{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T14:48:49Z","timestamp":1772203729084,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"Supplement_2","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Van Herk Charity"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>When phase III clinical drug trials fail their endpoint, enormous resources are wasted. Moreover, even if a clinical trial demonstrates a significant benefit, the observed effects are often small and may not outweigh the side effects of the drug. Therefore, there is a great clinical need for methods to identify genetic markers that can identify subgroups of patients which are likely to benefit from treatment as this may (i) rescue failed clinical trials and\/or (ii) identify subgroups of patients which benefit more than the population as a whole. When single genetic biomarkers cannot be found, machine learning approaches that find multivariate signatures are required. For single nucleotide polymorphism (SNP) profiles, this is extremely challenging owing to the high dimensionality of the data. Here, we introduce RAINFOREST (tReAtment benefIt prediction using raNdom FOREST), which can predict treatment benefit from patient SNP profiles obtained in a clinical trial setting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We demonstrate the performance of RAINFOREST on the CAIRO2 dataset, a phase III clinical trial which tested the addition of cetuximab treatment for metastatic colorectal cancer and concluded there was no benefit. However, we find that RAINFOREST is able to identify a subgroup comprising 27.7% of the patients that do benefit, with a hazard ratio of 0.69 (P\u2009=\u20090.04) in favor of cetuximab. The method is not specific to colorectal cancer and could aid in reanalysis of clinical trial data and provide a more personalized approach to cancer treatment, also when there is no clear link between a single variant and treatment benefit.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The R code used to produce the results in this paper can be found at github.com\/jubels\/RAINFOREST. A more configurable, user-friendly Python implementation of RAINFOREST is also provided. Due to restrictions based on privacy regulations and informed consent of participants, phenotype and genotype data of the CAIRO2 trial cannot be made freely available in a public repository. Data from this study can be obtained upon request. Requests should be directed toward Prof. Dr. H.J. Guchelaar (h.j.guchelaar@lumc.nl).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa799","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T19:14:50Z","timestamp":1599506090000},"page":"i601-i609","source":"Crossref","is-referenced-by-count":30,"title":["RAINFOREST: a random forest approach to predict treatment benefit in data from (failed) clinical drug trials"],"prefix":"10.1093","volume":"36","author":[{"given":"Joske","family":"Ubels","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine, UMC Utrecht , Utrecht, The Netherlands"},{"name":"Erasmus MC Cancer Institute, ErasmusMC , Rotterdam, The Netherlands"},{"name":"SkylineDx , Rotterdam, The Netherlands"},{"name":"Oncode Institute , Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tilman","family":"Schaefers","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, UMC Utrecht , Utrecht, The Netherlands"},{"name":"Oncode Institute , Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis","family":"Punt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht , Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk-Jan","family":"Guchelaar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center , Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen","family":"de Ridder","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, UMC Utrecht , Utrecht, The Netherlands"},{"name":"Oncode Institute , Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"2023062409322886000_btaa799-B26","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.diii.2018.05.008","article-title":"Predicting Prognosis of Resected Hepatocellular Carcinoma by Radiomics Analysis with Random Survival Forest","volume":"99","author":"Akai","year":"2018","journal-title":"Diagn. 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