{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Xlsx":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PAD000040/2025.05.08_sample_manifest.xlsx","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PAD000040/samplemanifest_bis.xlsx"],"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PAD000040/checksum.txt"],"Csv":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PAD000040/inflam_PRA_dt2.raw.csv","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PAD000040/dataset_all.npx.csv","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PAD000040/inflam_NASH_dt1.raw.csv"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["pablo.giraudi@fegato.it"],"submitter":["Pablo Giraudi"],"technology_type":["Olink affinity proteomics","Mass Spectrometry","Affinity proteomics"],"disease":["Type 2 Diabetes Mellitus","Metabolic Dysfunction-associated Steatotic Liver Disease"],"software":["Not available"],"submitter_keywords":["Human","Plasma"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PAD000040"],"tissue":["Blood Plasma"],"sample_protocol":["In the present exploratory study, we aimed to characterize circulating inflam-matory protein profiles associated with glycemic status in individuals with severe obesity. Using proximity extension assay-based (PEA) proteomics, we first identified inflammatory proteins differentially expressed across normoglycemia, prediabetes, and T2DM and examined their distributions at the individual level. We then applied unsupervised topological data analysis to determine whether multidimensional in-flammatory protein patterns define distinct patient subgroups beyond conventional glycemic classification. By combining proteomic data, clinical variables, and network analysis, this study provides a hypothesis-generating view of inflammatory hetero-geneity in obesity-related dysglycemia."],"repository":["Pride"],"modification":["Not available"],"quantification_method":[""],"data_protocol":["Proteome profiling and data processing Plasma inflammatory proteins were quantified using the Olink® Inflammation panels on the Olink Signature Q100 platform (Olink Proteomics AB), based on PEA technology. In brief, target proteins are recognized by pairs of oligonucleotide-labeled antibodies, enabling subsequent DNA amplification and quantification by microflu-idic real-time PCR. Raw cycle threshold (Ct) values underwent quality control and normalization using internal and external controls with Olink NPX Signature Software (v1.13.0). Protein abundance is reported as Normalized Protein Expression (NPX), an arbitrary unit on a log2 scale, with higher NPX values indicating higher protein levels. Data exploration and initial analyses were performed using the Olink web-based analysis platform (https://olink.com/software/olink-analyze, accessed on 2 October 2025). A total of 178 samples from 143 individuals were analyzed across two Olink plates. One sample failed quality control and was excluded. Batch effects were cor-rected using a two-step strategy in Rstudio, through standard bridge normalization (46) and the Bamboo algorithm  (47), leveraging 35 technical replicate samples (12 noDM, 12 PreDM, and 11 T2DM) processed on both plates as shared bridging controls . Consistent with previous antibody-based proteomics studies, proteins with more than 20% missing values were excluded, resulting in a final dataset of 74 inflammatory proteins (out of 92 total proteins in the Olink panel) included in downstream analyses. P-values derived from t-tests were adjusted for multiple testing using the Benjamini–Hochberg method, with adjusted p-values < 0.05 considered statistically significant."],"omics_type":["Proteomics"],"labhead":["Pablo José Giraudi"],"instrument_platform":[""],"labhead_affiliation":["Fondazione Italiana Fegato"],"submission_type":["AFFINITY"],"species":["Homo Sapiens (human)"],"publication":["42123728 Milito MM, Chiesa M, Mallia A, Papaianni GG, Regalado JT, Tiribelli C, Bonazza D, Rosso N, Palmisano S, Banfi C, Giraudi PJ. Inflammatory Proteomic Heterogeneity Beyond Glycemia Status in Severe Obesity. Int J Mol Sci. 2026 27(9):4152 10.3390/ijms27094152"],"submitter_mail":["pablodata@fegato.it"],"submitter_affiliation":["Fondazione Italiana Fegato ONLUS"],"submitter_country":["Italy"],"doi":["10.6019/PAD000040"],"pubmed_abstract":["Chronic low-grade inflammation is a key feature of obesity-associated dysglycemia, yet substantial heterogeneity exists in inflammatory responses among individuals with normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM). Whether circulating inflammatory protein profiles define distinct patient phenotypes beyond conventional glycemic classification remains incompletely understood. In this cross-sectional analysis of 142 individuals with severe obesity, plasma inflammatory proteins were quantified using Olink proximity extension assay technology. Subjects were stratified by glycemic status (noDM, normoglycemia; PreDM, prediabetes and T2DM) while maintaining comparable distributions of metabolic dysfunction-associated steatotic liver disease. Differential expression analyses were performed across glycemic groups, and