Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Nucleic Acids Res. 2022 Jul 5;50(W1):W583-W592. doi: 10.1093/nar/gkac379.
Integrative prioritisation promotes translational use of disease genetic findings in target discovery. I report 'PiER' (http://www.genetictargets.com/PiER), web-based facilities that support ab initio and real-time genetic target prioritisation through integrative use of human disease genetics, functional genomics and protein interactions. By design, the PiER features two facilities: elementary and combinatory. The elementary facility is designed to perform specific tasks, including three online tools: eV2CG, utilising functional genomics to link disease-associated variants (particularly located at the non-coding genome) to core genes likely responsible for genetic associations in disease; eCG2PG, using knowledge of protein interactions to 'network' core genes and additional peripheral genes, producing a ranked list of core and peripheral genes; and eCrosstalk, exploiting the information of pathway-derived interactions to identify highly-ranked genes mediating crosstalk between molecular pathways. Each of elementary tasks giving results is sequentially piped to the next one. By chaining together elementary tasks, the combinatory facility automates genetics-led and network-based integrative prioritisation for genetic targets at the gene level (cTGene) and at the crosstalk level (cTCrosstalk). Together with a tutorial-like booklet describing instructions on how to use, the PiER facilities meet multi-tasking needs to accelerate computational translational medicine that leverages human disease genetics and genomics for early-stage target discovery and drug repurposing.
综合优先级排序可促进疾病遗传学发现转化为目标发现。我报告了“PiER”（http://www.genetictargets.com/PiER），这是一种基于网络的工具，通过综合利用人类疾病遗传学、功能基因组学和蛋白质相互作用，支持从头开始和实时的基因目标优先级排序。根据设计，PiER 具有两个功能：基本功能和组合功能。基本功能旨在执行特定任务，包括三个在线工具：eV2CG，利用功能基因组学将疾病相关变体（特别是位于非编码基因组中的变体）与可能导致疾病遗传关联的核心基因联系起来；eCG2PG，利用蛋白质相互作用的知识将核心基因和其他外围基因“网络”化，生成核心和外围基因的排序列表；以及 eCrosstalk，利用途径衍生相互作用的信息来识别介导分子途径之间串扰的高排名基因。每个基本任务的结果都会顺序传递到下一个任务。通过将基本任务串联起来，组合功能可以自动进行基于遗传学和网络的综合优先级排序，以确定基因水平（cTGene）和串扰水平（cTCrosstalk）的遗传靶标。该工具还附有一本类似教程的小册子，介绍了如何使用的说明，这些 PiER 功能满足了多任务处理的需求，可加速利用人类疾病遗传学和基因组学进行早期目标发现和药物再利用的计算转化医学。
