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深度神经发育障碍共病基因风险的深度多任务学习(DeepND)

DeepND: Deep multitask learning of gene risk for comorbid neurodevelopmental disorders.

作者信息

Beyreli Ilayda, Karakahya Oguzhan, Cicek A Ercument

机构信息

Department of Computer Engineering, Bilkent University, Ankara 06810, Turkey.

Computational Biology Department, Carnegie Mellon University, Pittsburgh, 15213 PA, USA.

出版信息

Patterns (N Y). 2022 Jun 2;3(7):100524. doi: 10.1016/j.patter.2022.100524. eCollection 2022 Jul 8.

Abstract

Autism spectrum disorder and intellectual disability are comorbid neurodevelopmental disorders with complex genetic architectures. Despite large-scale sequencing studies, only a fraction of the risk genes was identified for both. We present a network-based gene risk prioritization algorithm, DeepND, that performs cross-disorder analysis to improve prediction by exploiting the comorbidity of autism spectrum disorder (ASD) and intellectual disability (ID) via multitask learning. Our model leverages information from human brain gene co-expression networks using graph convolutional networks, learning which spatiotemporal neurodevelopmental windows are important for disorder etiologies and improving the state-of-the-art prediction in single- and cross-disorder settings. DeepND identifies the prefrontal and motor-somatosensory cortex (PFC-MFC) brain region and periods from early- to mid-fetal and from early childhood to young adulthood as the highest neurodevelopmental risk windows for ASD and ID. We investigate ASD- and ID-associated copy-number variation (CNV) regions and report our findings for several susceptibility gene candidates. DeepND can be generalized to analyze any combinations of comorbid disorders.

摘要

自闭症谱系障碍和智力残疾是具有复杂遗传结构的共病神经发育障碍。尽管进行了大规模测序研究,但这两种疾病仅鉴定出一小部分风险基因。我们提出了一种基于网络的基因风险优先级算法DeepND,该算法通过多任务学习利用自闭症谱系障碍(ASD)和智力残疾(ID)的共病情况进行跨疾病分析,以提高预测能力。我们的模型利用图卷积网络从人类大脑基因共表达网络中获取信息,了解哪些时空神经发育窗口对疾病病因很重要,并在单疾病和跨疾病设置中改进了当前的预测水平。DeepND确定前额叶和运动体感皮层(PFC-MFC)脑区以及胎儿早期到中期、幼儿期到青年期为ASD和ID最高的神经发育风险窗口。我们研究了与ASD和ID相关的拷贝数变异(CNV)区域,并报告了几种候选易感基因的研究结果。DeepND可以推广到分析任何共病组合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3331/9278518/309190927dcc/fx1.jpg

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