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

Author(s)

Feltrin, Arthur Sant'Anna ^[1] ; Tahira, Ana Carolina ^[2] ; Simoes, Sergio Nery ^[3] ; Brentani, Helena ^{[2, 4, 5]} ; Martins, Jr., David Correa ^[1]

Affiliation

^[1] Fed Univ ABC UFABC, Ctr Math Computat & Cognit, Santo Andre, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, LIM23, Inst Psiquiatria, Sao Paulo, SP - Brazil

^[3] Fed Inst Educ Sci & Technol Espirito Santo, Serra, ES - Brazil

^[4] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Inst Psiquiatria, Sao Paulo, SP - Brazil

^[5] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 14, n. 1 JAN 15 2019.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 11/04956-6 - Copy Number Variation in Verbal and Non-verbal patients with Autism Spectrum Disorders
• Grantee: Viviane Neri de Souza Reis
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/50761-2 - Models and methods of e-Science for life and agricultural sciences
• Grantee: Roberto Marcondes Cesar Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/00041-1 - Co-expression study among Y chromosome genes and autosomal genes and its relation to Autism Spectrum Disorders (ASD)
• Grantee: Ana Carolina Tahira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/10488-3 - Comparison of methods for prioritization of genes associated to neurodevelopment disorders
• Grantee: Arthur Sant'Anna Feltrin
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/01587-0 - Storage, modeling and analysis of dynamical systems for e-Science applications
• Grantee: João Eduardo Ferreira
• Support Opportunities: Research Grants - eScience and Data Science Program - Thematic Grants