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pmid:26453029
Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A.
Jennifer M H Geddes · Daniel Croll · Mélissa Caza · Nikolay Stoynov · Leonard J Foster · James W Kronstad
BMC microbiology · 2015 doi:10.1186/s12866-015-0532-3
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:26453029", "kind": "science-record", "revision": 6, "content_hash": "sha256:29150767728bf9747dc908a8e9ad1b668319d475cdc4e0c9c1cc830cf973ff7a", "created_at": "2026-11-01T15:40:11Z", "updated_at": "2026-11-01T21:20:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A.", "doi": "10.1186/s12866-015-0532-3", "pmid": "26453029", "authors": ["Jennifer M H Geddes", "Daniel Croll", "Mélissa Caza", "Nikolay Stoynov", "Leonard J Foster", "James W Kronstad"], "journal": "BMC microbiology", "year": 2015, "abstract": "BACKGROUND: The pathogenic yeast Cryptococcus neoformans causes life-threatening meningoencephalitis in individuals suffering from HIV/AIDS. The cyclic-AMP/protein kinase A (PKA) signal transduction pathway regulates the production of extracellular virulence factors in C. neoformans, but the influence of the pathway on the secretome has not been investigated. In this study, we performed quantitative proteomics using galactose-inducible and glucose-repressible expression of the PKA1 gene encoding the catalytic subunit of PKA to identify regulated proteins in the secretome.\nMETHODS: The proteins in the supernatants of cultures of C. neoformans were precipitated and identified using liquid chromatography-coupled tandem mass spectrometry. We also employed multiple reaction monitoring in a targeted approach to identify fungal proteins in samples from macrophages after phagocytosis of C. neoformans cells, as well as from the blood and bronchoalveolar fluid of infected mice.\nRESULTS: We identified 61 secreted proteins and found that changes in PKA1 expression influenced the extracellular abundance of five proteins, including the Cig1 and Aph1 proteins with known roles in virulence. We also observed a change in the secretome profile upon induction of Pka1 from proteins primarily involved in catabolic and metabolic processes to an expanded set that included proteins for translational regulation and the response to stress. We further characterized the secretome data using enrichment analysis and by predicting conventional versus non-conventional secretion. Targeted proteomics of the Pka1-regulated proteins allowed us to identify the secreted proteins in lysates of phagocytic cells containing C. neoformans, and in samples from infected mice. This analysis also revealed that modulation of PKA1 expression influences the intracellular survival of cryptococcal cells upon phagocytosis.\nCONCLUSIONS: Overall, we found that the cAMP/PKA pathway regulates specific components of the secretome including proteins that affect the virulence of C. neoformans. The detection of secreted cryptococcal proteins from infected phagocytic cells and tissue samples suggests their potential utility as biomarkers of infection. The proteomics data are available via ProteomeXchange with identifiers PXD002731 and PASS00736.", "claims": [{"id": "claim-method", "statement": "For the comparative analysis of the end-point samples, the statistical significance of the fold changes of the identified secreted proteins present under both Pka1-repressed and Pka1-induced conditions was evaluated using a Student’s t-test (p-value < 0.05). To confirm the statistically significant Pka1-regulated proteins identified from the end-point analysis, a multiple-hypothesis testing correction was performed on the secretome data using the Benjamini and Hochberg method with a false discovery rate of 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26453029", "locator": "sections[21] \"Protein identification by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and mass spectrometry data analysis\" paragraph 4", "quote": "For the comparative analysis of the end-point samples, the statistical significance of the fold changes of the identified secreted proteins present under both Pka1-repressed and Pka1-induced conditions was evaluated using a Student’s t-test (p-value < 0.05). To confirm the statistically significant Pka1-regulated proteins identified from the end-point analysis, a multiple-hypothesis testing correction was performed on the secretome data using the Benjamini and Hochberg method with a false discovery rate of 0.05."