Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/177078
Title: | Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
Author: | Beretta, Lorenzo Barturen, Guillermo Vigone, Barbara Bellocchi, Chiara Hunzelmann, Nicolas Langhe, Ellen De Cervera i Segura, Ricard, 1960- Gerosa, Maria Kovács, László Ortega Castro, Rafaela Almeida, Isabel Cornec, Divi Chizzolini, Carlo Pers, Jacques-Olivier Makowska, Zuzanna Lesche, Ralf Kerick, Martin Alarcón Riquelme, Marta Martin, Javier PRECISESADS SSc substudy group PRECISESADS Flow Cytometry study group. |
Keywords: | Esclerodèrmia Expressió gènica Scleroderma (Disease) Gene expression |
Issue Date: | Sep-2020 |
Abstract: | Objectives: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (ssc). We performed a whole blood (WB) transcriptome analysis on rna collected in the context of the european PrecisesaDs project, aiming at characterising the pathways that differentiate ssc from controls and that are reproducible in geographically diverse populations. Methods: samples from 162 patients and 252 controls were collected in rna stabilisers. cases and controls were divided into a discovery (n=79+163; southern europe) and validation cohort (n=83+89; central- Western europe). rna sequencing was performed by an illumina assay. Functional annotations of reactome pathways were performed with the Functional analysis of individual Microarray expression (FaiMe) algorithm. in parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and rna transcripts/FaiMe scores in regression models. results significant in both populations were considered as replicated. results overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. among replicated pathways, we found a deregulation in type-i interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. rna transcripts or FaiMe scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in ssc-WB samples. Conclusions: We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with ssc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and ssc. |
Note: | Reproducció del document publicat a: https://doi.org/10.1136/annrheumdis-2020-217116 |
It is part of: | Annals of Rheumatic Disease, 2020, vol. 79, num. 9 |
URI: | http://hdl.handle.net/2445/177078 |
Related resource: | https://doi.org/10.1136/annrheumdis-2020-217116 |
ISSN: | 1468-2060 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
708195.pdf | 1.98 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License