Omics data integration identifies ELOVL7 and MMD gene regions as novel loci for adalimumab response in patients with Crohn’s disease

Abstract

Response to anti-TNF therapy is of pivotal importance in patients with Crohn’s disease (CD). Here we integrated our and previously reported PBMC derived transcriptomic and genomic data for identification of biomarkers for discrimination between responders and non-responders to anti-TNF therapy. CD patients, who were naïve with respect to the treatment with biologicals, were enrolled in the study. DNA and RNA were extracted from peripheral blood mononuclear cells. RNA-seq was performed using BGISEQ-500. Genotyping was performed using Infinium Global Screening Array. Association regressions were carried out with 12 week response to adalimumab as an outcome variable. RNA-seq analysis confirmed 7 out of 65 previously suggested genes involved in anti-TNF response. Subsequently, analysis of single nucleotide variants in regions of confirmed genes identified 5 variants near MMD and two in ELOVL7 intronic regions associated with treatment response to anti-TNF. Functional analysis has shown that rs1465352, rs4422035 and rs78620886 are listed at H3K9ac_Pro histone modification epigenetic mark. The present study confirmed MMD and ELOVL7 involvement in anti-TNF response and revealed that the regulation of MMD and ELOVL7 gene regions in ADA response may be a part of a complex interplay extending from genetic to epigenetic and to transcriptomic level.

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn’s Disease

“…KAT2B, the epigenetic regulator, is a lysine acetyltransferase that is down-regulated in the inflamed colonic tissue of CD patients [ 36 ]. So far, few studies have reported the role of the KAT2B gene in the prediction of anti-TNF resistance in CD [ 37 , 38 ]. Mesko et al have reported that the gene panel including KAT2B may be useful for the prediction of anti-TNF responsiveness in CD [ 37 ].…”

“…Mesko et al have reported that the gene panel including KAT2B may be useful for the prediction of anti-TNF responsiveness in CD [ 37 ]. Furthermore, a recent integrative transcriptomic and genomic study by Gorenjak et al has suggested remarkable potential of KAT2B as a prognostic biomarker for anti-TNF therapy responsiveness in patients with CD [ 38 ]. However, the studies were investigational in nature and did not stress the biological interpretation of the molecular profiling data.…”

Whole-Genome DNA Methylation Sequencing Reveals Epigenetic Changes in Myelodysplastic Syndromes

“…RNA samples were analyzed by the BGISEQ-500 platform (BGI, Wuhan, China). The details of RNA-Seq could be referred to in previous reports ( 16 ).…”

MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines

“…Paired-end read (2 × 74 bp) RNA sequencing (RNAseq) was performed on a NextSeq 550 apparatus (Illumina) with a NextSeq 500/550 Mid Output Kit v2.5 (Illumina, Inc., San Diego, CA, USA). Raw FASTQ data were processed as described previously [ 44 ]. RNA expression data of MDA-MB-453, MDA-MB-231 and MFUM-BrTNBC-1 (4th passage) were compared to the MCF-7 epithelial CL.…”