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:26453029"], "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:PXD002731"], "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:PXD002731"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:26453029", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12866-015-0532-3", "sha256": "sha256:96cdc6571f643ba9e54d82009842e0a5a02e9291b117145bb969786700715ec5", "bytes": 104821, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12866-015-0532-3", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC4600298", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD002731", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD002731", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD002731", "version": null, "note": "Availability of supporting dataThe mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium [93] via the PRIDE partner repository [94] with the dataset identifier PXD002731 and the PASSEL partner repository with the dataset identifier PASS00736.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Availability of supporting dataThe mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium [93] via the PRIDE partner repository [94] with the dataset identifier PXD002731 and the PASSEL partner repository with the dataset identifier PASS00736.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A", "resolution_checked_at": "2026-11-01T15:39:58Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:26453029:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:127d70052fd2c771b7d78823f0d7788a4b70107d568ec94dbfcfc8355c082dcb", "bytes": 2513, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Proteins identified in the secretome of C. neoformans collected at 16, 48, 72, and 120 hpi grown in Pka1-repressed (glucose-containing medium) and Pka1-induced (galactose-containing medium) conditions", "structure": {"pmcid": "PMC4600298", "section_index": 3, "section_title": "Control of PKA1 expression results in a change of the protein secretion profile", "row_count": 32, "column_count": 8}, "table": {"label": "Table 1", "caption": "Proteins identified in the secretome of C. neoformans collected at 16, 48, 72, and 120 hpi grown in Pka1-repressed (glucose-containing medium) and Pka1-induced (galactose-containing medium) conditions", "rows": [["GO categoriesa", "Accession number", "Protein Name", "", "Fold changeb*", "Std. 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Dev."], ["Carbohydrate catabolic process"], ["", "CNAG_02189", "α-Amylase", "0.777", "0.019"], ["GTP catabolic process"], ["", "CNAG_06125", "Translation elongation factor 1 α", "2.062", "2.181"], ["Carbohydrate metabolic process"], ["", "CNAG_02860", "Endo-1,3(4)-β-glucanase", "0.947", "0.583"], ["", "CNAG_06501", "1,3-β-glucanosyltransferase", "0.968", "0.100"], ["", "CNAG_05799", "Chitin deacetylase", "1.439", "0.775"], ["", "CNAG_06291", "Deacetylase", "1.464", "0.778"], ["", "CNAG_01239", "Chitin deacetylase", "2.014", "0.584"], ["Cellular carbohydrate metabolic process"], ["", "CNAG_03225", "Malate dehydrogenase", "0.472", "0.546"], ["Pentose-phosphate pathway"], ["", "CNAG_07561", "Phosphogluconate dehydrogenase", ">10", ">10"], ["Protein ubiquitination"], ["", "CNAG_01920", "Polyubiquitin", "1.261", "0.396"], ["ATP hydrolysis coupled proton transport"], ["", "CNAG_05918", "F0F1 ATP synthase subunit β", "0.451", "0.249"], ["", "CNAG_05750", "ATPase α subunit", "0.604", "0.387"], ["Transmembrane transport"], ["", "CNAG_06101", "Eukaryotic ADP/ATP carrier", "7.524", "9.753"], ["Methionine biosynthetic process"], ["", "CNAG_01890", "5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase", "0.778", "0.327"], ["Dephosphorylation"], ["", "CNAG_02944", "Acid phosphatase", "1.862", "0.083"], ["Glycolysis"], ["", "CNAG_03072", "Phosphopyruvate hydratase", "3.093", "3.377"], ["Oxidation-reduction process"], ["", "CNAG_01019", "Cu/Zn