{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:04:37Z","timestamp":1789981477851,"version":"4.0.1"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy","award":["32154\/18\/16.12.2024"],"award-info":[{"award-number":["32154\/18\/16.12.2024"]}],"id":[{"id":"https:\/\/ror.org\/051h0cw83","id-type":"ROR","asserted-by":"crossref"}]},{"award":["32154\/18\/16.12.2024"],"award-info":[{"award-number":["32154\/18\/16.12.2024"]}],"id":[{"id":"https:\/\/ror.org\/051h0cw83","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Mitochondrial dysfunction and immune activation are reported across many chronic diseases, yet whether such shared signals are reproducible across independent cohorts is rarely tested. We compared the peripheral blood transcriptomes of two clinically distinct disorders, pulmonary arterial hypertension (PAH) and bipolar disorder (BD), to determine which shared transcriptomic signals remain directionally concordant across independent cohorts. Methods: Five public microarray cohorts (two PAH, three BD) were analyzed through differential expression, Hallmark gene set enrichment, and weighted gene co-expression network analysis. Instead of focusing on overlapping genes, we quantified the directional reproducibility of pathway-level signals using a stability index, evaluated against chance baselines, permutation testing, and complementary reproducibility metrics. Results: Both disorders converged on an overlapping mitochondrial\u2013immune transcriptional program, and the interferon-\u03b1 response was the only Hallmark pathway with positive normalized enrichment score (NES) values across all five cohorts and was significantly enriched in four of them. Beyond the interferon response, the broader pathway signature was directionally concordant across the two PAH cohorts (stability index = 0.66; Spearman \u03c1 = 0.61) but not across the three BD cohorts (0.22; \u03c1 = 0.14). Conclusions: PAH and BD share a peripheral mitochondrial\u2013immune transcriptional program whose most reproducible element is type I interferon signaling, a signal directionally preserved across all cohorts despite differences in blood fraction. The broader transcriptomic program showed variable reproducibility that depended in part on the blood fraction sampled, highlighting the importance of evaluating both reproducibility and sample characteristics before inferring shared disease biology.<\/jats:p>","DOI":"10.3390\/genes17091147","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type I Interferon Emerges as the Reproducible Core of a Shared Mitochondrial\u2013Immune Transcriptomic Signature in Pulmonary Arterial Hypertension and Bipolar Disorder"],"prefix":"10.3390","volume":"17","author":[{"given":"Cristina Ioana","family":"Stoica","sequence":"first","affiliation":[{"name":"Department of Therapeutical Chemistry, Faculty of Pharmacy, UMF \u201cIuliu Ha\u021bieganu\u201d Cluj Napoca, 12 Ion Creang\u0103 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8621-8662","authenticated-orcid":false,"given":"C\u0103t\u0103lin","family":"Araniciu","sequence":"additional","affiliation":[{"name":"Department of Therapeutical Chemistry, Faculty of Pharmacy, UMF \u201cIuliu Ha\u021bieganu\u201d Cluj Napoca, 12 Ion Creang\u0103 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ioana Andrada","family":"Ionu\u021b","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, UMF \u201cIuliu Ha\u021bieganu\u201d Cluj Napoca, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8453-3642","authenticated-orcid":false,"given":"Anca","family":"Stana","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, UMF \u201cIuliu Ha\u021bieganu\u201d Cluj Napoca, 41 Victor Babe\u0219 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0297-7697","authenticated-orcid":false,"given":"Smaranda Dafina","family":"Oniga","sequence":"additional","affiliation":[{"name":"Department of Therapeutical Chemistry, Faculty of Pharmacy, UMF \u201cIuliu Ha\u021bieganu\u201d Cluj Napoca, 12 Ion Creang\u0103 Street, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wu, C., Wang, Z., Luo, Y., Sun, H., Li, R., Liu, W., Xu, F., Zhang, B., and Peng, Y. 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