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Cardelino: computational integration of somatic clonal substructure and single-cell transcriptomes.

Davis J McCarthy^1,2,3, Raghd Rostom^1,4, Yuanhua Huang^1,5

¹European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK.

|March 24, 2020

Summary

This summary is machine-generated.

A new computational method, cardelino, reconstructs cell lineages and identifies phenotypic differences between somatic clones using DNA and single-cell RNA sequencing. This reveals cell division genes are key drivers in the somatic evolution of healthy skin.

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Area of Science:

Genomics
Computational Biology
Cancer Research

Background:

Bulk and single-cell DNA sequencing allow reconstruction of somatic tissue clonal substructures.
Methods to characterize phenotypic variations between clones are lacking.

Purpose of the Study:

Introduce cardelino, a computational method for inferring clonal tree configuration and cell-specific clone origins.
Integrate bulk exome-seq and single-cell RNA-seq (scRNA-seq) data for robust clonal analysis.

Main Methods:

Cardelino integrates imperfect clonal trees from bulk exome-seq with sparse variant alleles from scRNA-seq.
The method was applied to a cancer dataset and new data from 32 human dermal fibroblast lines.

Main Results:

Hundreds of differentially expressed genes were identified between cells from different somatic clones.
Enrichment analysis revealed cell cycle and proliferation pathways were frequently affected.

Conclusions:

Cardelino enables characterization of phenotypic variations between somatic clones.
Cell division genes play a significant role in the somatic evolution of healthy skin.