine synthetase, GlnA2", "Rv2222c", "50 kDa", "(0.0280)", "22", "4", "2.46"], ["30 S ribosomal protein S1, RpsA", "Rv1630", "53 kDa", "(0.0360)", "21", "4", "2.39"], ["Succinyl-CoA synthetase β chain, SucC", "Rv0951", "41 kDa", "(0.0170)", "40", "9", "2.15"], ["Endopeptidase ATP-binding protein chain B, ClpB", "Rv0384c", "93 kDa", "(0.0003)", "131", "33", "1.99"], ["Glutamine synthetase, GlnA1", "Rv2220", "54 kDa", "(0.0200)", "65", "18", "1.85"], ["10-kDa chaperonin, GroES", "Rv3418c", "11 kDa", "(0.0049)", "136", "41", "1.73"]], "row_count": 39, "column_count": 7, "numeric_cells": 236, "header_rows": 1, "locator": "section[22]/table-wrap[1]#TI"}}, {"id": "asset:table:pmid:23462205:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ad734e78526b48173d39fa0e8c82935ee62b48033a6dfed1a952725d6e6f9cea", "bytes": 2319, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[22]/table-wrap[2]#TII", "version": null, "note": "Proteins with increased abundance during hypoxic growth", "structure": {"pmcid": "PMC3675820", "section_index": 22, "section_title": "Differential Abundance of Proteins in Normoxic (Normal) Versus Hypoxic State Bacteria", "row_count": 23, "column_count": 7}, "table": {"label": "Table II", "caption": "Proteins with increased abundance during hypoxic growth", "rows": [["Identified proteins", "Accession no.", "Molecular mass", "Fisher's exact test (p value)", "Normal NSAa", "Hypoxic NSAF", "Log fold change"], ["Conserved hypothetical protein", "Rv2623", "32 kDa", "(0.0000)", "1", "14", "−3.81"], ["Acyl-(acyl-carrier protein) desaturase, DesA1", "Rv0824c", "39 kDa", "(0.0000)", "1", "12", "−3.58"], ["Hypothetical protein, Acg", "Rv2032", "37 kDa", "(0.0003)", "1", "8", "−3.00"], ["Phosphoribosylaminoimidazole-succinocarboxamide synthase, PurC", "Rv0780", "33 kDa", "(0.0010)", "1", "7", "−2.81"], ["Ketol-acid reductoisomerase, IlvC", "Rv3001c", "36 kDa", "(0.0010)", "1", "7", "−2.81"], ["Acyl-(acyl-carrier protein) desaturase DesA2", "Rv1094", "31 kDa", "(0.0000)", "2", "12", "−2.58"], ["Isocitrate lyase, Icl", "Rv0467", "47 kDa", "(0.0033)", "1", "6", "−2.58"], ["10-kDa culture filtrate antigen, EsxB", "Rv3874", "11 kDa", "(0.0100)", "1", "5", "−2.32"], ["40-kDa secreted l-alanine dehydrogenase, Ald", "Rv2780", "39 kDa", "(0.0000)", "29", "134", "−2.21"], ["Citrate synthase I, GltA2", "Rv0896", "48 kDa", "(0.0320)", "1", "4", "−2.00"], ["DNA gyrase subunit B, GyrB", "Rv0005", "78 kDa", "(0.0320)", "1", "4", "−2.00"], ["Transcription termination factor ρ", "Rv1297", "65 kDa", "(0.0000)", "4", "15", "−1.91"], ["Iron-regulated heparin-binding hemagglutinin, HbhA", "Rv0475", "22 kDa", "(0.0004)", "3", "11", "−1.87"], ["ATP synthase α chain, AtpA", "Rv1308", "59 kDa", "(0.0011)", "4", "11", "−1.46"], ["Macrolide-transport ATP-binding