Journal Article

Differential gene regulatory pattern in the human brain from schizophrenia using transcriptomic-causal network

Kosorok, Michael R., Mendez-Giraldez, Raul, Roussos, Panos, Yazdani, Azam, Yazdani, Akram

2020

Overview

Background Common and complex traits are the consequence of the interaction and regulation of multiple genes simultaneously, therefore characterizing the interconnectivity of genes is essential to unravel the underlying biological networks. However, the focus of many studies is on the differential expression of individual genes or on co-expression analysis. Methods Going beyond analysis of one gene at a time, we systematically integrated transcriptomics, genotypes and Hi-C data to identify interconnectivities among individual genes as a causal network. We utilized different machine learning techniques to extract information from the network and identify differential regulatory pattern between cases and controls. We used data from the Allen Brain Atlas for replication. Results Employing the integrative systems approach on the data from CommonMind Consortium showed that gene transcription is controlled by genetic variants proximal to the gene (cis-regulatory factors), and transcribed distal genes (trans-regulatory factors). We identified differential gene regulatory patterns in SCZ-cases versus controls and novel SCZ-associated genes that may play roles in the disorder since some of them are primary expressed in human brain. In addition, we observed genes known associated with SCZ are not likely (OR = 0.59) to have high impacts (degree > 3) on the network. Conclusions Causal networks could reveal underlying patterns and the role of genes individually and as a group. Establishing principles that govern relationships between genes provides a mechanistic understanding of the dysregulated gene transcription patterns in SCZ and creates more efficient experimental designs for further studies. This information cannot be obtained by studying a single gene at the time.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Algorithms / Analysis / Analysis and modelling of complex systems / Bayesian causal network / Bioinformatics / Biomedical and Life Sciences / Brain / Cis/trans-regulatory factors / Computational Biology/Bioinformatics / Computer Appl. in Life Sciences / Consortia / Data integration / Ethnicity / Gene expression / Gene regulation / Genes / Genetic diversity / Genetic research / Genetic variance / Genomes / Genotypes / Information processing / Learning algorithms / Life Sciences / Machine learning / Mendelian randomization / Mental disorders / Microarrays / Research Article / Schizophrenia / Transcription / Transcription (Genetics) / Transcriptomic