Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients

Detalhes bibliográficos
Autor(a) principal: Beretta, Lorenzo
Data de Publicação: 2020
Outros Autores: 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
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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spelling 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
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv BMJ
publisher.none.fl_str_mv BMJ
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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