protein ABC transporter", "Rv2477c", "62 kDa", "(0.0005)", "5", "13", "−1.38"], ["6-Phosphofructokinase, PfkA", "Rv3010c", "37 kDa", "(0.0140)", "5", "9", "-0.85"], ["Fatty-acid oxidation protein, FadB", "Rv0860", "76 kDa", "(0.0010)", "10", "17", "−0.77"], ["Heat shock protein, HspX", "Rv2031c", "16 kDa", "(0.0000)", "133", "223", "−0.75"], ["Conserved hypothetical protein", "Rv1738", "11 kDa", "(0.0019)", "10", "16", "−0.68"], ["Bifunctional polyribonucleotide nucleotidyltransferase, GpsI", "Rv2783c", "80 kDa", "(0.0026)", "13", "18", "−0.47"], ["Adenosylhomocysteinase, SahH", "Rv3248c", "54 kDa", "(0.0000)", "45", "53", "−0.24"], ["Iron-regulated aconitate hydratase, Acn", "Rv1475c", "102 kDa", "(0.0490)", "10", "11", "−0.14"]], "row_count": 23, "column_count": 7, "numeric_cells": 135, "header_rows": 1, "locator": "section[22]/table-wrap[2]#TII"}}, {"id": "asset:table:pmid:23462205:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:90129f1fa03099ad985fb3d2171e1157be533c28ffacab7fac909d9e4d0a4534", "bytes": 3517, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[23]/table-wrap[1]#TIII", "version": null, "note": "Competitive and transient binders of desthiobiotin-ATP in hypoxic cultures", "structure": {"pmcid": "PMC3675820", "section_index": 23, "section_title": "ATP Binding Properties of the M. tuberculosis ATPome", "row_count": 37, "column_count": 7}, "table": {"label": "Table III", "caption": "Competitive and transient binders of desthiobiotin-ATP in hypoxic cultures", "rows": [["", "Gene no.", "Molecular mass", "p value", "Avg. NSAF_ATPγSa", "Avg. NSAF_ATPb", "-Fold change"], ["Competitive binders of desthiobiotin-ATP"], ["Fatty-acid oxidation protein, FadB", "Rv0860", "76 kDa", "(0.0039)", "1", "6.33", "6.33"], ["Inosine-5-monophosphate dehydrogenase, GuaB3", "Rv3410c", "39 kDa", "(0.0056)", "1", "6.00", "6.00"], ["Transcription termination factor ρ", "Rv1297", "65 kDa", "(0.0079)", "1", "5.67", "5.67"], ["Macrolide-transport ATP-binding protein, ABC transporter", "Rv2477c", "62 kDa", "(0.0160)", "1", "5.00", "5.00"], ["Endopeptidase ATP-binding protein chain B, ClpB", "Rv0384c", "93 kDa", "(0.0031)", "2.5", "11.67", "4.67"], ["Iron-regulated heparin-binding hemagglutinin, HbhA", "Rv0475", "22 kDa", "(0.0320)", "1", "4.33", "4.33"], ["Adenosylhomocysteinase, SahH", "Rv3248c", "54 kDa", "(0.0065)", "5.5", "18.33", "3.33"], ["Chaperone protein, DnaK", "Rv0350", "67 kDa", "(0.0001)", "16", "50.00", "3.13"], ["Adenylate kinase, Adk", "Rv0733", "20 kDa", "(0.0400)", "8", "20.33", "2.54"], ["Acyl-(acyl-carrier protein) desaturase, DesA1c", "Rv0824c", "39 kDa", "(0.2200)", "2", "4.67", "2.33"], ["ATP synthase β chain, AtpDc", "Rv1310", "53 kDa", "(0.1500)", "5", "11.33", "2.27"], ["Bifunctional acetyl-/propionyl-coenzyme A