{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Tabular":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/report.pr_matrix.tsv","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/report.pg_matrix.tsv"],"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR03F.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASR03.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR04R.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR01F.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASF01.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASF03.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASR01.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR04F.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR03R.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR01R.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR02F.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR05F.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASF02.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR05R.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASR02.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/ASPR02R.raw"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349/report.parquet"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["mm.parbhu@manipal.edu"],"submitter":["Abhibroto Karmakar"],"technology_type":["Mass Spectrometry","Bottom-up proteomics"],"software":[""],"submitter_keywords":["Explainable ai (xai)","Biomarker","Precision medicine","Shap values","Cytokine","Machine learning","Proteomics","Multi-omics"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD075349"],"tissue":["Blood Plasma"],"sample_protocol":["Thermo High Select Top14 depletion column were used to process 10ul serum samples for protein depletion as per manufacturer protocol. For digestion, depleted protein samples were reduced with 5 mM TCEP, and further alkylated with 50 mM iodoacetamide, and digested for 16 hours at 37 °C using Trypsin (1:50, Trypsin/lysate ratio). The peptides were further cleaned using a C18 silica cartridge, and dried using speed vac device. The dried peptides were resuspended in buffer A (2% acetonitrile, 0.1% formic acid) and frozen till further analysis."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["All samples were processed and RAW files generated were analyzed with DIA-NN 2.2.0 software against the Uniprot Human database containing 26,575 protein entries. The protease used to generate peptides, i.e. enzyme specificity was set for trypsin/P (cleavage at the C terminus of “K/R: unless followed by “P”). Carbamidomethyl on cysteine as fixed modification and oxidation of methionine and N-terminal acetylation were considered as variable modifications for database search. Both peptide spectrum match and protein false discovery rate were set to 0.01 FDR."],"omics_type":["Proteomics"],"labhead":["Dr. Mukhyaprana M Prabhu"],"instrument_platform":[""],"labhead_affiliation":["Department of General Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["abhibroto.karmakar@learner.manipal.edu"],"publication":["42317313 Karmakar A, Mishra S, Kumar U, Kamath R, Ravindran V, Suryakanth VB, Prabhu S, Nagaraju SP, Prabhu MM, Karmakar S. Integrative plasma proteomics and myeloid- interferon profiling reveal an AI-validated vascular- endothelial stress signature distinguishing SLE flare from remission in an Indian cohort a discovery - phase study. Front Immunol. 2026 17:1819049 10.3389/fimmu.2026.1819049"],"submitter_affiliation":["Department of General Medicine, Kasturba Medical College,Manipal, Manipal Academy of Higher Education, India"],"submitter_country":["India"],"pubmed_abstract":["<h4>Background</h4>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by unpredictable flares and variable clinical quiescence. Despite validated clinical indices like the British Isles Lupus Assessment Group (BILAG) score, reliable molecular biomarkers for monitoring disease activity remain limited, particularly in underrepresented South Asian populations. Weaimed to identify arobust molecular framework to distinguish SLE flares from remission in an Indian cohort.