unsupervised topological data analysis (TDA) was applied to identify inflammatory protein-based patient subgroups. Several inflammatory proteins were significantly upregulated in T2DM and PreDM compared with noDM, with interleukin-8 (IL-8), Fms-relatedlike tyrosine kinase 3 ligand (Flt3L), and CUB domain containing protein (CDCP1) showing the largest significant differences. NPX distributions of these proteins exhibited gradual increases across glycemic stages with substantial inter-individual variability. TDA identified seven clusters defined by distinct inflammatory protein signatures. One cluster was enriched for individuals with T2DM and characterized by coordinated upregulation of IL-8, Flt3L, CDCP1, and additional immune- and cytokine-related proteins, whereas other clusters displayed alternative inflammatory profiles that were not explained by glycemic status alone. Inflammatory proteomic profiling in severe obesity reveals both glycemia-associated protein changes and distinct inflammatory phenotypes that transcend conventional clinical classification. Integration of differential expression analysis with TDA highlights heterogeneity in inflammatory states, supporting a hypothesis-generating framework for future studies aimed at validating these proteomic patterns and clarifying their longitudinal relevance in obesity-related dysglycemia."],"pubmed_title":["Inflammatory Proteomic Heterogeneity Beyond Glycemia Status in Severe Obesity."],"pubmed_authors":["Milito Melissa M MM, Chiesa Mattia M, Mallia Alice A, Papaianni Giulia G GG, Regalado Julia T JT, Tiribelli Claudio C, Bonazza Deborah D, Rosso Natalia N, Palmisano Silvia S, Banfi Cristina C, Giraudi Pablo J PJ"],"additional_accession":[]},"is_claimable":false,"name":"Inflammatory proteomics heterogeneity beyond glycemia status in severe obesity","description":"In the present exploratory study, we aimed to characterize circulating inflam-matory protein profiles associated with glycemic status in individuals with severe obesity. Using proximity extension assay-based (PEA) proteomics, we first identified inflammatory proteins differentially expressed across normoglycemia, prediabetes, and T2DM and examined their distributions at the individual level. We then applied unsupervised topological data analysis to determine whether multidimensional in-flammatory protein patterns define distinct patient subgroups beyond conventional glycemic classification. By combining proteomic data, clinical variables, and network analysis, this study provides a hypothesis-generating view of inflammatory hetero-geneity in obesity-related dysglycemia.","dates":{"publication":"2026-06-08","submission":"2026-04-28"},"accession":"PAD000040","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:35795","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:247480","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:1599","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:12215","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NEWT:1748418","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:4615","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:3760","NEWT:1584","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:381198","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:7719","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:3349","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1916073","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:370038","NEWT:498211","NEWT:345076","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:200795","NEWT:2579791","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:260499","NEWT:410661","NEWT:329854","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:2649329","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:3715","NEWT:1538","NEWT:2065263","NEWT:177437","NEWT:717966","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:2853422","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:45972","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:2836","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:1922344","NEWT:108458","NEWT:5936","NEWT:85692","NEWT:321967","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:279010","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:415978","NEWT:1255228","NEWT:410289","NEWT:191701","NEWT:373153","NEWT:1640278","NEWT:9054","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:28128","NEWT:470","NEWT:41122","NEWT:5911","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166314","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:3726","NEWT:906914","NEWT:81231006","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:542","NEWT:2903","NEWT:185579","NEWT:872227","NEWT:13076","NEWT:2587410","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:2126337","NEWT:550","NEWT:10804","NEWT:33941","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:42410","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:771870","NEWT:51338","NEWT:9995","NEWT:575412","NEWT:28112","NEWT:49012","NEWT:28110","NEWT:6493","NEWT:10832","NEWT:6494","NEWT:6491","NEWT:50760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