carboxylase α chain, AccA3c", "Rv3285", "64 kDa", "(0.2600)", "3", "6.33", "2.11"], ["Transient binders of desthiobiotn-ATP", ""], ["50 S ribosomal protein L7/L12, RplL", "Rv0652", "13 kDa", "(0.3100)", "4.5", "8.67", "1.93"], ["10-kDa chaperonin, GroES", "Rv3418c", "11 kDa", "(0.3600)", "8", "14.33", "1.79"], ["ATP-dependent protease ATP-binding subunit, ClpC1", "Rv3596c", "94 kDa", "(0.5000)", "7", "11.33", "1.62"], ["60-kDa chaperonin 1, GroEL1", "Rv3417c", "56 kDa", "(0.5100)", "3.5", "5.67", "1.62"], ["Conserved hypothetical protein", "Rv2623", "32 kDa", "(0.5600)", "3.5", "5.33", "1.52"], ["40-kDa secreted l-alanine dehydrogenase, Ald", "Rv2780", "39 kDa", "(0.0520)", "36", "45.33", "1.26"], ["Cold shock protein A, CspA", "Rv3648c", "7 kDa", "(0.4400)", "4", "5.00", "1.25"], ["60-kDa chaperonin 2, GroEL2", "Rv0440", "57 kDa", "(0.0000)", "135", "168.67", "1.25"], ["Heat shock protein, HspX", "Rv2031c", "16 kDa", "(0.0002)", "67.5", "75.00", "1.11"], ["Transmembrane serine/threonine-protein kinase A, PknA", "Rv0015c", "46 kDa", "(0.3100)", "4", "4.33", "1.08"], ["Isocitrate lyase, Icl", "Rv0467", "47 kDa", "(0.4300)", "2.5", "2.67", "1.07"], ["Integration host factor, MihF", "Rv1388", "21 kDa", "(0.0280)", "19", "20.00", "1.05"], ["6-Phosphofructokinase, PfkA", "Rv3010c", "37 kDa", "(0.3200)", "3.5", "3.67", "1.05"], ["Bifunctional polyribonucleotide nucleotidyltransferase, GpsI", "Rv2783c", "80 kDa", "(0.1600)", "6.5", "6.67", "1.03"], ["Iron-regulated elongation factor tu tuf", "Rv0685", "44 kDa", "(0.0120)", "20.5", "20.33", "0.99"], ["Propionyl-CoA carboxylase β chain 5, AccD5", "Rv3280", "59 kDa", "(0.5000)", "1.5", "1.33", "0.89"], ["Conserved hypothetical protein", "Rv3269", "10 kDa", "(0.1600)", "4.5", "4.00", "0.89"], ["Electron transfer flavoprotein β subunit, FixA", "Rv3029c", "28 kDa", "(0.3300)", "2", "1.67", "0.83"], ["Conserved hypothetical protein", "Rv1738", "11 kDa", "(0.0390)", "7.5", "6.00", "0.80"], ["Iron-regulated conserved hypothetical protein", "Rv1636", "15 kDa", "(0.0093)", "10", "7.33", "0.73"], ["Transmembrane serine/threonine-protein kinase D, PknD", "Rv0931c", "70 kDa", "(0.0100)", "6", "3.33", "0.56"], ["Conserved hypothetical protein", "Rv3127", "39 kDa", "(0.0640)", "3", "1.67", "0.56"]], "row_count": 37, "column_count": 7, "numeric_cells": 212, "header_rows": 1, "locator": "section[23]/table-wrap[1]#TIII"}}, {"id": "asset:table:pmid:23462205:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3332bd36f3a2aeddeb695e8f72648fb43d8dd0649e1d25f3513888ed645f80f7", "bytes": 9305, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[23]/table-wrap[2]#TIV", "version": null, "note": "Competitive and transient binders of desthiobiotin-ATP in normal cultures", "structure": {"pmcid": "PMC3675820", "section_index": 