20.500.12556/DKUM-91257 Identification of novel loci involved in adalimumab response in Crohn’s disease patients using integration of genome profiling and isoform-level immune-cell deconvoluted transcriptome profiling of colon tissue Crohn’s disease is a consequence of dysregulated inflammatory response to the host’s microbiota. Although anti-TNF treatment improves the quality of the patient’s life, a large proportion of patients lose response to the treatment. The past decade of research has led to a continuum of studies showcasing the heterogeneity of anti-TNF response; thus, the aim of the present study was to dissect transcriptome-wide findings to transcript isoform specific levels and combine the analyses with refined information of immune cell landscapes in colon tissue, and subsequently select promising candidates using gene ontology and genomic integration. We enrolled Slovenian Crohn’s disease patients who were naïve with respect to adalimumab treatment. We performed colon tissue RNA sequencing and peripheral blood mononuclear cell DNA genotyping with a subsequent contemporary integrative approach to combine immune cell deconvoluted isoform transcript specific transcriptome analysis, gene ontology layering and genomic data. We identified nine genes (MACF1, CTSE, HDLBP, HSPA9, HLA-DMB, TAP2, LGMN, ANAPC11, ACP5) with 15 transcripts and 16 variants involved in the adalimumab response. Our study identified loci, some of which were previously shown to contribute to inflammatory bowel disease susceptibility, as novel loci involved in adalimumab response in Crohn’s disease patients. Crohn’s disease adalimumab transcriptome isoforms deconvolution Crohnova bolezen adalimumab transkriptom izoforme dekonvolucija true false true MDPI Angleški jezik Slovenski jezik https://www.mdpi.com/journal/pharmaceutics © 2022 by the authors Znanstveno delo 2024-12-05 08:58:10 2024-12-05 09:18:36 2025-05-09 13:44:35 0000-00-00 00:00:00 2022 0 0 Str. 1-16 št. 9, št. članka 1893 Letn. 14 Sep. 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2022-08-10 2022-09-02 2022-09-07 616.3 120609795 10.3390/pharmaceutics14091893 1999-4923 Gorenjak_2022_Identification_of_Novel_Loci_Involved.pdf Gorenjak_2022_Identification_of_Novel_Loci_Involved.pdf 1 FB8DF46C9A5621E82619426E782CB8F4 463baa2a6b2685cbb81bf05f5807f180e7d7598bf12f1e1bc2ebae9e61339edd 4589d618-b2e1-11ef-9aff-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=187103 https://doi.org/10.3390/pharmaceutics14091893 1 ad0493f6-b2de-11ef-9aff-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=187101 Medicinska fakulteta Fakulteta za kemijo in kemijsko tehnologijo 0 0 0