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探索我的通路(PmP):一个探索人类反应组化学覆盖范围的门户。

Probe my Pathway (PmP): a portal to explore the chemical coverage of the human Reactome.

作者信息

Kwak Haejin Angela, Liu Lihua, Schapira Matthieu

机构信息

Structural Genomics Consortium, University of Toronto, 101 College Street, MaRS South Tower, Suite 700, Toronto, Ontario M5G 1L7, Canada.

Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.

出版信息

Database (Oxford). 2024 Dec 5;2024. doi: 10.1093/database/baae116.

Abstract

Deciphering pathway-phenotype associations is critical for a system-wide understanding of cells and the chemistry of life. An approach to reach this goal is to systematically modulate pathways pharmacologically. The targeted and controlled regulation of an increasing number of proteins is becoming possible, thanks to the growing list of chemical probes and chemogenomic compounds available to cell biologists, but no resource is available that directly maps these chemical tools on cellular pathways. To fill this gap, we developed Probe my Pathway (PmP), a database where high-quality chemical probes and well-characterized sets of chemogenomic compounds are mapped on all the human pathways of the Reactome database. The web interface allows users to browse the data via icicle charts or search the data for compounds, proteins, or pathways. Chemists can rapidly find pathways with low chemical coverage or explore the structural chemistry of ligands targeting specific cellular machineries. Cell biologists can look for chemical probes targeting different proteins in the same pathway or find which pathways are targeted by chemical probes of interest. PmP is updated annually and will grow with the expanding chemical tool kit produced by Target 2035 and other efforts. Database URL: https://apps.thesgc.org/pmp/.

摘要

解读信号通路与表型之间的关联对于从系统层面理解细胞和生命化学至关重要。实现这一目标的一种方法是通过药理学手段系统地调节信号通路。由于细胞生物学家可获得的化学探针和化学基因组化合物的种类不断增加,对越来越多蛋白质进行靶向和可控调节已成为可能,但尚无资源可将这些化学工具直接映射到细胞信号通路上。为填补这一空白,我们开发了“探索我的信号通路”(PmP)数据库,其中高质量的化学探针和特征明确的化学基因组化合物集被映射到Reactome数据库的所有人类信号通路上。该网络界面允许用户通过冰柱图浏览数据,或搜索化合物、蛋白质或信号通路的数据。化学家可以快速找到化学覆盖度低的信号通路,或探索靶向特定细胞机制的配体的结构化学。细胞生物学家可以寻找靶向同一信号通路中不同蛋白质的化学探针,或找出感兴趣的化学探针靶向哪些信号通路。PmP每年更新,并将随着“2035目标”及其他工作所产生的不断扩展的化学工具包而发展。数据库网址:https://apps.thesgc.org/pmp/

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