<h4>Methods</h4>We conducted a discovery-phase study in an Indian cohort (n=16) stratified by Easy-BILAG scoring. Plasma proteomic profiling via LC-MS/MS was integrated with targeted cytokine quantification using the Olink Proximity Extension Assay (PEA). Differential expression and network analyses delineated immune-regulatory, hypoxic-vascular, and myeloid-activation pathways. A Random Forest classifier was trained on selected biomarkers and evaluated using leave-one-out cross-validation (LOOCV), permutation testing, and bootstrapped AUROC confidence intervals, with model interpretability assessed by SHAP values. Data are available via ProteomeXchange with identifier PXD075349.<h4>Results</h4>Proteomic comparison identified a compact panel of proteins distinguishing flare from remission, characterized by a molecular polarization; flare states exhibited upregulation of COL18A1 and CSF1 (vascular and myeloid activation), while remission showed sustained expression of cytoskeletal scaffolding and immunoregulatory components, including FLNA, SH3BGRL3, and IGHG4. Cytokine analyses identified coordinated chemokine modules (CXCL9, CCL2, CCL3, and CCL13) preferentially upregulated during flare. The machine-learning model achieved robust internal discrimination with a mean AUROC of 0.96. Notably, a COL18A1 normalized protein expression cut-off yielded 100% specificity and 87.5% sensitivity, acting as an objective 'rule-in' adjunct for active disease. Normalized protein expression (NPX) cut-off yielded 100% specificity and 87.5% sensitivity, acting as an objective \"rule-in\" adjunct for active disease.<h4>Conclusions</h4>This study establishes a parsimonious 5-protein biosignature of candidate leads (COL18A1, HYOU1, IGHG4, FLNA, and SH3BGRL3) that effectively captures the multifactorial pathophysiology of SLE flare. By anchoring discovery in a systematically under sampled Indian population, this work enhances global diversity in lupus biomarker research and establishes a scalable, AI-driven framework for precision assessment of disease activity."],"pubmed_title":["Integrative plasma proteomics and myeloid- interferon profiling reveal an AI-validated vascular- endothelial stress signature distinguishing SLE flare from remission in an Indian cohort a discovery - phase study."],"pubmed_authors":["Karmakar Abhibroto A, Mishra Santanu S, Kumar Uma U, Kamath Rachana R, Ravindran Vinod V, Suryakanth Varashree Bolar VB, Prabhu Smitha S, Nagaraju Shankar Prasad SP, Prabhu Mukhyaprana M MM, Karmakar Subhradip S"],"additional_accession":[]},"is_claimable":false,"name":"Integrative Plasma Proteomics and Myeloid-Interferon Profiling Reveal an AI-Validated Vascular-Endothelial Stress Signature Distinguishing SLE Flare from Remission in an Indian Cohort A Discovery – Phase Study","description":"Background: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by unpredictable flares and variable clinical quiescence. Despite validated clinical indices like the British Isles Lupus Assessment Group (BILAG) score, reliable molecular biomarkers for monitoring disease activity remain limited, particularly in underrepresented South Asian populations. We aimed to identify a robust molecular framework to distinguish SLE flares from remission in an Indian cohort. Methods: We conducted a discovery-phase study in an Indian cohort (n=16) stratified by Easy-BILAG scoring. Plasma proteomic profiling via LC-MS/MS was integrated with targeted cytokine quantification using the Olink Proximity Extension Assay (PEA). Differential expression and network analyses delineated immune-regulatory, hypoxic-vascular, and myeloid-activation pathways. A Random Forest classifier was trained on selected biomarkers and evaluated using leave-one-out cross-validation (LOOCV), permutation testing, and bootstrapped