23, "section_title": "ATP Binding Properties of the M. tuberculosis ATPome", "row_count": 101, "column_count": 7}, "table": {"label": "Table IV", "caption": "Competitive and transient binders of desthiobiotin-ATP in normal cultures", "rows": [["", "Gene no.", "Molecular mass", "p value", "Avg. NSAF_ATPγSa", "Avg. NSAF_ATPb", "Fold change"], ["Competitive Binders of Desthiobiotin-ATP", "", "", "", "", "", ""], ["Acetyl-/propionyl-CoA carboxylase α subunit, AccA1", "Rv2501c", "71 kDa", "(0.0000)", "1.00", "15.67", "15.67"], ["Glutamyl-tRNA amidotransferase subunit B, GatB", "Rv3009c", "55 kDa", "(0.0000)", "2.33", "28.33", "12.14"], ["Inosine-5-monophosphate dehydrogenase, GuaB3", "Rv3410c", "39 kDa", "(0.0000)", "1.00", "11.67", "11.67"], ["Transmembrane serine/threonine-protein kinase H, PknH", "Rv1266c", "67 kDa", "(0.0000)", "1.00", "11.33", "11.33"], ["Fatty-acid-CoA ligase, FadD7", "Rv0119", "55 kDa", "(0.0000)", "1.00", "9.67", "9.67"], ["Phosphoribosylamine-glycine ligase, PurD", "Rv0772", "44 kDa", "(0.0000)", "1.00", "9.33", "9.33"], ["Tryptophanyl-tRNA synthetase, TrpS", "Rv3336c", "36 kDa", "(0.0001)", "1.00", "7.00", "7.00"], ["Polyphosphate kinase, Ppk", "Rv2984", "83 kDa", "(0.0000)", "3.33", "22.67", "6.80"], ["Phosphoglycerate kinase, Pgk", "Rv1437", "43 kDa", "(0.0000)", "3.00", "19.67", "6.56"], ["Cysteinyl-tRNA synthetase 1, CysS1", "Rv3580c", "52 kDa", "(0.0005)", "1.00", "5.67", "5.67"], ["Fatty-acid-CoA ligase, FadD23", "Rv3826", "63 kDa", "(0.0014)", "1.00", "5.00", "5.00"], ["Universal stress protein", "Rv2319c", "32 kDa", "(0.0012)", "1.33", "6.33", "4.75"], ["CTP synthase, PyrG", "Rv1699", "64 kDa", "(0.0024)", "1.00", "4.67", "4.67"], ["Phosphofructokinase, PfkB", "Rv2029c", "35 kDa", "(0.0073)", "1.00", "4.00", "4.00"], ["ATP-dependent protease ATP-binding subunit, ClpC1", "Rv3596c", "94 kDa", "(0.0000)", "15.33", "61.00", "3.98"], ["Anchored-membrane serine/threonine-protein kinase, PknF", "Rv1746", "51 kDa", "(0.0130)", "1.00", "3.67", "3.67"], ["Chaperone protein, HtpG", "Rv2299c", "73 kDa", "(0.0130)", "1.00", "3.67", "3.67"], ["DNA polymerase I, PolA", "Rv1629", "98 kDa", "(0.0078)", "1.67", "6.00", "3.60"], ["Acetate kinase, AckA", "Rv0409", "41 kDa", "(0.0220)", "1.00", "3.33", "3.33"], ["UDP-N-acetylmuramoylalanyl-d-glutamyl-2,6-diaminopimelate-d-alanyl-d-alanyl ligase, MurF", "Rv2157c", "52 kDa", "(0.0220)", "1.00", "3.33", "3.33"], ["Conserved hypothetical protein", "Rv3282", "23 kDa", "(0.0220)", "1.00", "3.33", "3.33"], ["Conserved hypothetical protein", "Rv2510c", "57 kDa", "(0.0220)", "1.00", "3.33", "3.33"], ["Fatty-acid-CoA ligase, FadD28", "Rv2941", "63 kDa", "(0.0077)", "2.33", "7.67", "3.29"], ["Nucleoside diphosphate kinase, NdkA", "Rv2445c", "15 kDa", "(0.0150)", "2.00", "6.33", "3.17"], ["40-kDa