Human dermal fibroblast clonality project

Last updated: 2018-08-24

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Project overview

This project investigates clonality in human dermal fibroblast cell populations in 32 cell lines from distinct donors, using bulk whole-exome sequencing and single-cell RNA-sequencing data.

Key findings:

A novel approach for integrating DNA-seq and single-cell RNA-seq data to reconstruct clonal substructure and single-cell transcriptomes.
A new computational method, cardelino, to map single-cell RNA-seq profiles to clones.
Evidence for non-neutral evolution of clonal populations in human fibroblasts.
Proliferation and cell cycle pathways are commonly distorted in mutated clonal populations, with implications for cancer and ageing.

For a richer overview, see the About page.

Data availability

Single-cell RNA-seq data have been deposited in the ArrayExpress database at EMBL-EBI under accession number E-MTAB-7167. Whole-exome sequencing data is available through the HipSci portal. Processed data and large results files are available at …

Data pre-processing

The data pre-processing for this project from the raw data described above is complicated and computationally expensive, so this repository does not reproduce the data pre-processing in an automated way. However, we provide the source code for the Snakemake workflow for data pre-processing in this repository. Docker images providing the computing environment and software used are publicly available, split into an image for command line bioinformatics tools and an R installation with necessary packages installed.

If you would like to pre-process the data from raw reads to results as we have, please consult our description of how to run the workflow.

Analyses

Here we present the reproducible the results of our analyses. They were generated by rendering the R Markdown documents into webpages available at the links below.

The results presented in the paper were produced with these analyses.

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

This reproducible R Markdown analysis was created with workflowr 1.1.1

Human dermal fibroblast clonality project

Davis J. McCarthy

Project overview

Data availability

Data pre-processing

Analyses