基于网络的自闭症谱系障碍基因关联方法。

IF 2.8 Q2 MATHEMATICAL & COMPUTATIONAL BIOLOGY Frontiers in bioinformatics Pub Date : 2024-03-08 eCollection Date: 2024-01-01 DOI:10.3389/fbinf.2024.1295600
Neta Zadok, Gil Ast, Roded Sharan
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引用次数: 0

摘要

自闭症谱系障碍(ASD)是一种高度遗传的复杂疾病,影响着1%的人口,但其潜在的分子机制却在很大程度上不为人知。在这里,我们通过将基因组尺度数据与网络传播方法相结合,研究了预测 ASD 致病基因的问题。我们构建了一个预测器,它整合了多个 omic 数据集,这些数据集评估了基因组、转录组、蛋白质组和磷酸蛋白组与 ASD 的关联。在交叉验证中,我们的预测器得出的平均 ROC 曲线下面积为 0.87,精度-召回曲线下面积为 0.89。我们进一步证明,它优于以前的自闭症关联基因水平预测方法。最后,我们还表明,我们可以使用该模型预测与精神分裂症相关的基因,而精神分裂症与自闭症具有相同的遗传成分。
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A network-based method for associating genes with autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable complex disease that affects 1% of the population, yet its underlying molecular mechanisms are largely unknown. Here we study the problem of predicting causal genes for ASD by combining genome-scale data with a network propagation approach. We construct a predictor that integrates multiple omic data sets that assess genomic, transcriptomic, proteomic, and phosphoproteomic associations with ASD. In cross validation our predictor yields mean area under the ROC curve of 0.87 and area under the precision-recall curve of 0.89. We further show that it outperforms previous gene-level predictors of autism association. Finally, we show that we can use the model to predict genes associated with Schizophrenia which is known to share genetic components with ASD.

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