Assessment of complementarity of WGCNA and NERI results for identification of modules associated to schizophrenia spectrum disorders

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art_FELTRIN_Assessment_of_complementarity_of_WGCNA_and_NERI_results_2019.PDF (2.47 MB)
Citações na Scopus
20
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
FELTRIN, Arthur Sant'Anna
SIMOES, Sergio Nery
MARTINS JR., David Correa
Citação
PLOS ONE, v.14, n.1, article ID e0210431, 22p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Psychiatric disorders involve both changes in multiple genes as well different types of variations. As such, gene co-expression networks allowed the comparison of different stages and parts of the brain contributing to an integrated view of genetic variation. Two methods based on co-expression networks presents appealing results: Weighted Gene Correlation Network Analysis (WGCNA) and Network-Medicine Relative Importance (NERI). By selecting two different gene expression databases related to schizophrenia, we evaluated the biological modules selected by both WGCNA and NERI along these databases as well combining both WGCNA and NERI results (WGCNA-NERI). Also we conducted a enrichment analysis for the identification of partial biological function of each result (as well a replication analysis). To appraise the accuracy of whether both algorithms (as well our approach, WGCNA-NERI) were pointing to genes related to schizophrenia and its complex genetic architecture we conducted the MSET analysis, based on a reference gene list of schizophrenia database (SZDB) related to DNA Methylation, Exome, GWAS as well as copy number variation mutation studies. The WGCNA results were more associated with inflammatory pathways and immune system response; NERI obtained genes related with cellular regulation, embryological pathways e cellular growth factors. Only NERI were able to provide a statistical meaningful results to the MSET analysis (for Methylation and de novo mutations data). However, combining WGCNA and NERI provided a much more larger overlap in these two categories and additionally on Transcriptome database. Our study suggests that using both methods in combination is better for establishing a group of modules and pathways related to a complex disease than using each method individually. NERI is available at: https://bitbucket.org/sergionery/neri.
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URI
https://observatorio.fm.usp.br/handle/OPI/30896
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPS
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/23