Network analysis of genetic variations in Autism Spectrum Disorders

Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders with a marked genetic heterogeneity [1]. Despite it is well established that ASDs have a strong genetic component, the underlying genetic cause is unknown in the majority of cases [2]. The use of genotyping and genome-sequencing technologies lead to the identification of hundreds of candidate genes, harbouring single nucleotide variations (SNVs) and copy number variations (CNVs). More recently, the integration of genetic data with molecular pathways and molecular interactions helped to propose hypotheses concerning the molecular circuits that have a key role in the pathogenesis [1-3]. The prediction of the effects of the perturbation of some elements in a complex system like the molecular interaction network is hard. However, several works have shown that genes in network proximity regulate similar biological functions and constitute disease modules, gene neighbourhoods associated with diseases [4]. In this study, we characterize the disease modules emerging from a network analysis of ASD associated genes. We collected gene evidences from several studies available in the literature and used network propagation, which simulates the diffusion of information throughout an interactome [5], to highlight the regions of the human protein-protein interaction network that are more strongly influenced by the genetic variations. Our approach provides a framework that will underline the functional relation between novel candidate genes and those "hot" network regions (modules of interacting genes) densely populated by ASD associated genes. References 1. A.S. Cristino, et al. Molecular Psychiatry (2014), 19, 294-301. 2. D. Pinto, et al. Nature (2010), 466, 368-372. 3. B.J. O'Roak, et al. Nature (2012), 485, 246-250. 4. S.D. Ghiassan, et al. PLOS Comput. Bio. (2015), 11 (4). 5. E. Mosca, et al., PLOS One (2014), 9 (12).