ADAPTS: Automated deconvolution augmentation of profiles for tissue specific cells

PLoS One. 2019 Nov 19;14(11):e0224693. doi: 10.1371/journal.pone.0224693. eCollection 2019.

Abstract

Immune cell infiltration of tumors and the tumor microenvironment can be an important component for determining patient outcomes. For example, immune and stromal cell presence inferred by deconvolving patient gene expression data may help identify high risk patients or suggest a course of treatment. One particularly powerful family of deconvolution techniques uses signature matrices of genes that uniquely identify each cell type as determined from single cell type purified gene expression data. Many methods from this family have been recently published, often including new signature matrices appropriate for a single purpose, such as investigating a specific type of tumor. The package ADAPTS helps users make the most of this expanding knowledge base by introducing a framework for cell type deconvolution. ADAPTS implements modular tools for customizing signature matrices for new tissue types by adding custom cell types or building new matrices de novo, including from single cell RNAseq data. It includes a common interface to several popular deconvolution algorithms that use a signature matrix to estimate the proportion of cell types present in heterogenous samples. ADAPTS also implements a novel method for clustering cell types into groups that are difficult to distinguish by deconvolution and then re-splitting those clusters using hierarchical deconvolution. We demonstrate that the techniques implemented in ADAPTS improve the ability to reconstruct the cell types present in a single cell RNAseq data set in a blind predictive analysis. ADAPTS is currently available for use in R on CRAN and GitHub.

Publication types

  • Evaluation Study

MeSH terms

  • Cluster Analysis
  • Computational Biology / methods*
  • Datasets as Topic
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • RNA-Seq / methods*
  • Single-Cell Analysis / methods*
  • Software*
  • Support Vector Machine
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Grants and funding

This work was supported by Institute for Systems Biology. The funder provided support in the form of salaries for authors DLG and IS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This work was supported by Celgene Corporation. The funder provided support in the form of salaries for authors SAD, MM, MWBT, FS, DJR and AVR, but did not have any additional role in the study design, data collection and analysis, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Celgene Corporation approved the authors’ decision to publish after an internal intellectual property review.