StopkB：一个无意识抑制疗法的全面知识库
StopKB: a comprehensive knowledgebase for nonsense suppression therapies
影响因子:3.60000
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
摘要
废话的变化以早产密码子为特征，在人类遗传疾病以及癌症易感性中起着重要作用。尽管有较高的患病率，但针对过早终止密码子的有效治疗策略仍然是一个挑战。为了理解和探索所涉及的复杂机制，我们开发了StopKB，这是一个全面的知识基础，该知识库从多个来源汇总了有关无意义变化，相关基因，疾病和表型的数据。 StopkB识别637 317独特的胡说八道，分布在18 022个人类基因上，并与3206种疾病和7765个表型相关。值得注意的是，这些变化中约有32％被归类为无义介导的mRNA衰变不敏感的，可能代表了无义抑制疗法的合适靶标。我们还提供了一个交互式的Web界面，以促进有效，直观的数据探索，使研究人员和临床医生能够浏览无意义变化的复杂景观。 StopKB代表了推进精确医学研究的宝贵资源，更具体地说，是针对与胡说八道有关的遗传疾病的有针对性治疗干预措施的发展。数据库URL：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/.