Psychoactive pharmaceuticals as environmental contaminants may disrupt highly inter-connected nodes in an Autism-associated protein-protein interaction network

BMC Bioinformatics

Research

Michael A Thomas¹  Ken A Aho¹  Gaurav Kaushik¹ 

[1] Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, 83209-8007, Pocatello, ID, USA;

关键词: Autism Spectrum Disorder;    Autism Spectrum Disorder;    Valproate;    Venlafaxine;    Betweenness Centrality;   

DOI  :  10.1186/1471-2105-16-S7-S3

来源: Springer

【 摘 要 】

BackgroundMost cases of idiopathic autism spectrum disorder (ASD) likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a fetus to minute concentrations of pharmaceuticals, such as carbamazepine (CBZ), venlafaxine (VNX) and fluoxetine (FLX). Unmetabolized pharmaceuticals reach drinking water through a variety of routes, including ineffectively treated sewage. Previous studies in our laboratory examined the extent to which gene sets were enriched in minnow brains treated with pharmaceuticals. Here, we tested the hypothesis that genes in fish brains and human cell cultures, significantly enriched by pharmaceuticals, would have distinct characteristics in an ASD-associated protein interaction network. We accomplished this by comparing these groups using 10 network indices.ResultsA network of 7212 proteins and 33,461 interactions was generated. We found that network characteristics for enriched gene sets for particular pharmaceuticals were distinct from each other, and were different from non-enriched ASD gene sets. In particular, genes in fish brains, enriched by CBZ and VNX 1) had higher network importance than that in the overall network, and those enriched by FLX, and 2) were distinct from FLX and non-enriched ASD genes in multivariate network space. Similarly, genes in human cell cultures enriched by pharmaceutical mixtures (at environmental concentrations) and valproate (at clinical dosages) had similar network signatures, and had greater network importance than genes in the overall ASD network.ConclusionsThe results indicate that important gene sets in the ASD network are particularly susceptible to perturbation by pharmaceuticals at environmental concentrations.

【 授权许可】

Unknown   
© Kaushik et al.; licensee BioMed Central Ltd. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.