AUROC confidence intervals, with model interpretability assessed by SHAP values. Results: Proteomic comparison identified a compact panel of proteins distinguishing flare from remission, characterized by a molecular polarization; flare states exhibited upregulation of COL18A1 and CSF1 (vascular and myeloid activation), while remission showed sustained expression of cytoskeletal scaffolding and immunoregulatory components, including FLNA, SH3BGRL3, and IGHG4. Cytokine analyses identified coordinated chemokine modules (CXCL9, CCL2, CCL3, and CCL13) preferentially upregulated during flare. The machine-learning model achieved robust internal discrimination with a mean AUROC of 0.96. Notably, a COL18A1 normalized protein expression cut-off yielded 100% specificity and 87.5% sensitivity, acting as an objective 'rule-in' adjunct for active disease. (NPX) cut-off yielded 100% specificity and 87.5% sensitivity, acting as an objective \"rule-in\" adjunct for active disease. Conclusions: This study establishes a parsimonious 5-protein biosignature (COL18A1, HYOU1, IGHG4, FLNA, and SH3BGRL3) that effectively captures the multifactorial pathophysiology of SLE flare. By anchoring discovery in a systematically under sampled Indian population, this work enhances global diversity in lupus biomarker research and establishes a scalable, AI-driven framework for precision assessment of disease activity.","dates":{"publication":"2026-06-22","submission":"2026-03-07"},"accession":"PXD075349","cross_references":{"TAXONOMY":["NEWT:6945","NEWT:3555","NEWT:2","NEWT:157546","NEWT:35554","NEWT:38942","NEWT:307972","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:45351","NEWT:43179","NEWT:4513","NEWT:5722","NEWT:376741","NEWT:55153","NCBITaxon:10407","NEWT:1736309","NEWT:309800","NEWT:1211601","NEWT:876138","NEWT:237561","NEWT:5833","NEWT:6928","NEWT:10036","NEWT:36745","NEWT:1351","NEWT:1438992","NEWT:2649997","NEWT:272563","NEWT:224326","NCBITaxon:79857","NEWT:1096976","NEWT:95648","NEWT:3885","NEWT:3888","NEWT:1589","NEWT:135622","NEWT:6915","NEWT:3649","NEWT:101510","NEWT:3880","NEWT:272559","NEWT:3641","NEWT:383379","NEWT:466585","NEWT:10029","NEWT:1000589","NEWT:85963","NEWT:85962","NEWT:317447","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:398580","NEWT:4565","NEWT:1264690","NEWT:515619","NEWT:192875","NEWT:34305","NEWT:59729","NCBITaxon:183674","NEWT:224308","NEWT:84645","NEWT:626528","NEWT:139927","NEWT:4558","NEWT:209285","NEWT:1283","NEWT:931281","NEWT:4550","NEWT:1000561","NEWT:197","NCBITaxon:79824","NEWT:4787","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:3218","NEWT:5759","NEWT:1736231","NEWT:1270","NEWT:2242","NEWT:4784","NEWT:11320","NEWT:360106","NEWT:286","NEWT:287","NEWT:10117","NEWT:10239","NEWT:10116","NEWT:1280","NEWT:1735272","NEWT:83334","NEWT:83332","NEWT:44685","NEWT:317513","NEWT:1148","NEWT:580240","NEWT:294128","NEWT:11676","NEWT:55571","NEWT:100226","NEWT:4530","NEWT:4896","NEWT:75058","NEWT:13616","NEWT:1094343","NEWT:296543","NEWT:1773","NEWT:1895","NEWT:1182590","NEWT:3712","NEWT:935293","NEWT:64152","NEWT:4924","NEWT:749200","NEWT:990346","NEWT:145953","NEWT:257309","NEWT:100816","NEWT:263","NEWT:230741","NEWT:52283","NEWT:284812","NCBITaxon:1313","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44544","NEWT:4911","NEWT:645463","NEWT:3702","NEWT:129249","NEWT:243277","NEWT:990119","NEWT:408172","NEWT:408170","NEWT:493760","NEWT:260710","NEWT:257313","NEWT:400772","NEWT:3708","NEWT:128161","NEWT:332648","NEWT:106592","NEWT:536231","NEWT:460519","NEWT:1187947","NEWT:1432138","NEWT:10312","NEWT:1424507","NCBITaxon:1773","NEWT:9598","NEWT:8030","NEWT:1639","NEWT:188229","NEWT:3818","NEWT:480","NEWT:4909","NEWT:67767","NEWT:432359","NEWT:46835","NEWT:1182263","NEWT:2711","NEWT:376686","NEWT:95486","NEWT:9103","NEWT:29159","NEWT:253","NEWT:10306","NCBITaxon:2759","NEWT:1233435","NEWT:8022","NEWT:145943","NCBITaxon:4932","NEWT:595536","NEWT:240906","NEWT:593117","NEWT:3635","NEWT:5811