Large-scale cytological profiling for functional analysis of bioactive compounds.
Large-scale cytological profiling for functional analysis of bioactive compounds.
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用于生物活性化合物功能分析的大规模细胞学分析。
DOI：
10.1039/c3mb70245f
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发表时间：
2013
影响因子：
--
通讯作者：
Lokey,RScott
中科院分区：
文献类型：
--
作者：
Woehrmann,MarcosH;Bray,WalterM;Durbin,JamesK;Nisam,SeanC;Michael,AliciaK;Glassey,Emerson;Stuart,JoshuaM;Lokey,RScott
Cytological profiling (CP) is an unbiased image-based screening technique that uses automated microscopy and image analysis to profile compounds based on numerous quantifiable phenotypic features. We used CP to evaluate a library of nearly 500 compounds with documented mechanisms of action (MOAs) spanning a wide range of biological pathways. We developed informatics techniques for generating dosage-independent phenotypic “fingerprints” for each compound, and for quantifying the likelihood that a compound's CP fingerprint corresponds to its annotated MOA. We identified groups of features that distinguish classes with closely related phenotypes, such as microtubule poisons vs. HSP90 inhibitors, and DNA synthesis vs. proteasome inhibitors. We tested several cases in which cytological profiles indicated novel mechanisms, including a tyrphostin kinase inhibitor involved in mitochondrial uncoupling, novel microtubule poisons, and a nominal PPAR-gamma ligand that acts as a proteasome inhibitor, using independent biochemical assays to confirm the MOAs predicted by the CP signatures. We also applied maximal-information statistics to identify correlations between cytological features and kinase inhibitory activities by combining the CP fingerprints of 24 kinase inhibitors with published data on their specificities against a diverse panel of kinases. The resulting analysis suggests a strategy for probing the biological functions of specific kinases by compiling cytological data from inhibitors of varying specificities.
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影响因子：
12.3
作者：
Lorang J;King RW
通讯作者：
King RW
SK 对微管聚合的抑制
DOI：
10.1254/jjp.82.269
发表时间：
2000
期刊：
Japanese journal of pharmacology
影响因子：
--
作者：
M. Mitsui‐Saito;N. Nakahata;Y. Ohizumi
通讯作者：
Y. Ohizumi
开发高内涵筛选检测试剂盒以加速肿瘤学研究的行动研究机制
影响因子：
--
作者：
D. Towne;Emily Nicholl;K. Comess;S. Galasinski;P. Hajduk;Vivek Abraham
通讯作者：
Vivek Abraham
影响因子：
--
作者：
Schulze CJ;Bray WM;Woerhmann MH;Stuart J;Lokey RS;Linington RG
通讯作者：
Linington RG
DOI：
10.2174/1875397300903010013
发表时间：
2009-03-24
期刊：
Current chemical genomics
影响因子：
--
作者：
Low J;Chakravartty A;Blosser W;Dowless M;Chalfant C;Bragger P;Stancato L
通讯作者：
Stancato L