Data-driven identification of prognostic tumor subpopulations using spatially mapped t-SNE of mass spectrometry imaging data

Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12244-12249. doi: 10.1073/pnas.1510227113. Epub 2016 Oct 10.

Abstract

The identification of tumor subpopulations that adversely affect patient outcomes is essential for a more targeted investigation into how tumors develop detrimental phenotypes, as well as for personalized therapy. Mass spectrometry imaging has demonstrated the ability to uncover molecular intratumor heterogeneity. The challenge has been to conduct an objective analysis of the resulting data to identify those tumor subpopulations that affect patient outcome. Here we introduce spatially mapped t-distributed stochastic neighbor embedding (t-SNE), a nonlinear visualization of the data that is able to better resolve the biomolecular intratumor heterogeneity. In an unbiased manner, t-SNE can uncover tumor subpopulations that are statistically linked to patient survival in gastric cancer and metastasis status in primary tumors of breast cancer.

Keywords: biomarker; cancer; intratumor heterogeneity; mass spectrometry imaging; t-SNE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Lineage / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Variation*
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Precision Medicine
  • Prognosis*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Survival Analysis

Substances

  • Biomarkers, Tumor