Protocol for interpretable and context-specific single-cell-informed deconvolution of bulk RNA-seq data

STAR Protoc. 2025 Mar 21;6(1):103670. doi: 10.1016/j.xpro.2025.103670. Epub 2025 Mar 4.

Abstract

Single-cell sequencing provides rich information; however, its clinical use is limited due to high costs and complex data output. Here, we present a protocol for extracting single-cell-related information from bulk RNA-sequencing (RNA-seq) data using the pathway-level information extractor (PLIER) algorithm. We describe the steps for extracting single-cell signatures from literature, training a PLIER model based on single-cell signatures (named CLIER), and applying it to a new dataset. This produces latent variables that are interpretable in the context of specific single-cell biology. For complete details on the use and execution of this protocol, please refer to Legouis et al.,1 where this approach is used within the renal context.

Keywords: Bioinformatics; RNA-seq; Single Cell.

MeSH terms

  • Algorithms
  • Computational Biology / methods
  • Humans
  • RNA-Seq* / methods
  • Sequence Analysis, RNA* / methods
  • Single-Cell Analysis* / methods