secreted l-alanine dehydrogenase, Ald", "Rv2780", "39 kDa", "(0.0066)", "3.00", "9.33", "3.11"], ["Adenosylhomocysteinase, SahH", "Rv3248c", "54 kDa", "(0.0017)", "5.00", "15.00", "3.00"], ["Pyruvate kinase, PykA", "Rv1617", "51 kDa", "(0.0053)", "3.67", "11.00", "3.00"], ["Malate synthase G, GlcB", "Rv1837c", "80 kDa", "(0.0420)", "1.67", "4.67", "2.80"], ["Aldehyde dehydrogenase", "Rv0458", "55 kDa", "(0.0350)", "2.67", "7.00", "2.63"], ["Adenylate kinase, Adk", "Rv0733", "20 kDa", "(0.0035)", "17.33", "36.67", "2.12"], ["transmembrane serine/threonine-protein kinase D, PknD", "Rv0931c", "70 kDa", "(0.0400)", "8.67", "17.67", "2.04"], ["ATP synthase β chain, AtpD", "Rv1310", "53 kDa", "(0.0250)", "13.33", "26.33", "1.98"], ["Transient binders of desthiobiotin-ATP"], ["Endopeptidase ATP-binding protein chain B, ClpB", "Rv0384c", "93 kDa", "(0.0410)", "25.33", "44.33", "1.75"], ["3-Hydroxyacyl-thioester dehydrogenase, HtdY", "Rv3389c", "30 kDa", "(0.4000)", "4.67", "7.00", "1.50"], ["Iron-regulated short-chain dehydrogenase/reductase", "Rv3224", "30 kDa", "(0.4100)", "6.33", "9.33", "1.47"], ["Aminomethyltransferase, GcvT", "Rv2211c", "40 kDa", "(0.4300)", "4.33", "6.33", "1.46"], ["Phosphopantetheine adenylyltransferase, KdtB", "Rv2965c", "18 kDa", "(0.4700)", "2.33", "3.33", "1.43"], ["Chaperone protein, DnaK", "Rv0350", "67 kDa", "(0.3800)", "40.00", "57.00", "1.43"], ["Cold shock protein A, CspA", "Rv3648c", "7 kDa", "(0.5300)", "5.67", "7.67", "1.35"], ["Secreted fibronectin-binding protein antigen", "85-B fbpB", "Rv1886c", "35 kDa", "(0.5400)", "2.00", "2.67"], ["Iron-regulated peptidyl-prolyl cis-trans isomerase, PpiA", "Rv0009", "19 kDa", "(0.5400)", "3.00", "4.00", "1.33"], ["Glutamine synthetase, GlnA2", "Rv2222c", "50 kDa", "(0.5500)", "6.00", "8.00", "1.33"], ["Pyruvate dehydrogenase E2 component, SucB", "Rv2215", "57 kDa", "(0.5500)", "7.33", "9.67", "1.32"], ["Acyl-CoA dehydrogenase, FadE5", "Rv0244c", "66 kDa", "(0.5700)", "3.33", "4.33", "1.30"], ["Pyruvate dehydrogenase E1 component, AceE", "Rv2241", "100 kDa", "(0.5700)", "4.67", "6.00", "1.29"], ["60-kDa chaperonin 2, GroEL2", "Rv0440", "57 kDa", "(0.0180)", "279.00", "352.00", "1.26"], ["Iron-regulated conserved hypothetical protein", "Rv1636", "15 kDa", "(0.3500)", "17.00", "21.00", "1.24"], ["Propionyl-CoA carboxylase β chain 5, AccD5", "Rv3280", "59 kDa", "(0.5800)", "3.00", "3.67", "1.22"], ["Low molecular weight protein antigen, Cfp2", "Rv2376c", "17 kDa", "(0.5000)", "4.67", "5.67", "1.21"], ["Glutamine synthetase, GlnA1", "Rv2220", "54 kDa", "(0.3000)", "17.67", "21.33", "1.21"], ["Heat shock protein, HspX", "Rv2031c", "16 kDa", "(0.1800)", "36.00", "43.33", "1.20"], ["Succinyl-CoA synthetase β chain, SucC", "Rv0951", "41 