RWEN: Response-weighted elastic net for prediction of chemosensitivity of cancer cell lines

Amrita Basu, Ritwik Mitra, Han Liu, Stuart L. Schreiber, Paul A. Clemons*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Motivation: In recent years there have been several efforts to generate sensitivity profiles of collections of genomically characterized cell lines to panels of candidate therapeutic compounds. These data provide the basis for the development of in silico models of sensitivity based on cellular, genetic, or expression biomarkers of cancer cells. However, a remaining challenge is an efficient way to identify accurate sets of biomarkers to validate. To address this challenge, we developed methodology using gene-expression profiles of human cancer cell lines to predict the responses of these cell lines to a panel of compounds. Results: We developed an iterative weighting scheme which, when applied to elastic net, a regularized regression method, significantly improves the overall accuracy of predictions, particularly in the highly sensitive response region. In addition to application of these methods to actual chemical sensitivity data, we investigated the effects of sample size, number of features, model sparsity, signal-to-noise ratio, andfeature correlation on predictive performance using a simulation framework, particularly for situations where the number of covariates is much larger than sample size. While our method aims to be useful in therapeutic discovery and understanding of the basic mechanisms of action of drugs and their targets, it is generally applicable in any domain where predictions of extreme responses are of highest importance.

Original languageEnglish (US)
Pages (from-to)3332-3339
Number of pages8
JournalBioinformatics
Volume34
Issue number19
DOIs
StatePublished - Oct 1 2018

Funding

This work was supported by the National Institutes of Health (NIH) via the National Cancer Institute (NCI) Cancer Target Discovery and Development Network [grant number U01CA217848]. S.L.S. is an Investigator at the Howard Hughes Medical Institute.

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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