Cardelino Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants, bioRxiv, 2018-09-12

AbstractDecoding 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 (<jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsgithub.comPMBiocardelino>httpsgithub.comPMBiocardelino<jatsext-link>), 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.Key findings<jatslist list-type=bullet><jatslist-item>A novel approach for integrating DNA-seq and single-cell RNA-seq data to reconstruct clonal substructure for single-cell transcriptomes.<jatslist-item><jatslist-item>Evidence for non-neutral evolution of clonal populations in human fibroblasts.<jatslist-item><jatslist-item>Proliferation and cell cycle pathways are commonly distorted in mutated clonal populations.<jatslist-item>

biorxiv genomics 100-200-users 2018

 

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