Inferring tumour purity and stromal and immune cell admixture from expression data

TLDR

Tumour biopsies contain contaminating stromal and immune cells that constitute a major fraction of normal cells, perturb tumour signals, and influence cancer biology, and an R‑library for analysis is available online. The study develops ESTIMATE, an algorithm that uses gene‑expression signatures from TCGA to infer the fraction of stromal and immune cells contaminating tumour samples. ESTIMATE applies gene‑expression signatures to quantify stromal and immune cell fractions, enabling the inclusion of tumour‑associated normal cells in genomic and transcriptomic analyses. ESTIMATE scores correlate with DNA‑copy‑number–based tumour purity across 11 tumour types and are validated on 3,809 independent transcriptional profiles.

Abstract

Infiltrating stromal and immune cells form the major fraction of normal cells in tumour tissue and not only perturb the tumour signal in molecular studies but also have an important role in cancer biology. Here we describe 'Estimation of STromal and Immune cells in MAlignant Tumours using Expression data' (ESTIMATE)—a method that uses gene expression signatures to infer the fraction of stromal and immune cells in tumour samples. ESTIMATE scores correlate with DNA copy number-based tumour purity across samples from 11 different tumour types, profiled on Agilent, Affymetrix platforms or based on RNA sequencing and available through The Cancer Genome Atlas. The prediction accuracy is further corroborated using 3,809 transcriptional profiles available elsewhere in the public domain. The ESTIMATE method allows consideration of tumour-associated normal cells in genomic and transcriptomic studies. An R-library is available on https://sourceforge.net/projects/estimateproject/ . Tumour biopsies contain contaminating normal cells and these can influence the analysis of tumour samples. In this study, Yoshihara et al.develop an algorithm based on gene expression profiles from The Cancer Genome Atlas to estimate the number of contaminating normal cells in tumour samples.