kDa", "(0.3500)", "11.67", "14.00", "1.20"], ["Oligoribonuclease, Orn", "Rv2511", "23 kDa", "(0.4800)", "5.00", "6.00", "1.20"], ["Protein transport protei, SecE2", "Rv0379", "8 kDa", "(0.5400)", "3.33", "4.00", "1.20"], ["l-Lactate dehydrogenase, LldD2", "Rv1872c", "45 kDa", "(0.4500)", "5.33", "6.33", "1.19"], ["Conserved hypothetical protein", "Rv2159c", "36 kDa", "(0.4300)", "5.67", "6.67", "1.18"], ["Bifunctional coenzyme A carboxylase α chain, AccA3", "Rv3285", "64 kDa", "(0.2800)", "13.67", "16.00", "1.17"], ["50 S ribosomal protein L7/L12, RplL", "Rv0652", "13 kDa", "(0.2500)", "16.00", "18.67", "1.17"], ["Conserved hypothetical protein", "Rv3269", "10 kDa", "(0.4800)", "4.00", "4.67", "1.17"], ["Ribosome recycling factor, Frr", "Rv2882c", "21 kDa", "(0.5700)", "2.33", "2.67", "1.14"], ["Superoxide dismutase, SodA", "Rv3846", "23 kDa", "(0.3900)", "5.33", "6.00", "1.13"], ["Transmembrane serine/threonine-protein kinase E, PknE", "Rv1743", "61 kDa", "(0.3900)", "5.33", "6.00", "1.13"], ["Two-component system transcriptional regulator, DevR", "Rv3133c", "23 kDa", "(0.4600)", "3.33", "3.67", "1.10"], ["Tetrahydrodipicolinate N-succinyltransferase", "Rv1201c", "33 kDa", "(0.4600)", "3.33", "3.67", "1.10"], ["Leucyl-tRNA synthetase, LeuS", "Rv0041", "108 kDa", "(0.3800)", "4.33", "4.67", "1.08"], ["Iron-regulated elongation factor tu tuf", "Rv0685", "44 kDa", "(0.0300)", "40.33", "43.33", "1.07"], ["Immunogenic protein, Mpt64", "Rv1980c", "25 kDa", "(0.3000)", "6.00", "6.33", "1.06"], ["30 S ribosomal protein S1, RpsA", "Rv1630", "53 kDa", "(0.2500)", "7.33", "7.67", "1.05"], ["Transmembrane serine/threonine-protein kinase A, PknA", "Rv0015c", "46 kDa", "(0.2100)", "8.67", "9.00", "1.04"], ["Transcriptional regulator", "Rv0023", "27 kDa", "(0.5600)", "1.67", "1.67", "1.00"], ["Hypothetical protein, Wag31", "Rv2145c", "28 kDa", "(0.4200)", "2.67", "2.67", "1.00"], ["Hypothetical protein", "Rv3818", "58 kDa", "(0.5000)", "2.00", "2.00", "1.00"], ["Conserved alanine-rich protein", "Rv2744c", "29 kDa", "(0.2800)", "5.00", "5.00", "1.00"], ["Enoyl-CoA hydratase, EchA9", "Rv1071c", "36 kDa", "(0.3900)", "3.00", "3.00", "1.00"], ["Conserved hypothetical protein", "Rv2140c", "19 kDa", "(0.5000)", "2.00", "2.00", "1.00"], ["Thiosulfate sulfurtransferase, CysA2", "Rv0815c", "31 kDa", "(0.5600)", "1.67", "1.67", "1.00"], ["Zinc-type alcohol dehydrogenase NAD-dependent, AdhB", "Rv0761c", "40 kDa", "(0.2300)", "4.67", "4.33", "0.93"], ["Transcriptional regulator, MoxR1", "Rv1479", "41 kDa", "(0.2800)", "3.33", "3.00", "0.90"], ["60-kDa chaperonin 1, GroEL1", "Rv3417c", "56 kDa", "(0.0270)", "16.33", "14.67", "0.90"], ["Meromycolate extension acyl carrier protein, AcpM", "Rv2244", "13 kDa", "(0.1400)", "6.33", "5.67", "0.89"], ["Haloalkane dehalogenase", "Rv2296", "33 