TY  - JOUR
KW  - Gene expression
KW  -  Mutation
KW  -  Statistical methods
ID  - discovery10103579
EP  - 421
N2  - Bulk and single-cell DNA sequencing has enabled reconstructing clonal substructures of somatic tissues from frequency and cooccurrence patterns of somatic variants. However, approaches to characterize phenotypic variations between clones are not established. Here we present cardelino (https://github.com/single-cell-genetics/cardelino), a computational method for inferring the clonal tree configuration and the clone of origin of individual cells assayed using single-cell RNA-seq (scRNA-seq). Cardelino flexibly integrates information from imperfect clonal trees inferred based on bulk exome-seq data, and sparse variant alleles expressed in scRNA-seq data. We apply cardelino to a published cancer dataset and to newly generated matched scRNA-seq and exome-seq 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 role for cell division genes in somatic evolution in healthy skin.
AV  - public
JF  - Nature Methods
VL  - 17
UR  - https://doi.org/10.1038/s41592-020-0766-3
A1  - McCarthy, DJ
A1  - Rostom, R
A1  - Huang, Y
A1  - Kunz, DJ
A1  - Danecek, P
A1  - Bonder, MJ
A1  - Hagai, T
A1  - Lyu, R
A1  - HipSci Consortium
A1  - Wang, W
A1  - Gaffney, DJ
A1  - Simons, BD
A1  - Stegle, O
A1  - Teichmann, SA
Y1  - 2020/04//
TI  - Cardelino: computational integration of somatic clonal substructure and single-cell transcriptomes
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
SP  - 414
ER  -