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Trac QT, Pawitan Y, Mou T, Erkers T, Östling P, Bohlin A, Österroos A, Vesterlund M, Jafari R, Siavelis I, Bäckvall H, Kiviluoto S, Orre LM, Rantalainen M, Lehtiö J, Lehmann S, Kallioniemi O, Vu TN
NPJ Precis Oncol 7 (1) 32 [2023-03-24; online 2023-03-24]
Despite some encouraging successes, predicting the therapy response of acute myeloid leukemia (AML) patients remains highly challenging due to tumor heterogeneity. Here we aim to develop and validate MDREAM, a robust ensemble-based prediction model for drug response in AML based on an integration of omics data, including mutations and gene expression, and large-scale drug testing. Briefly, MDREAM is first trained in the BeatAML cohort (n = 278), and then validated in the BeatAML (n = 183) and two external cohorts, including a Swedish AML cohort (n = 45) and a relapsed/refractory acute leukemia cohort (n = 12). The final prediction is based on 122 ensemble models, each corresponding to a drug. A confidence score metric is used to convey the uncertainty of predictions; among predictions with a confidence score >0.75, the validated proportion of good responders is 77%. The Spearman correlations between the predicted and the observed drug response are 0.68 (95% CI: [0.64, 0.68]) in the BeatAML validation set, -0.49 (95% CI: [-0.53, -0.44]) in the Swedish cohort and 0.59 (95% CI: [0.51, 0.67]) in the relapsed/refractory cohort. A web-based implementation of MDREAM is publicly available at https://www.meb.ki.se/shiny/truvu/MDREAM/ .
Bioinformatics Support for Computational Resources [Service]
PubMed 36964195
DOI 10.1038/s41698-023-00374-z
Crossref 10.1038/s41698-023-00374-z
pmc: PMC10039068
pii: 10.1038/s41698-023-00374-z