","NEWT:235443","NEWT:272624","NEWT:411483","NEWT:884019","NEWT:198215","NEWT:411490","NEWT:983964","NEWT:169963","NEWT:32644","NEWT:499175","NEWT:109779","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:367830","NEWT:1255228","NEWT:178616","NEWT:410289","NEWT:373153","NEWT:352472","NEWT:357","NEWT:360094","NEWT:470","NEWT:1313","NEWT:411469","NEWT:84023","NEWT:559292","NEWT:39491","NCBITaxon:5811","NEWT:411464","NEWT:411460","NEWT:2014887","NEWT:2762","NEWT:1174673","NEWT:562","NEWT:411470","NEWT:33952","NEWT:2094720","NCBITaxon:2697049","NEWT:571256","NEWT:28038","NEWT:1663","NEWT:1423","NEWT:4932","NEWT:3603","NEWT:2759","NEWT:3847","NEWT:327159","NEWT:178876","NEWT:327160","NEWT:573","NEWT:9031","NEWT:7091","NEWT:241368","NEWT:42528","NEWT:190802","NEWT:9778","NEWT:150475","NEWT:303","NEWT:9417","NEWT:7111","NEWT:347515","NEWT:1216979","NEWT:5180","NEWT:256737","NEWT:115104","NEWT:1121114","NEWT:663","NEWT:1081927","NEWT:1238993","NEWT:67825","NEWT:185579","NEWT:941442","NEWT:220668","NEWT:13076","NEWT:1249668","NEWT:7108","NEWT:317","NEWT:7227","NEWT:7469","NEWT:885318","NEWT:9402","NEWT:415540","NEWT:550","NEWT:675060","NEWT:4081","NEWT:334542","NEWT:554","NEWT:98334","NEWT:426428","NEWT:7574","NEWT:1715256","NEWT:7215","NEWT:575412","NEWT:29204","NEWT:2172103","NEWT:507601","NEWT:643680","NCBITaxon:6157","NEWT:746360","NEWT:6239","NEWT:470150","NEWT:216257","NEWT:102169","NEWT:9986","NEWT:4054","NEWT:73239","NEWT:226186","NEWT:1268063","NEWT:8782","NEWT:1263854","NEWT:435590","NEWT:1902","NEWT:160488","NEWT:28104","NEWT:1908","NCBITaxon:2","NEWT:985076","NEWT:1215323","NEWT:52641","NEWT:7038","NEWT:6192","NEWT:28532","NCBITaxon:38727","NEWT:353152","NEWT:2829","NEWT:366581","NEWT:216599","NEWT:216595","NEWT:51329","NEWT:243230","NEWT:8355","NEWT:9685","NEWT:7029","NEWT:1080772","NEWT:1283300","NEWT:6183","NEWT:6063","NEWT:334747","NEWT:61235","NEWT:6289","NEWT:436486","NEWT:6287","NEWT:300641","NEWT:727","NEWT:9796","NEWT:725","NEWT:170187","NEWT:260707","NCBITaxon:6191","NEWT:1836","NEWT:185431","NEWT:29760","NEWT:260704","NEWT:703612","NEWT:260705","NEWT:80863","NEWT:2697049","NEWT:105231","NEWT:1216981","NCBITaxon:6073","NEWT:884204","NEWT:6279","NEWT:1123869","NEWT:9544","NEWT:7370","NEWT:83906","NEWT:607699","NEWT:6282","NEWT:208964","NEWT:1134506","NEWT:575584","NEWT:38783","NEWT:8727","NEWT:4006","NEWT:8726","NEWT:6426","NEWT:6669","NEWT:10090","NEWT:4120","NEWT:51515","NEWT:5693","NEWT:8724","NEWT:51511","NEWT:92867","NEWT:8723","NEWT:5334","NEWT:37334","NEWT:382352","NCBITaxon:10359","NEWT:242619","NEWT:632957","NEWT:34073","NEWT:373995","NEWT:5689","NEWT:544404","NEWT:9925","NEWT:8839","NEWT:4232","NEWT:2758385","NEWT:4113","NEWT:837","NEWT:11298","NEWT:171101","NEWT:714","NEWT:36015","NEWT:421932","NEWT:196627","NEWT:5691","NEWT:48479","NEWT:627025","NEWT:1097677","NEWT:61674","NEWT:1117957","NEWT:9913","NEWT:4100","NEWT:1076","NEWT:6763","NEWT:803","NEWT:29722","NEWT:380394","NEWT:1692259","NEWT:180066","NEWT:135588","NEWT:1843183","NEWT:58002","NEWT:326423","NEWT:4577","NEWT:1416333","NEWT:5664","NEWT:2157","NEWT:1678078","NEWT:749906","NEWT:418985","NEWT:146479","NEWT:1911079","NEWT:69373","NEWT:264203","NEWT:1480154","NEWT:1274414","NEWT:27606","NEWT:59202","NEWT:9975","NEWT:9612","NEWT:38865","NEWT:51953","NEWT:3197","NEWT:9615","NEWT:10299","NEWT:860688","NEWT:36329","NEWT:1147787","NCBITaxon:3044782","NEWT:72407","NEWT:349741","NEWT:9605","NEWT:9606","NEWT:157295","NEWT:641501","NEWT:7668","NEWT:915099","NEWT:74940","NEWT:9721","NEWT:137221","NEWT:1450511","NEWT:1143193","NEWT:411901","NEWT:9838","NEWT:105884","NCBITaxon:9615","NEWT:9839","NEWT:58334","NEWT:1193501","NEWT:3055","NEWT:58331","NEWT:6326","NEWT:6689","NEWT:5476","NEWT:299767","NEWT:1274432","NEWT:1274426","NEWT:70448","NEWT:9825","NEWT:1274423","NEWT:393765","NEWT:698936","NEWT:39946","NEWT:9823","NEWT:9940","NEWT:521001","NEWT:39947","NEWT:1274420","NEWT:578458"],"pubmed":["42317313"],"ORCID":["0000-0002-9697-9107"]}}