superoxide dismutase", "0.302", "0.161"], ["", "CNAG_03465", "Laccase", "0.718", "0.668"], ["Proteolysis"], ["", "CNAG_00919", "Carboxypeptidase D", "4.664", "5.261"], ["Response to stress"], ["", "CNAG_01727", "Hsc70-4", "1.883", "2.094"], ["Translation"], ["", "CNAG_06095", "Ribosomal protein L13", "0.147", "0.057"], ["Unknown/Unclassified"], ["", "CNAG_01653", "Cytokine-inducing glycoprotein", "0.134", "0.158"], ["", "CNAG_00407", "Glyoxal oxidase", "0.719", "0.230"], ["", "CNAG_04291", "Glycosyl-hydrolase", "0.583", "0.287"], ["", "CNAG_02030", "Glyoxal oxidase", "0.513", "0.109"], ["", "CNAG_06267", "Rds1 protein", "3.409", "0.106"], ["Hypothetical"], ["", "CNAG_05312", "Conserved hypothetical protein", "0.341", "0.100"], ["", "CNAG_03007", "Conserved hypothetical protein", "0.518", "0.649"], ["", "CNAG_01562", "Conserved hypothetical protein", "0.942", "0.194"], ["", "CNAG_05893", "Conserved hypothetical protein", "0.991", "0.487"], ["", "CNAG_01047", "Conserved hypothetical protein", "6.714", "6.494"], ["", "CNAG_00588", "Conserved hypothetical protein", ">10", ">10"], ["", "CNAG_03223", "Conserved hypothetical protein", ">10", ">10"], ["", "CNAG_00586", "Conserved hypothetical protein", ">10", ">10"]], "row_count": 52, "column_count": 5, "numeric_cells": 108, "header_rows": 1, "locator": "section[4]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:26453029:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:61fe43962faf342ccbe12440603ddaedca31f9ad7223ef07187b7bc19dcc281f", "bytes": 1924, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[2]#Tab3", "version": null, "note": "Proteins identified in the secretome of C. neoformans collected at 96 hpi from cells grown in Pka1-induced (galactose-containing medium) conditions", "structure": {"pmcid": "PMC4600298", "section_index": 4, "section_title": "Identification of secreted proteins regulated by Pka1", "row_count": 33, "column_count": 5}, "table": {"label": "Table 3", "caption": "Proteins identified in the secretome of C. neoformans collected at 96 hpi from cells grown in Pka1-induced (galactose-containing medium) conditions", "rows": [["GO categoriesa", "Accession number", "Protein name", "Fold changeb", "Std. Dev."], ["Carbohydrate catabolic process", "", ""], ["", "CNAG_02189", "α-Amylase", "1.061", "0.080"], ["GTP catabolic process", "", ""], ["", "CNAG_06125", "Translation elongation factor 1 α", "0.462", "0.555"], ["Carbohydrate metabolic process", "", ""], ["", "CNAG_04245", "Chitinase", "0.621", "0.562"], ["", "CNAG_06501", "1,3-β-glucanosyltransferase", "1.101", "0.140"], ["", "CNAG_01239", "Chitin deacetylase", "2.659", "1.996"], ["", "CNAG_02860", "Endo-1,3(4)-β-glucanase", "3.210", "1.665"], ["Protein ubiquitination", "", ""], ["", "CNAG_01920", "Polyubiquitin", "0.509", "0.501"], ["ATP hydrolysis coupled proton transport", "", ""], ["", "CNAG_05750", "ATPase α subunit", "1.785", "1.765"], ["Dephosphorylation", "", ""], ["", "CNAG_02944", "Acid phosphatase", "0.233", "0.061"], ["Oxidation-reduction process", "", ""], ["", "CNAG_01019", "Cu/Zn superoxide dismutase", "0.350", "0.142"], ["", "CNAG_03465", "Laccase", "1.000", "0.107"], ["Proteolysis", "", ""], ["", "CNAG_00919", "Carboxypeptidase D", "5.770", "3.708"], ["Response to stress", "", ""], ["", "CNAG_01750", "Chaperone", ">10", ">10"], ["Unknown/Unclassified", "", ""], ["", "CNAG_04291", "Glycosyl-hydrolase", "0.989", "0.959"], ["", "CNAG_00407", "Glyoxal oxidase", "1.209", "0.648"], ["", "CNAG_06267", "Rds1 protein", "2.834", "0.518"], ["", "CNAG_01653", "Cytokine-inducing glycoprotein", "2.951", "2.753"], ["", "CNAG_04753", "Lactonohydrolase", ">10", ">10"], ["Hypothetical", "", ""], ["", "CNAG_06109", "Conserved hypothetical protein", "0.463", "0.431"], ["", "CNAG_05893", "Conserved hypothetical protein", "1.062", "0.307"], ["", "CNAG_05312", "Conserved hypothetical protein", "3.737", "2.342"]], "row_count": 33, "column_count": 5, "numeric_cells": 66, "header_rows": 1, "locator": "section[4]/table-wrap[2]#Tab3"}}, {"id": "asset:table:pmid:26453029:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:256ba98575043afac369413565760d51c58955ef5dcd626c10123f5143ef08c4", "bytes": 