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Robust estimation of cancer and immune cell-type proportions from bulk tumor ATAC-Seq data

Published ineLife, vol. 13, RP94833
Publication date2024-10-09
First online date2024-10-09
Abstract

Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) is a widely used technique to explore gene regulatory mechanisms. For most ATAC-Seq data from healthy and diseased tissues such as tumors, chromatin accessibility measurement represents a mixed signal from multiple cell types. In this work, we derive reliable chromatin accessibility marker peaks and reference profiles for most non-malignant cell types frequently observed in the microenvironment of human tumors. We then integrate these data into the EPIC deconvolution framework (Racle et al., 2017) to quantify cell-type heterogeneity in bulk ATAC-Seq data. Our EPIC-ATAC tool accurately predicts non-malignant and malignant cell fractions in tumor samples. When applied to a human breast cancer cohort, EPIC-ATAC accurately infers the immune contexture of the main breast cancer subtypes.

Keywords
  • ATAC-Seq
  • Bulk deconvolution
  • Cancer biology
  • Chromatin accessibility
  • Computational biology
  • Human
  • Systems biology
  • Tumor microenvironment
  • Humans
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Chromatin Immunoprecipitation Sequencing / methods
  • Tumor Microenvironment
  • Female
  • Chromatin / metabolism
  • Chromatin / genetics
  • Neoplasms / genetics
  • Neoplasms / immunology
Citation (ISO format)
GABRIEL, Aurélie Anne-Gaëlle et al. Robust estimation of cancer and immune cell-type proportions from bulk tumor ATAC-Seq data. In: eLife, 2024, vol. 13, p. RP94833. doi: 10.7554/eLife.94833
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Identifiers
Additional URL for this publicationhttps://elifesciences.org/articles/94833
Journal ISSN2050-084X
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