Additional file 2 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Figure S1 Validation of SKNBE transcriptome data via qPCR. Comparison between fold changes obtained with RNA sequencing and with real time qPCR of selected genes. Direction of fold change was confirmed for 9 out of 10 assayed genes. (PDF 111 kb

Additional file 12 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Table S9 Functional enrichment analysis of DEGs predominantly expressed in brain. Functional annotation of the 117 DEGs predominantly expressed in brain was performed with DAVID. The table shows the top enriched terms (Benjamini-adjusted p-value < 0.1). (XLSX 9 kb

Additional file 13 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Table S10 Functional enrichment analysis of the SKNBE DEGs. Functional annotation of the 764 DEGs was performed with DAVID. The table shows the top enriched terms (Benjamini-adjusted p-value < 0.1). (XLSX 10 kb

Additional file 15 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Table S12 Functional enrichment analysis of the modules identified by WGCNA. Functional annotation of the modules was performed with DAVID. The table reports the top 15 ranked pathways (by Benjamini adjusted p-value) relative to the genes in the blue module (N = 191), the turquoise module (N = 282), and the brown module (N = 169). (XLSX 11 kb

Additional file 9 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Table S6 Number of expressed genes in SKNBE transcriptome data according to biotype. Overview of gene biotypes in Ensembl’s annotation file, number of expressed genes for each biotype, mean length, and length range. (XLSX 9 kb

Additional file 5 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Table S4 Functional enrichment analysis of the DEGs in lymphoblastoid cell line samples. Functional annotation of the 235 DEGs was performed with DAVID [29, 30]. The table shows the top enriched terms (Benjamini-adjusted p-value < 0.1). (XLSX 9 kb

Table_9_Effects of Anti-Integrin Treatment With Vedolizumab on Immune Pathways and Cytokines in Inflammatory Bowel Diseases.docx

Background and aims<p>Despite proven clinical efficacy of vedolizumab (VDZ) for inducing and maintaining remission in patients with Crohn’s disease (CD) and ulcerative colitis (UC), subgroups of patients have no therapeutic benefit from anti-α4β7 integrin therapy with VDZ. Within this study, we aimed to identify genetic, cellular, and immunological mechanisms that define response and failure to VDZ treatment.</p>Methods<p>Intestinal RNA sequencing was performed in UC and CD patients before and at week 14 of VDZ therapy. α4β7 expression on peripheral and mucosal immune cells was assessed by flow cytometry and immunohistochemistry. Cellular modes of VDZ-mediated action were analyzed ex vivo and in VDZ-treated inflammatory bowel disease patients.</p>Results<p>Transcriptome analysis showed an impairment of signaling cascades associated with adhesion, diapedesis, and migration of granulocytes and agranulocytes upon VDZ therapy. In non-remitters to VDZ therapy, a tissue destructive and leukocyte-mediated inflammatory activity with activation of TNF-dependent pathways was present, all of which were inhibited in remitters to VDZ. Clinical remission was associated with a significant reduction of α4β7 expression on Th2 and Th17 polarized mucosal CD4⁺ T cells at week 14 of VDZ therapy and with significantly higher numbers of α4β7-expressing mucosal cells prior to the initiation of VDZ therapy compared with non-remitters.</p>Conclusion<p>Intestinal α4β7 expression prior to VDZ therapy might represent a biomarker that predicts therapeutic response to subsequent VDZ treatment. Due to high activation of TNF signaling in VDZ non-remitters, anti-TNF treatment might represent a promising therapeutic strategy in VDZ refractory patients.</p

Additional file 7 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Table S5 Summary statistics for RNA-seq on SKNBE samples. Summary statistics for RNA sequencing of knockdown samples with three different siRNAs targeting EDC3 (siEDC-1, siEDC3-2, siEDC-3) as well as control (siNC) samples relative to three replicate experiments (T1-T3). (XLSX 9 kb

Table_5_Effects of Anti-Integrin Treatment With Vedolizumab on Immune Pathways and Cytokines in Inflammatory Bowel Diseases.xls

Background and aims<p>Despite proven clinical efficacy of vedolizumab (VDZ) for inducing and maintaining remission in patients with Crohn’s disease (CD) and ulcerative colitis (UC), subgroups of patients have no therapeutic benefit from anti-α4β7 integrin therapy with VDZ. Within this study, we aimed to identify genetic, cellular, and immunological mechanisms that define response and failure to VDZ treatment.</p>Methods<p>Intestinal RNA sequencing was performed in UC and CD patients before and at week 14 of VDZ therapy. α4β7 expression on peripheral and mucosal immune cells was assessed by flow cytometry and immunohistochemistry. Cellular modes of VDZ-mediated action were analyzed ex vivo and in VDZ-treated inflammatory bowel disease patients.</p>Results<p>Transcriptome analysis showed an impairment of signaling cascades associated with adhesion, diapedesis, and migration of granulocytes and agranulocytes upon VDZ therapy. In non-remitters to VDZ therapy, a tissue destructive and leukocyte-mediated inflammatory activity with activation of TNF-dependent pathways was present, all of which were inhibited in remitters to VDZ. Clinical remission was associated with a significant reduction of α4β7 expression on Th2 and Th17 polarized mucosal CD4⁺ T cells at week 14 of VDZ therapy and with significantly higher numbers of α4β7-expressing mucosal cells prior to the initiation of VDZ therapy compared with non-remitters.</p>Conclusion<p>Intestinal α4β7 expression prior to VDZ therapy might represent a biomarker that predicts therapeutic response to subsequent VDZ treatment. Due to high activation of TNF signaling in VDZ non-remitters, anti-TNF treatment might represent a promising therapeutic strategy in VDZ refractory patients.</p

Additional file 4 of Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Table S3 Results of differential expression analysis on patients’ lymphoblastoid cell line samples. Output of differential expression analysis performed with DESeq2 [23] for the 22,123 genes that passed independent filtering. HGNC symbols could be retrieved via biomaRt package for 17,975 genes. (XLS 3186 kb