Demo

Follow this link to see a video of the User Interface:

https://drive.google.com/file/d/1cmn083ruUX5KCIYWPqQLlW3a0bgpAm07/view

Installation

Clone and enter this directory, and then:

bash install.sh 
bash build-vue-app.sh

Only installation on Linux x86_64 is currently supported.

Quick Start

Assuming one has access to the protected environment on the CHPC at University of Utah:

bash tests/test.sh

Follow the instructions at the command line to view a web app that visualizes mutation counts as a function of genomic coordinate.

Usage

Assuming that the path to the constraint-tools directory on your filesystem is ${root}, usage is:

PATH="${root}:$PATH"
constraint-tools [SUB_COMMAND] REQUIRED_ARGUMENTS

Valid sub-commands are:

train 
      estimate kmer-dependent mutation probabilities 
visualize
      start a web app that visualizes mutation counts as a function of genomic coordinate
predict
      call genomic regions predicted to be under negative selection [not yet implemented]

Required arguments for train are:

--genome STR
      Path to the reference fasta. 
      A "samtools faidx" index is expected to be present at the same path. 
--region STR 
      Samtools-style specification of a genomic interval (see examples in tests directory).
--mutations STR 
      Path to a set of mutations specified in Mutation Annotation Format.
      A "tabix" index is expected to be present at the same path.
--kmer-size INT
      Size of kmer to use in model. 
--output STR 
      Path to a directory to store results in. 

This produces a specification of the sequence-dependent mutation model in json format, viewable using, e.g.,

${root}/bin/jq . ${output}/<json file> 

Required arguments for visualize are:

--model STR
      Path to the model produced by the train sub-command (in json format)
--port INT 
      The port to serve the web-app on

Input Data

Assuming one has access to the protected environment on the CHPC at University of Utah, then sorted, block-compressed, and indexed vcf, maf, gtf and fasta files can be found at:

/scratch/ucgd/lustre-work/quinlan/u6018199/constraint-tools/data

Development

Changes to the vue-app directory necessitate rebuilding the vue app by running

bash build-vue-app.sh 

Mutation Annotation Format (MAF)

1. specification: https://docs.gdc.cancer.gov/Data/File_Formats/MAF_Format/
2. minimal example: https://github.com/mskcc/vcf2maf/blob/main/data/minimalist_test_maf.tsv
3. tooling:
   1. maf-lib: comprehensive, but lacks so much documentation that it is effectively unusable
   2. vcf2maf: can convert maf to vcf, but reliance on vep makes tool effectively unusable
4. gotchas: https://www.biostars.org/p/69222/