{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:07:43Z","timestamp":1788847663853,"version":"build-2803163510"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Microbial short-chain fatty acids (SCFAs) regulate intestinal epithelial homeostasis and immune tolerance. Yet, the specific host effector genes that mediate these responses remain poorly defined, limiting the identification of biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A multi-layered\n                      <jats:italic>in silico<\/jats:italic>\n                      analysis was performed on publicly available transcriptomic data (GEO: GSE200309) derived from human intestinal epithelial cells exposed to a physiologic acetate\u2013propionate\u2013butyrate mixture (n = 6 treated; n = 6 controls). Differential expression was assessed using a two-sample Student\u2019s t-test with Benjamini\u2013Hochberg FDR correction. A dual-threshold strategy distinguished statistically robust genes (FDR &amp;lt;0.05) from exploratory, hypothesis-generating candidates (nominal p &amp;lt; 0.05). Functional enrichment (Enrichr; GO-BP, KEGG, Reactome), transcription-factor inference (ChEA3\/TRRUST), PPI network analysis (STRING v12\/Cytoscape), gene\u2013disease mapping (DisGeNET\/Open Targets), and in-sample ROC modeling were subsequently applied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Under FDR correction, TSPAN32 emerged as the sole transcriptome-wide significant gene following SCFA exposure (log\n                      <jats:sub>2<\/jats:sub>\n                      FC = +1.03; FDR = 0.043; Cohen\u2019s d \u2248 4.4), corresponding to an approximately 2.04-fold increase in expression. At the exploratory threshold, 69 additional DEGs were identified (31 upregulated, 38 downregulated; nominal p &amp;lt; 0.05), implicating histone acetylation, chromatin remodeling, microRNA biogenesis, and suppression of pro-inflammatory and apoptotic signaling. Network analysis positioned TSPAN32 as the highest-ranked hub within an immunometabolic subnetwork connecting metabolic regulators (PPARG, PPARGC1A, PLIN2), inflammatory mediators (NFKB1, RELB, IL6ST, IL10RA), epigenetic regulators (SIRT1, HDAC9), and redox-response genes (HMOX1, TXNIP). In-sample ROC analysis showed strong discrimination between SCFA-treated and control samples (AUC = 0.91; 95% CI: 0.85\u20130.98; sensitivity = 0.92; specificity = 0.88; accuracy = 0.90). To extend mechanistic inference, computational TSPAN32 knockdown was simulated by removing TSPAN32 from the STRING-derived network. This perturbation reduced network edges by 45.5%, average degree by 41.8%, largest connected component size by 56.3%, and global efficiency by 66.6%, while increasing the number of disconnected components from 1 to 5. These findings support TSPAN32 as a predicted network-stabilizing node rather than merely a differentially expressed transcript.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These hypothesis-generating findings nominate TSPAN32 as the primary SCFA-responsive effector gene in intestinal epithelial cells, coordinating epigenetic remodeling and immunometabolic reprogramming. Causal validation through functional perturbation and independent cohort replication is required before clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1847552","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:35:03Z","timestamp":1788845703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["In silico transcriptomic analysis nominates TSPAN32 as a central node of SCFA-driven immunometabolic reprogramming in intestinal epithelial cells"],"prefix":"10.3389","volume":"6","author":[{"given":"Zahra","family":"Masood","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, National University of Medical Sciences (NUMS)","place":["Rawalpindi, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqra","family":"Sarwar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, National University of Medical Sciences (NUMS)","place":["Rawalpindi, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Sanam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, National University of Medical Sciences (NUMS)","place":["Rawalpindi, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, National University of Sciences and Technology (NUST)","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Zulfiqah","family":"Sadikan","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak","place":["Ipoh, Perak, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1080\/14728222.2024.2389203","article-title":"The emerging role of Tetraspanin 32 in autoimmune diseases: from discovery to relevant theranostics?","volume":"28","author":"Fagone","year":"2024","journal-title":"Expert Opin. 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