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Peck, D.

Publications and source records attributed to Peck, D..

2 recordsLinked to original sources

Improving Deconvolution Methods in Biology through Open Innovation Competitions: An Application to the Connectivity Map

Do machine learning methods improve standard deconvolution techniques for gene expression data? This paper uses a unique new dataset combined with an open innovation competition to evaluate a wide range of gene-expression deconvolution approaches developed by 294 competitors from 20 countries. The objective of the competition was to separate the expression of individual genes from composite measures of gene pairs. Outcomes were evaluated using direct measurements of single genes from the same samples. Results indicate that the winning algorithm based on random forest regression outperformed the other methods in terms of accuracy and reproducibility. More traditional gaussian-mixture methods performed well and tended to be faster. The best deep learning approach yielded outcomes slightly inferior to the above methods. We anticipate researchers in the field will find the dataset and algorithms developed in this study to be a powerful research tool for benchmarking their deconvolution methods and a useful resource for multiple applications.

genomics↗

Non-oncology drugs are a source of previously unappreciated anti-cancer activity

Anti-cancer uses of non-oncology drugs have been found on occasion, but such discoveries have been serendipitous and rare. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. To accomplish this, we used PRISM, which involves drug treatment of molecularly barcoded cell lines in pools. Relative barcode abundance following treatment thus reflects cell line viability. We found that an unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines. Moreover, the killing activity of the majority of these drugs was predictable based on the molecular features of the cell lines. Follow-up of several of these compounds revealed novel mechanisms. For example, compounds that kill by inducing PDE3A-SLFN12 complex formation; vanadium-containing compounds whose killing is dependent on the sulfate transporter SLC26A2; the alcohol dependence drug disulfiram, which kills cells with low expression of metallothioneins; and the anti-inflammatory drug tepoxalin, whose killing is dependent on high expression of the multi-drug resistance gene ABCB1. These results illustrate the potential of the PRISM drug repurposing resource as a starting point for new oncology therapeutic development. The resource is available at https://depmap.org.

cancer biology↗