转录组学因果网络确定了精神分裂症病例与对照组人脑中差异基因调控的模式
Transcriptomic Causal Networks identified patterns of differential gene regulation in human brain from Schizophrenia cases versus controls
摘要：
共同和复杂的性状是多个基因同时相互作用和调控的结果，它们以协调的方式工作。然而，绝大多数研究集中在一个单独的基因的差异表达的时间。在这里，我们的目标是提供洞察的潜在关系的基因在人类大脑中表达的精神分裂症（SCZ）和控制的情况下。我们介绍了一种新的方法，以确定差异基因调控模式，并确定了一组必要的基因在脑组织中。我们的方法整合了遗传、转录组和Hi-C数据，并生成了一个转录组-因果网络。采用这种方法分析来自CommonMind Consortium的RNA-seq数据，我们确定了SCZ病例和对照组的差异调控模式，以揭示控制人类大脑中基因转录的机制。我们的分析确定了具有大量SCZ相关基因的模块，并评估了病例和对照组中枢纽与其下游基因的关系。此外，本研究还鉴定了脑功能必需基因，并发现了与SCZ相关的新基因。
英文摘要：
Common and complex traits are the consequence of the interaction and regulation of multiple genes simultaneously, which work in a coordinated way. However, the vast majority of studies focus on the differential expression of one individual gene at a time. Here, we aim to provide insight into the underlying relationships of the genes expressed in the human brain in cases with schizophrenia (SCZ) and controls. We introduced a novel approach to identify differential gene regulatory patterns and identify a set of essential genes in the brain tissue. Our method integrates genetic, transcriptomic, and Hi-C data and generates a transcriptomic-causal network. Employing this approach for analysis of RNA-seq data from CommonMind Consortium, we identified differential regulatory patterns for SCZ cases and control groups to unveil the mechanisms that control the transcription of the genes in the human brain. Our analysis identified modules with a high number of SCZ-associated genes as well as assessing the relationship of the hubs with their down-stream genes in both, cases and controls. In addition, the results identified essential genes for brain function and suggested new genes putatively related to SCZ.
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