Biologically informed deep neural network for prostate cancer discovery
Menée à partir de données de séquençage de l'exome tumoral ou constitutionnel de 1 013 patients atteints d'un cancer de la prostate, cette étude met en évidence la performance d'un modèle, basé sur la technologie des réseaux de neurones profonds, pour prédire le degré d'agressivité de la maladie
The determination of molecular features that mediate clinically aggressive phenotypes in prostate cancer remains a major biological and clinical challenge1,2. Recent advances in interpretability of machine learning models as applied to biomedical problems may enable discovery and prediction in clinical cancer genomics3–5. Here we developed P-NET—a biologically informed deep learning model—to stratify patients with prostate cancer by treatment-resistance state and evaluate molecular drivers of treatment resistance for therapeutic targeting through complete model interpretability. We demonstrate that P-NET can predict cancer state using molecular data with a performance that is superior to other modelling approaches. Moreover, the biological interpretability within P-NET revealed established and novel molecularly altered candidates, such as MDM4 and FGFR1, which were implicated in predicting advanced disease and validated in vitro. Broadly, biologically informed fully interpretable neural networks enable preclinical discovery and clinical prediction in prostate cancer and may have general applicability across cancer types.
Nature , article en libre accès, 2021