5718, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[6]/table-wrap[1]#Tab4", "version": null, "note": "Bioinformatic analysis of identified and quantified proteins in the secretome of C. neoformans under Pka1-repressed and Pka1-induced conditions", "structure": {"pmcid": "PMC4600298", "section_index": 6, "section_title": "A bioinformatic analysis of the secretome predicts modes of secretion", "row_count": 83, "column_count": 6}, "table": {"label": "Table 4", "caption": "Bioinformatic analysis of identified and quantified proteins in the secretome of C. neoformans under Pka1-repressed and Pka1-induced conditions", "rows": [["GO categoriesa", "Accession number", "Protein name", "Signal peptideb (position)", "GPI anchorc (position)", "Sample preparation"], ["Carbohydrate catabolic process", "", "", ""], ["", "CNAG_02189", "α-Amylase", "Yes (21/22)", "Yes (C-26)", "EtOH, TCA/acetone"], ["GTP catabolic process", "", "", ""], ["", "CNAG_06125", "Translation elongation factor 1 α", "No", "No", "EtOH, TCA/acetone"], ["", "CNAG_06840", "Translation elongation factor 2", "No", "No", "TCA/acetone"], ["Carbohydrate metabolic process", "", "", ""], ["", "CNAG_00799", "Cellulase", "Yes (22/23)", "No", "TCA/acetone"], ["", "CNAG_01239", "Chitin deacetylase", "Yes (18/19)", "Yes (C-28)", "EtOH, TCA/acetone"], ["", "CNAG_02860", "Endo-1,3(4)-β-glucanase", "Yes (22/23)", "No", "EtOH"], ["", "CNAG_04245", "Chitinase", "Yes (21/22)", "No", "EtOH, TCA/acetone"], ["", "CNAG_05799", "Chitin deacetylase", "Yes (18/19)", "Yes (C-28)", "EtOH"], ["", "CNAG_06291", "Deacetylase", "Yes (19/20)", "No", "EtOH, TCA/acetone"], ["", "CNAG_06313", "Phosphoglucomutase", "No", "No", "TCA/acetone"], ["", "CNAG_06501", "1,3-β-glucanosyltransferase", "Yes (20/21)", "Yes (C-6)", "EtOH, TCA/acetone"], ["Cellular carbohydrate metabolic process", "", "", ""], ["", "CNAG_03225", "Malate dehydrogenase", "No", "No", "EtOH, TCA/acetone"], ["Trehalose metabolic process", "", "", ""], ["", "CNAG_03525", "Trehalase", "Yes (18/19)", "No", "TCA/acetone"], ["Glyoxylate metabolic process", "", "", ""], ["", "CNAG_01137", "Aconitase", "No", "No", "TCA/acetone"], ["Pentose-phosphate pathway", "", "", ""], ["", "CNAG_01984", "Transaldolase", "No", "No", "TCA/acetone"], ["", "CNAG_07561", "Phosphogluconate dehydrogenase", "No", "No", "EtOH"], ["Protein ubiquitination", "", "", ""], ["", "CNAG_01920", "Polyubiquitin", "No", "No", "EtOH"], ["ATP hydrolysis coupled proton transport", "", "", ""], ["", "CNAG_05750", "ATPase α subunit", "No", "No", "EtOH, TCA/acetone"], ["", "CNAG_05918", "F0F1 ATP synthase subunit β", "No", "No", "EtOH"], ["Transmembrane transport", "", "", ""], ["", "CNAG_02974", "Voltage-dependent ion-selective channel", "No", "No", "TCA/acetone"], ["", "CNAG_06101", "Eukaryotic ADP/ATP carrier", "No", "Yes (C-25)", "EtOH, TCA/acetone"], ["Methionine biosynthetic process", "", "", ""], ["", "CNAG_01890", "5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase", "No", "No", "EtOH"], ["Dephosphorylation", "", "", ""], ["", "CNAG_02944", "Acid phosphatase", "Yes (16/17)", "No", "EtOH, TCA/acetone"], ["Glycolysis", "", "", ""], ["", "CNAG_03072", "Phosphopyruvate hydratase", "No", "No", "EtOH, TCA/acetone"], ["", "CNAG_06699", "Glyceraldehyde-3-phosphate dehydrogenase", "No", "No", "TCA/acetone"], ["Oxidation-reduction process", "", "", ""], ["", "CNAG_01019", "Cu/Zn superoxide dismutase", "No", "No", "EtOH"], ["", "CNAG_03465", "Laccase", "Yes (20/21)", "No", "EtOH, TCA/acetone"], ["Proteolysis", "", "", ""], ["", "CNAG_00581", "Endopeptidase", "Yes (19/20)", "No", "TCA/acetone"], ["", "CNAG_00919", "Carboxypeptidase D", "Yes (21/22)", "No", "EtOH, TCA/acetone"], ["Response to stress", "", "", ""], ["", "CNAG_00334", "Heat shock protein", "No", "No", "TCA/acetone"], ["", "CNAG_01727", "Hsc70-4", "No", "No", "EtOH"], ["", "CNAG_01750", "Chaperone", "No", "No", "EtOH, TCA/acetone"], ["", "CNAG_06150", "Heat-shock protein 90", "No", "No", "TCA/acetone"], ["Translation", "", "", ""], ["", "CNAG_04021", "60S ribosomal protein L26", "No", "No", "TCA/acetone"], ["", "CNAG_04114", "40S ribosomal protein S0", "No", "No", "TCA/acetone"], ["", "CNAG_06095", "Ribosomal