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TUSV-ext: Reconstructing tumor phylogenetic tree with SVs, CNVs and SNVs

This tool aims to deconvolve multi-regional bulk sequencing samples based on variant calls including SVs, SNVs and CNVs and infer a comprehensive tumor phylogenetic tree.

pipeline_diagram

This work is published in Xuecong Fu, Haoyun Lei, Yifeng Tao, Russell Schwartz, Reconstructing tumor clonal lineage trees incorporating single-nucleotide variants, copy number alterations and structural variations, Bioinformatics, Volume 38, Issue Supplement_1, July 2022, Pages i125–i133, https://doi.org/10.1093/bioinformatics/btac253

Requirements

The program is written in Python2. Python3 version will come out soon.

The packages you will need to install are listed below.

  • numpy
  • graphviz
  • ete2
  • biopython
  • gurobipy
  • PyVCF

Gurobi License

To obtain a Gurobi license, you can sign up as an academic user here https://www.gurobi.com/downloads/end-user-license-agreement-academic/ and follow the instructions for downloading a license.

Running

python tusv-ext.py

The script tusv-ext.py takes as input a single directory containing one or multiple .vcf files. Go here https://samtools.github.io/hts-specs/VCFv4.2.pdf for specifications on the .vcf format. Each .vcf file should contain SV breakpoints, CNVs and SNVs with their processed copy numbers from one sample of a patient.

Inputs:

  • -i the input directory containing vcf files of different samples from one patient
  • -o the output directory with deconvoluted results
  • -n number of leaves to infer in phylogenetic tree
  • -c maximum copy number allowed for any breakpoint or segment on any node
  • -t maximum number of coordinate-descent iterations (program can finish sooner if convergence is reached)
  • -r number of random initializations of the coordinate-descent algorithm
  • -col binary flag whether to collapse the redundant nodes
  • -leaf binary flag whether to assume only leaf nodes are in the mixed samples or not
  • -sv_ub approximate maximum number of subsampled breakpoints of structural variants, -1 if you don't want to do the subsampling and include all breakpoints
  • -const maximum number of total subsampled breakpoints and SNVs

The following inputs are optional:

  • -b (recommended) binary flag to automatically set hyper-parameters lambda 1 and lambda 2
  • -l lambda 1 hyper-parameter. controls phylogenetic cost
  • -a lambda 2 hyper-parameter. controls breakpoint to segment consistancy
  • -m maximum time (in seconds) for a single cordinate-descent iteration
  • -s number of segments (in addition to those containing breakpoints) that are randomly kept for unmixing. default keeps all segments
  • -p (not recommended) number of processors to use. uses all available processors by default

Outputs:

  • C.tsv the C matrix which is variants copy number profiles of each clone
  • U.tsv the U matrix which is the frequencies of each clone in each sample
  • T.dot the inferred phylogenetic tree