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A Machine Learning Platform to Optimize the Translation of Personalized Network Models to the Clinic.

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posted on 22.11.2019 by Manuela Salvucci, Arman Rahman, Alexa J. Resler, Girish M. Udupi, Deborah A. McNamara, Elaine W. Kay, Pierre Laurent-Puig, Daniel B. Longley, Patrick G. Johnston, Mark Lawler, Richard Wilson, Manuel Salto-Tellez, Sandra Van Schaeybroeck, Mairin Rafferty, William M. Gallagher, Markus Rehm, Jochen HM Prehn

PURPOSE: Dynamic network models predict clinical prognosis and inform therapeutic intervention by elucidating disease-driven aberrations at the systems level. However, the personalization of model predictions requires the profiling of multiple model inputs, which hampers clinical translation.

PATIENTS AND METHODS: We applied APOPTO-CELL, a prognostic model of apoptosis signaling, to showcase the establishment of computational platforms that require a reduced set of inputs. We designed two distinct and complementary pipelines: a probabilistic approach to exploit a consistent subpanel of inputs across the whole cohort (Ensemble) and a machine learning approach to identify a reduced protein set tailored for individual patients (Tree). Development was performed on a virtual cohort of 3,200,000 patients, with inputs estimated from clinically relevant protein profiles. Validation was carried out in an in-house stage III colorectal cancer cohort, with inputs profiled in surgical resections by reverse phase protein array (n = 120) and/or immunohistochemistry (n = 117).

RESULTS: Ensemble and Tree reproduced APOPTO-CELL predictions in the virtual patient cohort with 92% and 99% accuracy while decreasing the number of inputs to a consistent subset of three proteins (40% reduction) or a personalized subset of 2.7 proteins on average (46% reduction), respectively. Ensemble and Tree retained prognostic utility in the in-house colorectal cancer cohort. The association between the Ensemble accuracy and prognostic value (Spearman ρ = 0.43;

CONCLUSION: This study provides a generalizable framework to optimize the development of network-based prognostic assays and, ultimately, to facilitate their integration in the routine clinical workflow.

Funding

European Union Framework Programme 7 (FP7 APODECIDE, contract No. 306021). Science Foundation Ireland/Department of Enterprise and Learning Partnership Award (14/IA/2582). Science Foundation Ireland Investigator Award (13/IA/1881). Irish Cancer Society Collaborative Cancer Research Centre BREASTPREDICT (CCRC13GAL).

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The original article is available at ascopubs.org

Published Citation

Salvucci M, Rahman A, Resler AJ, Udupi GM, McNamara DA, Kay EW, Laurent-Puig P, Longley DB, Johnston PG, Lawler M, Wilson R, Salto-Tellez M, Van Schaeybroeck S, Rafferty M, Gallagher WM, Rehm M, Prehn JHM. A Machine Learning Platform to Optimize the Translation of Personalized Network Models to the Clinic. JCO Clinical Cancer Informatics. 2019;3:1-17

Publication Date

01/04/2019

Publisher

American Society of Clinical Oncology

PubMed ID

30995124

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