Document Detail


An integrated one-step system to extract, analyze and annotate all relevant information from image-based cell screening of chemical libraries.
MedLine Citation:
PMID:  20237649     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Here we report the development and validation of a complete solution to manage and analyze the data produced by image-based phenotypic screening campaigns of small-molecule libraries. In one step initial crude images are analyzed for multiple cytological features, statistical analysis is performed and molecules that produce the desired phenotypic profile are identified. A na?ve Bayes classifier, integrating chemical and phenotypic spaces, is built and utilized during the process to assess those images initially classified as "fuzzy"-an automated iterative feedback tuning. Simultaneously, all this information is directly annotated in a relational database containing the chemical data. This novel fully automated method was validated by conducting a re-analysis of results from a high-content screening campaign involving 33 992 molecules used to identify inhibitors of the PI3K/Akt signaling pathway. Ninety-two percent of confirmed hits identified by the conventional multistep analysis method were identified using this integrated one-step system as well as 40 new hits, 14.9% of the total, originally false negatives. Ninety-six percent of true negatives were properly recognized too. A web-based access to the database, with customizable data retrieval and visualization tools, facilitates the posterior analysis of annotated cytological features which allows identification of additional phenotypic profiles; thus, further analysis of original crude images is not required.
Authors:
Obdulia Rabal; Wolfgang Link; Beatriz G Serelde; James R Bischoff; Julen Oyarzabal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-21
Journal Detail:
Title:  Molecular bioSystems     Volume:  6     ISSN:  1742-2051     ISO Abbreviation:  Mol Biosyst     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-18     Completed Date:  2010-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101251620     Medline TA:  Mol Biosyst     Country:  England    
Other Details:
Languages:  eng     Pagination:  711-20     Citation Subset:  IM    
Affiliation:
Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro, 3, 28029 Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors
Cell Line
Database Management Systems
Drug Evaluation, Preclinical / statistics & numerical data*
Enzyme Inhibitors / chemistry,  pharmacology
Humans
Image Processing, Computer-Assisted / statistics & numerical data*
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Signal Transduction / drug effects
Small Molecule Libraries / chemistry*,  pharmacology*
Systems Biology
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Small Molecule Libraries; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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