小柯机器人

英国欧洲生物信息研究所（EMBL-EBI）Pedro Beltrao团队近期取得重要工作进展，他们研究利用遗传关联的网络扩展定义了人类细胞生物学的多效性图谱。相关研究成果2023年2月23日在线发表于《自然—遗传学》杂志上。

据介绍，相互作用的蛋白质往往具有相似的功能，影响着相同的生物特性。相互作用网络可用于扩展全基因组关联研究中候选性状相关基因的列表。

研究人员对1002个人类特征进行了基于网络的特征相关基因扩增，表明这恢复了已知的疾病基因或药物靶点。网络扩展分数的相似性确定了可能共享潜在遗传和生物学过程的特征组。研究人员鉴定了73个与多种性状相关的多效性基因模块，这些模块富含参与蛋白质泛素化和RNA加工等过程的基因。与基因缺失研究相反，这里定义的多效性捕捉了多细胞相关过程。研究人员展示了与人类疾病相关模块的例子，这些模块富含具有已知致病性变异的基因，可用于绘制已批准药物的靶点，以便于重新利用。

最后，研究人员阐述了如何使用网络扩展评分来研究炎症性肠病全基因组关联研究位点的基因，并将炎症性肠疾病相关基因与强大的功能和遗传支持联系起来。

附：英文原文

Title: Network expansion of genetic associations defines a pleiotropy map of human cell biology

Author: Barrio-Hernandez, Inigo, Schwartzentruber, Jeremy, Shrivastava, Anjali, del-Toro, Noemi, Gonzalez, Asier, Zhang, Qian, Mountjoy, Edward, Suveges, Daniel, Ochoa, David, Ghoussaini, Maya, Bradley, Glyn, Hermjakob, Henning, Orchard, Sandra, Dunham, Ian, Anderson, Carl A., Porras, Pablo, Beltrao, Pedro

Issue&Volume: 2023-02-23

Abstract: Interacting proteins tend to have similar functions, influencing the same organismal traits. Interaction networks can be used to expand the list of candidate trait-associated genes from genome-wide association studies. Here, we performed network-based expansion of trait-associated genes for 1,002 human traits showing that this recovers known disease genes or drug targets. The similarity of network expansion scores identifies groups of traits likely to share an underlying genetic and biological process. We identified 73 pleiotropic gene modules linked to multiple traits, enriched in genes involved in processes such as protein ubiquitination and RNA processing. In contrast to gene deletion studies, pleiotropy as defined here captures specifically multicellular-related processes. We show examples of modules linked to human diseases enriched in genes with known pathogenic variants that can be used to map targets of approved drugs for repurposing. Finally, we illustrate the use of network expansion scores to study genes at inflammatory bowel disease genome-wide association study loci, and implicate inflammatory bowel disease-relevant genes with strong functional and genetic support.

DOI: 10.1038/s41588-023-01327-9

Source: https://www.nature.com/articles/s41588-023-01327-9

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex