StopKB：全面的无义突变抑制治疗知识库
StopKB: a comprehensive knowledgebase for nonsense suppression therapies
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影响因子:3.6
分区:生物学4区 / 数学与计算生物学4区
发表日期:2024 Oct 12
作者:
Nicolas Haas, Julie Dawn Thompson, Jean-Paul Renaud, Kirsley Chennen, Olivier Poch
DOI:
10.1093/database/baae108
摘要
无义突变（由提前终止密码子引起）在人类遗传疾病和癌症易感性中起着重要作用。尽管其高发，但针对提前终止密码子的有效治疗策略仍然具有挑战性。为了理解和探索相关机制，我们开发了StopKB，这是一个整合多源数据的全面知识库，涵盖无义突变、相关基因、疾病和表型。StopKB收录了637,317个独特的无义突变，分布在18,022个人类基因中，关联3206种疾病和7765个表型。值得注意的是，大约32%的无义突变被归类为无义介导的mRNA降解（nonsense-mediated mRNA decay）不敏感，可能成为无义突变抑制治疗的潜在靶点。我们还提供了交互式网页界面，便于用户高效直观地探索数据，帮助科研人员和临床医生理解无义突变的复杂景观。StopKB为精准医学研究及针对与无义突变相关的遗传疾病的靶向治疗开发提供了宝贵资源。数据库网址：https://lbgi.fr/stopkb/。
Abstract
Nonsense variations, characterized by premature termination codons, play a major role in human genetic diseases as well as in cancer susceptibility. Despite their high prevalence, effective therapeutic strategies targeting premature termination codons remain a challenge. To understand and explore the intricate mechanisms involved, we developed StopKB, a comprehensive knowledgebase aggregating data from multiple sources on nonsense variations, associated genes, diseases, and phenotypes. StopKB identifies 637 317 unique nonsense variations, distributed across 18 022 human genes and linked to 3206 diseases and 7765 phenotypes. Notably, ∼32% of these variations are classified as nonsense-mediated mRNA decay-insensitive, potentially representing suitable targets for nonsense suppression therapies. We also provide an interactive web interface to facilitate efficient and intuitive data exploration, enabling researchers and clinicians to navigate the complex landscape of nonsense variations. StopKB represents a valuable resource for advancing research in precision medicine and more specifically, the development of targeted therapeutic interventions for genetic diseases associated with nonsense variations. Database URL: https://lbgi.fr/stopkb/.