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Trac, Quang Thinh; Pawitan, Yudi; Mou, Tian; Erkers, Tom; Östling, Päivi; Bohlin, Anna; Österroos, Albin; Vesterlund, Mattias; Jafari, Rozbeh; Siavelis, Ioannis; Bäckvall, Helena; Kiviluoto, Santeri; Orre, Lukas M.; Rantalainen, Mattias; Lehtiö, Janne; Lehmann, Sören; Kallioniemi, Olli; Vu, Trung Nghia

Prediction model for drug response of acute myeloid leukemia patients

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  • Medientyp: E-Artikel
  • Titel: Prediction model for drug response of acute myeloid leukemia patients
  • Beteiligte: Trac, Quang Thinh; Pawitan, Yudi; Mou, Tian; Erkers, Tom; Östling, Päivi; Bohlin, Anna; Österroos, Albin; Vesterlund, Mattias; Jafari, Rozbeh; Siavelis, Ioannis; Bäckvall, Helena; Kiviluoto, Santeri; Orre, Lukas M.; Rantalainen, Mattias; Lehtiö, Janne; Lehmann, Sören; Kallioniemi, Olli; Vu, Trung Nghia
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: npj Precision Oncology, 7 (2023) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41698-023-00374-z
  • ISSN: 2397-768X
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: AbstractDespite 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/.
  • Zugangsstatus: Freier Zugang