protein L13", "No", "No", "EtOH"], ["", "CNAG_06605", "Ribosomal protein S2", "No", "No", "TCA/acetone"], ["Regulation of transcription", "", "", ""], ["", "CNAG_00483", "Actin", "No", "No", "TCA/acetone"], ["Nucleosome assembly", "", "", ""], ["", "CNAG_06746", "Histone h2b", "No", "No", "TCA/acetone"], ["Unknown/Unclassified", "", "", ""], ["", "CNAG_00407", "Glyoxal oxidase", "Yes (16/17)", "Yes (C-27)", "EtOH, TCA/acetone"], ["", "CNAG_00776", "Immunoreactive mannoprotein MP88", "Yes (22/23)", "Yes (C-30)", "TCA/acetone"], ["", "CNAG_01653", "Cytokine-inducing glycoprotein", "Yes (19/20)", "No", "EtOH"], ["", "CNAG_02030", "Glyoxal oxidase", "Yes (21/22)", "Yes (C-32)", "EtOH, TCA/acetone"], ["", "CNAG_02850", "Glucan endo-1,3-α-glucosidase agn1", "Yes (21/22)", "Yes (C-26)", "TCA/acetone"], ["", "CNAG_02864", "Predicted protein", "Yes (16/17)", "No", "TCA/acetone"], ["", "CNAG_02943", "Cytoplasmic protein", "No", "No", "TCA/acetone"], ["", "CNAG_04291", "Glycosyl-hydrolase", "Yes (17/18)", "Yes (C-31)", "EtOH"], ["", "CNAG_04753", "Lactonohydrolase", "No", "No", "EtOH, TCA/acetone"], ["", "CNAG_06267", "Rds1 protein", "Yes (20/21)", "Yes", "EtOH, TCA/acetone"], ["Hypothetical", "", "", ""], ["", "CNAG_00586", "Conserved hypothetical protein", "Yes (23/24)", "No", "EtOH, TCA/acetone"], ["", "CNAG_00587", "Conserved hypothetical protein", "Yes (19/20)", "No", "TCA/acetone"], ["", "CNAG_00588", "Conserved hypothetical protein", "Yes (16/17)", "No", "EtOH"], ["", "CNAG_01047", "Conserved hypothetical protein", "Yes (19/20)", "No", "EtOH, TCA/acetone"], ["", "CNAG_01562", "Conserved hypothetical protein", "Yes (18/19)", "No", "EtOH"], ["", "CNAG_03007", "Conserved hypothetical protein", "No", "No", "EtOH"], ["", "CNAG_03223", "Conserved hypothetical protein", "Yes (19/20)", "Yes (C-18)", "EtOH"], ["", "CNAG_03492", "Conserved hypothetical protein", "Yes (19/20)", "No", "TCA/acetone"], ["", "CNAG_05312", "Conserved hypothetical protein", "Yes (19/20)", "Yes (C-19)", "EtOH, TCA/acetone"], ["", "CNAG_05595", "Conserved hypothetical protein", "Yes (18/19)", "Yes (C-29)", "TCA/acetone"], ["", "CNAG_05893", "Conserved hypothetical protein", "Yes (16/17)", "Yes (C-13)", "EtOH, TCA/acetone"], ["", "CNAG_06109", "Conserved hypothetical protein", "No", "No", "EtOH"]], "row_count": 83, "column_count": 6, "numeric_cells": 119, "header_rows": 1, "locator": "section[6]/table-wrap[1]#Tab4"}}], "gaps": ["asset:data:geo:PXD002731 not downloaded", "asset:data:geo:PXD002731 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, 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To confirm the statistically significant Pka1-regulated proteins identified from the end-point analysis, a multiple-hypothesis testing correction was performed on the secretome data using the Benjamini and Hochberg method with a false discovery rate of 0.05."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (Benjamini-Hochberg-corrected Student’s t-test), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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We also employed multiple reaction monitori", "ed. In this study, we performed quantitative proteomics using galactose-inducible and glucose-repres", "versus non-conventional secretion. Targeted proteomics of the Pka1-regulated proteins allowed us to", "tial utility as biomarkers of infection. The proteomics data are available via ProteomeXchange with"], "order_basis": "paper_text_order:515", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["sions (1.0 x 107 cells) was performed. Three mice were selected for the analysis based on establish", "ptococcosis [34–37]. At 48 hpi, the infected mice were euthanized by CO2 inhalation and 1 ml of BAL", "ng (MRM) sample collection from macrophages, mouse bronchoalveolar lavage, and mouse blood The", "crophages, mouse bronchoalveolar lavage, and mouse blood The survival rates of the WT, pka1Δ mu"], "order_basis": "paper_text_order:3901", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["riefly, cells of the J774A.1 macrophage-like cell line were grown to 80 % confluence in Dulbecco’s Modified Ea"], "order_basis": "paper_text_order:4165", "id": "assay:3"}]}