دورية أكاديمية
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients.
| العنوان: | Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. |
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| المؤلفون: | Beretta, Lorenzo, Barturen, Guillermo, Vigone, Barbara, Bellocchi, Chiara, Hunzelmann, Nicolas, De Langhe, Ellen, Cervera, Ricard, 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 Eugenia, Martin, Javier, PRECISESADS SSc substudy group, PRECISESADS Flow Cytometry study group |
| سنة النشر: | 2020 |
| المجموعة: | Sistema Sanitario Público de Andalucía (SSPA): Repositorio |
| مصطلحات موضوعية: | autoimmune diseases, epidemiology, systemic sclerosis, Adult, Aged, Autoimmunity, Cohort Studies, Europe, Female, Gene Expression Profiling, Genome-Wide Association Study, Humans, Immunophenotyping, Interferon Type I, Male, Microarray Analysis, Middle Aged, Scleroderma, Systemic, Sequence Analysis, RNA, Signal Transduction, Toll-Like Receptors, Transcriptome |
| الوصف: | 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. 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. 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. 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1468-2060 |
| العلاقة: | http://hdl.handle.net/10668/15780Test; PMC7456554; https://ard.bmj.com/content/annrheumdis/79/9/1218.full.pdfTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456554/pdfTest |
| DOI: | 10.1136/annrheumdis-2020-217116 |
| الإتاحة: | https://doi.org/10.1136/annrheumdis-2020-217116Test http://hdl.handle.net/10668/15780Test https://ard.bmj.com/content/annrheumdis/79/9/1218.full.pdfTest https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456554/pdfTest |
| حقوق: | Attribution-NonCommercial 4.0 International ; http://creativecommons.org/licenses/by-nc/4.0Test/ ; open access |
| رقم الانضمام: | edsbas.3627B28D |
| قاعدة البيانات: | BASE |
| تدمد: | 14682060 |
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| DOI: | 10.1136/annrheumdis-2020-217116 |