Molecular network analysis enhances understanding of the biology of mental disorders

Abstract

Summary We provide an introduction to network theory, evidence to support a connection between molecular network structure and neuropsychiatric disease, and examples of how network approaches can expand our knowledge of the molecular bases of these diseases. Without systematic methods to derive their biological meanings and inter-relatedness, the many molecular changes associated with neuropsychiatric disease, including genetic variants, gene expression changes and protein differences, present an impenetrably complex set of findings. Network approaches can potentially help integrate and reconcile these findings, as well as provide new insights into the molecular architecture of neuropsychiatric diseases. Network approaches to neuropsychiatric disease are still in their infancy, and we discuss what might be done to improve their prospects.

Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring

“…The co-expression profiles shown in Figures 2 and 3 are particularly intriguing as co-regulation networks in recent years have been closely related to tissue-and cell type-specific biological functions and disturbances (Kopp et al, 2015; Monaco et al, 2015; Richiardi et al, 2015; Rotival and Petretto, 2014). Co-expression patterns in the brain are particularly of interest given the developmental concept of complex neuropsychiatric disorders, where it has been historically difficult to identify single causal molecular relationships (Gaiteri et al, 2014; Grennan et al, 2014). While the exact nature of the correlations between different genes and how germline THC exposure affects these relationships in subsequent progeny remains to be explored, our observations emphasize the importance of studying functional networks of genes in relation to cannabis exposure in the future.…”

Functional and Genomic Features of Human Genes Mutated in Neuropsychiatric Disorders

“…Of special interest, from a systems biology perspective, we found several topographic parameters of protein-protein interaction networks that were significant for NPD genes [30, 31]. We found that 66 NPD genes are known to be druggable, a finding of relevance for development of novel therapeutic interventions [19].…”

Current Practice of Genetics Research of Psychiatric Disorders

“…The field has moved past looking for simple Mendelian factors, and towards identifying functional aspects of the molecular changes underlying challenging complex disorders. Today, pathway analysis, network analysis [15,16] and in silico prediction of functional variation produced by coding variants are common practice. Functional analysis of non-coding variants is a major challenge facing the field [17].…”