kDa", "(0.1500)", "6.00", "5.33", "0.89"], ["Succinyl-CoA synthetase α chain, SucD", "Rv0952", "31 kDa", "(0.1600)", "5.67", "5.00", "0.88"], ["ATP synthase α chain, AtpA", "Rv1308", "59 kDa", "(0.3300)", "2.33", "2.00", "0.86"], ["Integration host factor, MihF", "Rv1388", "21 kDa", "(0.0001)", "41.33", "34.67", "0.84"], ["acyl-CoA dehydrogenase, FadE25", "Rv3274c", "42 kDa", "(0.3500)", "2.00", "1.67", "0.83"], ["DNA polymerase III β chain, DnaN", "Rv0002", "42 kDa", "(0.3500)", "2.00", "1.67", ""], ["Pyridoxamine 5-phosphate oxidase, PdxH", "Rv2607", "25 kDa", "(0.1100)", "5.67", "4.67", "0.82"], ["10-kDa chaperonin, GroES", "Rv3418c", "11 kDa", "(0.0000)", "50.33", "40.67", "0.81"], ["Iron-regulated aconitate hydratase, Acn", "Rv1475c", "102 kDa", "(0.1200)", "5.00", "4.00", "0.80"], ["30 S ribosomal protein S16, RpsP", "Rv2909c", "17 kDa", "(0.3800)", "1.67", "1.33", "0.80"], ["Hypothetical protein, Cfp17", "Rv1827", "17 kDa", "(0.2000)", "3.33", "2.67", "0.80"], ["Fructose-bisphosphate aldolase, Fba", "Rv0363c", "37 kDa", "(0.2000)", "3.00", "2.33", "0.78"], ["Short-chain type dehydrogenase/reductase", "Rv0148", "30 kDa", "(0.2000)", "3.00", "2.33", "0.78"], ["Transcriptional regulator, TetR family", "Rv0144", "31 kDa", "(0.2000)", "3.00", "2.33", "0.78"], ["19-kDa lipoprotein antigen precursor, LpqH", "Rv3763", "15 kDa", "(0.0250)", "8.67", "6.33", "0.73"], ["Conserved hypothetical protein", "Rv2406c", "15 kDa", "(0.2100)", "2.33", "1.67", "0.71"], ["Electron transfer flavoprotein β subunit, FixA", "Rv3029c", "28 kDa", "(0.0039)", "13.67", "9.67", "0.71"], ["Enolase, Eno", "Rv1023", "45 kDa", "(0.1300)", "3.33", "2.33", "0.70"]], "row_count": 101, "column_count": 7, "numeric_cells": 607, "header_rows": 1, "locator": "section[23]/table-wrap[2]#TIV"}}], "gaps": ["asset:data:geo:PXD000141 not downloaded", "asset:data:geo:PXD000141 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "contingency_analysis", "specific": "fisher_exact", "label": "Categorical (contingency table) analysis", "dsl_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Statistical analysis was performed using Fisher's exact test in the comparison of two groups (i.e. normal-ATP versus hypoxic-ATP or normal-ATP versus normal-ATPγS)."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 60.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: fisher_exact."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PXD000141"], "resolved_accessions": ["PXD000141"], "statements": ["The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE partner repository (16) with the dataset identifier PXD000141."], "basis": "The paper names PXD000141 in ProteomeXchange Consortium and the accession resolves in the repository. 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