netDx: interpretable patient classification using integrated patient similarity networks

Mol Syst Biol. 2019 Mar 14;15(3):e8497. doi: 10.15252/msb.20188497.

Abstract

Patient classification has widespread biomedical and clinical applications, including diagnosis, prognosis, and treatment response prediction. A clinically useful prediction algorithm should be accurate, generalizable, be able to integrate diverse data types, and handle sparse data. A clinical predictor based on genomic data needs to be interpretable to drive hypothesis-driven research into new treatments. We describe netDx, a novel supervised patient classification framework based on patient similarity networks, which meets these criteria. In a cancer survival benchmark dataset integrating up to six data types in four cancer types, netDx significantly outperforms most other machine-learning approaches across most cancer types. Compared to traditional machine-learning-based patient classifiers, netDx results are more interpretable, visualizing the decision boundary in the context of patient similarity space. When patient similarity is defined by pathway-level gene expression, netDx identifies biological pathways important for outcome prediction, as demonstrated in breast cancer and asthma. netDx can serve as a patient classifier and as a tool for discovery of biological features characteristic of disease. We provide a free software implementation of netDx with automation workflows.

Keywords: multimodal data integration; multi‐omics; patient similarity networks; precision medicine; supervised machine learning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Asthma / classification*
  • Asthma / diagnosis
  • Asthma / genetics
  • Benchmarking
  • Breast Neoplasms / classification*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Female
  • Genomics
  • Humans
  • Machine Learning*
  • Prognosis
  • Software*
  • Survival Analysis
  • Workflow