doubleTime is a method to estimate the timing of whole-genome doubling event(s) on a clone tree using SNVs. The current doubleTree software is designed for DLP+ single-cell whole-genome sequencing data.
doubleTime consists of the following steps:
- Construct clone tree from SBMClone output using the perfect phylogeny algorithm.
- Construct clone copy-number profiles and summarize SNV-covering reads at the clone level.
- Assign SNVs to branches of the tree.
Coming soon:
- Apply a statistical test to estimate the number of WGD events affecting the tree.
- Correct branch lengths for variable SNV discovery in clones consisting of different numbers of cells.
- Single-cell haplotype-specific copy-number calls
- Counts for the number of SNV-covering and SNV-supporting reads in each cell for each SNV
- SBMClone results to group cells into clones
- Reference genome that was used for SNV and CNA analysis (FASTA file)
See demo/input for examples.
doubleTime produces output files with the following suffixes (prefix is the patient name):
_annotated_tree.pickle: Clone tree with WGD events assigned to branches and SNV-derived branch lengths_cna_clustered.h5/_snv_clustered.h5: Clustered anndatas representing aggregate copy-number calls and SNV counts at the clone level_tree_snv_assignment.csv: Table containing SNV metrics and assignments to branches of the tree
An intermediate tree without annotations (_tree.pickle) is also produced and can be safely ignored or deleted.
See demo/output for examples.
- Clone this repository
- Install dependencies from
environment.yml:conda create -n doubletime --file environment.yml
Optional: to run the demo, you will need to point demo.yaml to the reference genome GRCh37-lite.fa, which can be found here: https://www.bcgsc.ca/downloads/genomes/9606/hg19/1000genomes/bwa_ind/genome/GRCh37-lite.fa
snakemake --snakefile doubleTime.smk --configfile demo.yaml
Running doubleTree on the input data in demo/input should produce the output files in demo/output.