Network modeling of patients' biomolecular profiles for clinical phenotype/outcome prediction.

Journal: Scientific reports
Published Date:

Abstract

Methods for phenotype and outcome prediction are largely based on inductive supervised models that use selected biomarkers to make predictions, without explicitly considering the functional relationships between individuals. We introduce a novel network-based approach named Patient-Net (P-Net) in which biomolecular profiles of patients are modeled in a graph-structured space that represents gene expression relationships between patients. Then a kernel-based semi-supervised transductive algorithm is applied to the graph to explore the overall topology of the graph and to predict the phenotype/clinical outcome of patients. Experimental tests involving several publicly available datasets of patients afflicted with pancreatic, breast, colon and colorectal cancer show that our proposed method is competitive with state-of-the-art supervised and semi-supervised predictive systems. Importantly, P-Net also provides interpretable models that can be easily visualized to gain clues about the relationships between patients, and to formulate hypotheses about their stratification.

Authors

  • Jessica Gliozzo
    AnacletoLab - Dipartimento di Informatica, Università degli Studi di Milano, Milan, 20133, Italy.
  • Paolo Perlasca
    AnacletoLab - Dipartimento di Informatica, Università degli Studi di Milano, Milan, 20133, Italy.
  • Marco Mesiti
    AnacletoLab - Dipartimento di Informatica, Università degli Studi di Milano, Milan, 20133, Italy.
  • Elena Casiraghi
    Department of Computer Science "Giovanni degli Antoni,"Università degli Studi di Milano 20133 Milan Italy.
  • Viviana Vallacchi
    Unit of Immunotherapy of Human Tumors, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Elisabetta Vergani
    Unit of Immunotherapy of Human Tumors, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Marco Frasca
    Department of Computer Science "Giovanni degli Antoni,"Università degli Studi di Milano 20133 Milan Italy.
  • Giuliano Grossi
    Department of Computer Science, University of Milan, Via Comelico 39, 20135 Milan, Italy.
  • Alessandro Petrini
    AnacletoLab - Dipartimento di Informatica, Università degli Studi di Milano, Milan, 20133, Italy.
  • Matteo Re
    Anacletolab, Dipartimento di Informatica, Università degli Studi di Milano, Via Comelico 39, 20135, Milan, Italy.
  • Alberto Paccanaro
    Royal Holloway, University of London, Centre for Systems and Synthetic Biology - Department of Computer Science, Egham, TW20 0EX, UK. alberto.paccanaro@rhul.ac.uk.
  • Giorgio Valentini
    Department of Computer Science "Giovanni degli Antoni,"Università degli Studi di Milano 20133 Milan Italy.