Predicting tumor cell line response to drug pairs with deep learning View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12-21

AUTHORS

Fangfang Xia, Maulik Shukla, Thomas Brettin, Cristina Garcia-Cardona, Judith Cohn, Jonathan E. Allen, Sergei Maslov, Susan L. Holbeck, James H. Doroshow, Yvonne A. Evrard, Eric A. Stahlberg, Rick L. Stevens

ABSTRACT

BACKGROUND: The National Cancer Institute drug pair screening effort against 60 well-characterized human tumor cell lines (NCI-60) presents an unprecedented resource for modeling combinational drug activity. RESULTS: We present a computational model for predicting cell line response to a subset of drug pairs in the NCI-ALMANAC database. Based on residual neural networks for encoding features as well as predicting tumor growth, our model explains 94% of the response variance. While our best result is achieved with a combination of molecular feature types (gene expression, microRNA and proteome), we show that most of the predictive power comes from drug descriptors. To further demonstrate value in detecting anticancer therapy, we rank the drug pairs for each cell line based on model predicted combination effect and recover 80% of the top pairs with enhanced activity. CONCLUSIONS: We present promising results in applying deep learning to predicting combinational drug response. Our feature analysis indicates screening data involving more cell lines are needed for the models to make better use of molecular features. More... »

PAGES

486

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12859-018-2509-3

DOI

http://dx.doi.org/10.1186/s12859-018-2509-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110822704

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30577754


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