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基于网络的自闭症谱系障碍的基因组学、表观基因组学和转录组学综合分析。

Network-Based Integrative Analysis of Genomics, Epigenomics and Transcriptomics in Autism Spectrum Disorders.

机构信息

Institute of Biomedical Technologies, Italian National Research Council, Via Fratelli Cervi 93, 20090 Segrate (MI), Italy.

Department of Industrial and Information Engineering, University of Pavia, Via Ferrata 5, 27100 Pavia, Italy.

出版信息

Int J Mol Sci. 2019 Jul 9;20(13):3363. doi: 10.3390/ijms20133363.

Abstract

Current studies suggest that autism spectrum disorders (ASDs) may be caused by many genetic factors. In fact, collectively considering multiple studies aimed at characterizing the basic pathophysiology of ASDs, a large number of genes has been proposed. Addressing the problem of molecular data interpretation using gene networks helps to explain genetic heterogeneity in terms of shared pathways. Besides, the integrative analysis of multiple omics has emerged as an approach to provide a more comprehensive view of a disease. In this work, we carry out a network-based meta-analysis of the genes reported as associated with ASDs by studies that involved genomics, epigenomics, and transcriptomics. Collectively, our analysis provides a prioritization of the large number of genes proposed to be associated with ASDs, based on genes' relevance within the intracellular circuits, the strength of the supporting evidence of association with ASDs, and the number of different molecular alterations affecting genes. We discuss the presence of the prioritized genes in the SFARI (Simons Foundation Autism Research Initiative) database and in gene networks associated with ASDs by other investigations. Lastly, we provide the full results of our analyses to encourage further studies on common targets amenable to therapy.

摘要

目前的研究表明,自闭症谱系障碍(ASD)可能是由许多遗传因素引起的。事实上,综合考虑旨在描述 ASD 基本病理生理学的多项研究,已经提出了大量基因。使用基因网络解决分子数据解释问题有助于根据共享途径解释遗传异质性。此外,对多种组学的综合分析已成为提供疾病更全面视图的一种方法。在这项工作中,我们对涉及基因组学、表观基因组学和转录组学的研究报告的与 ASDs 相关的基因进行了基于网络的荟萃分析。总的来说,我们的分析根据基因在细胞内回路中的相关性、与 ASDs 相关的关联证据的强度以及影响基因的不同分子改变的数量,对与 ASDs 相关的大量基因进行了优先级排序。我们讨论了在 SFARI(西蒙斯基金会自闭症研究倡议)数据库中存在的优先基因,并讨论了其他研究中与 ASDs 相关的基因网络。最后,我们提供了我们分析的全部结果,以鼓励对可治疗的共同靶点进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd2/6651137/ba13da067f2d/ijms-20-03363-g001.jpg

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