Delighted to share our latest work with Raghd Rostom, @YuanhuaHuang, @OliverStegle, Sarah Teichmann et al. Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants biorxiv.org/content/early/… 1/9
We leverage and statistically integrate deep exome sequencing data with single-cell RNA sequencing to look at the phenotypic impact of somatic mutations in human fibroblast cells by linking scRNA-seq profiles to inferred clonal cell populations 2/9 
Here, we show that eight of 32 donors have evidence of non-neutral adaptive clonal evolution based on the deep exome data, where the UV mutagenesis signature is the main mutagenic mechanism. 3/9
Even with sparse read coverage of somatic variants in scRNA-seq data we can assign the majority of cells to clones with high accuracy. We can then look at differentially expressed genes and pathways between clones 4/9
For the majority of donors, we identify substantial gene expression differences between clones, and these genes belong to shared pathways across the clones from multiple donors. Proliferation & cell cycle are key pathways that consistently distinguish clones from each other. 5/9
Our cardelino package (github.com/PMBio/cardelino) is generally applicable and could be used to address questions relating to somatic mutations, cell lineaging, ageing and, of course, cancer. 6/9
All code and data are publicly available. Cardelino methods in an open-source R package (github.com/PMBio/cardelino). Reproducible code used to process and analyse the data is available: github.com/davismcc/fibro…. 7/9
Descriptions of how to reproduce the data processing and analysis workflows, w/ html output showing code & all figs presented, available at davismcc.github.io/fibroblast-clo… (thx to @jdblischak's awesome workflowr pkg). Docker images w/ software available too. 8/9
We look forward to feedback. Finally, there was a long-running race to see which would come first: the birth of my first child or completion of the paper. My daughter won! So w/ me on leave, thx to Raghd, Yuanhua and Oli for getting the paper done and ready to share at last! 9/9
