eLife (Oct 2024)

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

  • Aurélie Anne-Gaëlle Gabriel,
  • Julien Racle,
  • Maryline Falquet,
  • Camilla Jandus,
  • David Gfeller

DOI
https://doi.org/10.7554/eLife.94833
Journal volume & issue
Vol. 13

Abstract

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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.

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