BMC Bioinformatics (Nov 2023)

scMuffin: an R package to disentangle solid tumor heterogeneity by single-cell gene expression analysis

  • Valentina Nale,
  • Alice Chiodi,
  • Noemi Di Nanni,
  • Ingrid Cifola,
  • Marco Moscatelli,
  • Cinzia Cocola,
  • Matteo Gnocchi,
  • Eleonora Piscitelli,
  • Ada Sula,
  • Ileana Zucchi,
  • Rolland Reinbold,
  • Luciano Milanesi,
  • Alessandra Mezzelani,
  • Paride Pelucchi,
  • Ettore Mosca

DOI
https://doi.org/10.1186/s12859-023-05563-y
Journal volume & issue
Vol. 24, no. 1
pp. 1 – 18

Abstract

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Abstract Introduction Single-cell (SC) gene expression analysis is crucial to dissect the complex cellular heterogeneity of solid tumors, which is one of the main obstacles for the development of effective cancer treatments. Such tumors typically contain a mixture of cells with aberrant genomic and transcriptomic profiles affecting specific sub-populations that might have a pivotal role in cancer progression, whose identification eludes bulk RNA-sequencing approaches. We present scMuffin, an R package that enables the characterization of cell identity in solid tumors on the basis of a various and complementary analyses on SC gene expression data. Results scMuffin provides a series of functions to calculate qualitative and quantitative scores, such as: expression of marker sets for normal and tumor conditions, pathway activity, cell state trajectories, Copy Number Variations, transcriptional complexity and proliferation state. Thus, scMuffin facilitates the combination of various evidences that can be used to distinguish normal and tumoral cells, define cell identities, cluster cells in different ways, link genomic aberrations to phenotypes and identify subtle differences between cell subtypes or cell states. We analysed public SC expression datasets of human high-grade gliomas as a proof-of-concept to show the value of scMuffin and illustrate its user interface. Nevertheless, these analyses lead to interesting findings, which suggest that some chromosomal amplifications might underlie the invasive tumor phenotype and the presence of cells that possess tumor initiating cells characteristics. Conclusions The analyses offered by scMuffin and the results achieved in the case study show that our tool helps addressing the main challenges in the bioinformatics analysis of SC expression data from solid tumors.

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