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Deconvolution of heterogeneous tumor samples using partial reference signals.

Yufang Qin1,2, Weiwei Zhang3, Xiaoqiang Sun4

  • 1College of Information Technology, Shanghai Ocean University, Shanghai, China.

Plos Computational Biology
|November 30, 2020
PubMed
Summary
This summary is machine-generated.

PREDE, a novel partial reference-based deconvolution method, accurately estimates cell proportions and profiles in tumor samples. This approach improves the detection of novel cell types and aids in predicting patient survival.

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Area of Science:

  • Computational Biology
  • Bioinformatics
  • Genomics

Background:

  • Deconvoluting heterogeneous bulk tumor samples into distinct cellular populations is crucial but challenging, especially with incomplete cell type references.
  • Existing methods often over-estimate known cell types and miss novel ones when using partial references.

Purpose of the Study:

  • To develop a robust partial reference-based deconvolution method for analyzing heterogeneous tumor samples.
  • To accurately estimate cell proportions and expression profiles, including novel cell types.

Main Methods:

  • Proposed PREDE (Partial Reference-based DEconvolution), an iterative non-negative matrix factorization algorithm.
  • Validated using simulated datasets across various parameter settings.
  • Applied to The Cancer Genome Atlas (TCGA) tumor samples.

Main Results:

  • PREDE effectively estimates cell proportions and expression profiles of both known and unknown cell types.
  • Proportions of pure cancer cells correlate with tumor subtypes.
  • Identified cell types whose proportions predict patient survival.

Conclusions:

  • PREDE offers a significant advancement in deconvoluting heterogeneous tumor samples with partial references.
  • The method has broad applicability to various high-throughput bulk data.
  • PREDE is available as an R package on GitHub.