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Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants
Daniel J Kunz,
Marc Jan Bonder,
Daniel J Gaffney,
Benjamin D Simons,
Sarah A Teichmann
Posted 10 Sep 2018
bioRxiv DOI: 10.1101/413047
Posted 10 Sep 2018
Decoding the clonal substructures of somatic tissues sheds light on cell growth, development and differentiation in health, ageing and disease. DNA-sequencing, either using bulk or using single-cell assays, has enabled the reconstruction of clonal trees from frequency and co-occurrence patterns of somatic variants. However, approaches to systematically characterize phenotypic and functional variations between individual clones are not established. Here we present cardelino (https://github.com/PMBio/cardelino), a computational method for inferring the clone of origin of individual cells that have been assayed using single-cell RNA-seq (scRNA-seq). After validating our model using simulations, we apply cardelino to matched scRNA-seq and exome sequencing data from 32 human dermal fibroblast lines, identifying hundreds of differentially expressed genes between cells from different somatic clones. These genes are frequently enriched for cell cycle and proliferation pathways, indicating a key role for cell division genes in non-neutral somatic evolution.
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