Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2484 |
Resumo: | 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. |
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Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patientsautoimmune diseasesepidemiologysystemic sclerosisObjectives: 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.This work was supported by eU/eFPia/innovative Medicines initiative Joint Undertaking PRECISESADs Grant no. 115 565BMJRepositório Científico do Centro Hospitalar Universitário de Santo AntónioBeretta, LorenzoBarturen, GuillermoVigone, BarbaraBellocchi, ChiaraHunzelmann, NicolasDe Langhe, EllenCervera, RicardGerosa, MariaKovács, LászlóOrtega Castro, RafaelaAlmeida, IsabelCornec, DiviChizzolini, CarloPers, Jacques-OlivierMakowska, ZuzannaLesche, RalfKerick, MartinAlarcón-Riquelme, Marta EugeniaMartin, Javier2021-07-02T19:16:51Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2484engBeretta L, Barturen G, Vigone B, Bellocchi C, Hunzelmann N, De Langhe E, Cervera R, Gerosa M, Kovács L, Ortega Castro R, Almeida I, Cornec D, Chizzolini C, Pers JO, Makowska Z, Lesche R, Kerick M, Alarcón-Riquelme ME, Martin J; PRECISESADS SSc substudy group; PRECISESADS Flow Cytometry study group. Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. Ann Rheum Dis. 2020 Sep;79(9):1218-1226. doi: 10.1136/annrheumdis-2020-217116. Epub 2020 Jun 19. PMID: 32561607; PMCID: PMC7456554.1468-206010.1136/annrheumdis-2020-217116info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T11:00:51Zoai:repositorio.chporto.pt:10400.16/2484Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:41.882711Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
title |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
spellingShingle |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients Beretta, Lorenzo autoimmune diseases epidemiology systemic sclerosis |
title_short |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
title_full |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
title_fullStr |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
title_full_unstemmed |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
title_sort |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients |
author |
Beretta, Lorenzo |
author_facet |
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 |
author_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
autoimmune diseases epidemiology systemic sclerosis |
topic |
autoimmune diseases epidemiology systemic sclerosis |
description |
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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2021-07-02T19:16:51Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2484 |
url |
http://hdl.handle.net/10400.16/2484 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Beretta L, Barturen G, Vigone B, Bellocchi C, Hunzelmann N, De Langhe E, Cervera R, Gerosa M, Kovács L, Ortega Castro R, Almeida I, Cornec D, Chizzolini C, Pers JO, Makowska Z, Lesche R, Kerick M, Alarcón-Riquelme ME, Martin J; PRECISESADS SSc substudy group; PRECISESADS Flow Cytometry study group. Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. Ann Rheum Dis. 2020 Sep;79(9):1218-1226. doi: 10.1136/annrheumdis-2020-217116. Epub 2020 Jun 19. PMID: 32561607; PMCID: PMC7456554. 1468-2060 10.1136/annrheumdis-2020-217116 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
BMJ |
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BMJ |
dc.source.none.fl_str_mv |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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