MOSAIC: a chemical-genetic interaction data repository and web resource for exploring chemical modes of action

MOSAIC: a chemical-genetic interaction data repository and web resource for exploring chemical modes of action
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MOSAIC:用于探索化学作用模式的化学-遗传相互作用数据存储库和网络资源

DOI:
10.1093/bioinformatics/btx732
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发表时间:
2018
期刊:
影响因子:
5.8
通讯作者:
Myers CL.
Myers CL.
中科院分区:
生物学3区
文献类型:
--
作者:
Nelson J;Simpkins SW;Safizadeh H;Li SC;Piotrowski JS;Hirano H;Yashiroda Y;Osada H;Yoshida M;Boone C;Myers CL.

文献摘要

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概述绘制小分子之间的相互作用和遗传扰动的化学基因组学方法为未知生物活性化合物的功能注释提供了一种很有前途的策略。我们最近开发了一个新的高通量平台,用于绘制酵母中的化学-遗传(CG)相互作用图,该平台可以规模化地筛选大型化合物集合,并应用该系统为超过13,000种化合物生成CG相互作用图谱。当与现有的全球酵母遗传相互作用网络相结合时,CG相互作用配置文件可以预测以前未确定的化合物的作用模式,并发现已知药物的意想不到的二次效应。为了便于将来对这些有价值的数据进行分析,我们开发了一个名为MOSAIC的公共数据库和网络界面。该网站提供了一个方便的界面,用于查询化合物、生物过程(基因本体论术语)和基因,以获取CG信息,包括直接CG相互作用、生物过程和基因水平的靶标预测。马赛克还提供了对筛选的分子的化学结构信息、化学基因组图谱以及搜索具有结构和功能相似性的化合物的能力。化学生物学家和对分析CG相互作用网络感兴趣的计算生物学家将对此资源感兴趣,以发现具有特定作用模式的新的小分子探测器。可用性和实施MOSAIC可在http://mosaic.cs.umn.edu.Supplementary信息上获得补充数据可在生物信息学在线上获得。
SummaryChemical-genomic approaches that map interactions between small molecules and genetic perturbations offer a promising strategy for functional annotation of uncharacterized bioactive compounds. We recently developed a new high-throughput platform for mapping chemical-genetic (CG) interactions in yeast that can be scaled to screen large compound collections, and we applied this system to generate CG interaction profiles for more than 13 000 compounds. When integrated with the existing global yeast genetic interaction network, CG interaction profiles can enable mode-of-action prediction for previously uncharacterized compounds as well as discover unexpected secondary effects for known drugs. To facilitate future analysis of these valuable data, we developed a public database and web interface named MOSAIC. The website provides a convenient interface for querying compounds, bioprocesses (Gene Ontology terms) and genes for CG information including direct CG interactions, bioprocesses and gene-level target predictions. MOSAIC also provides access to chemical structure information of screened molecules, chemical-genomic profiles and the ability to search for compounds sharing structural and functional similarity. This resource will be of interest to chemical biologists for discovering new small molecule probes with specific modes-of-action as well as computational biologists interested in analysing CG interaction networks.Availability and implementationMOSAIC is available at http://mosaic.cs.umn.edu.Supplementary informationSupplementary data are available atBioinformaticsonline.