REVMUT can help to find and verify putative revertant mutations (PRMs) in DNA sequence data. Common workflow is:
There are scripts to do 1 and 3. Steps 2 might be added at a later stage in development.
.. image:: img/revmut_overview.png
::
pip install revmut
The finding module takes a mutation and finds PRMs that:
Delete the entire given mutation
Restore the reading frame in case the given mutation (GM) is an indel. The criterium is::
length(PRM) +/- length(GM) % 3 == 0
Run with::
revmut-find tests/test_data/human_g1k_v37_chr17.fa tests/test_data/germline_mutations/T1_test_mutation.tsv tests/test_data/T1.bam tests/test_data/N1.bam > tests/test_data/output/T1_test.tsv
View input/output files:
tests/test_data/germline_mutations/T1_test_mutation.tsv <tests/test_data/germline_mutations/T1_test_mutation.tsv>
_tests/test_data/output/T1_test.tsv <tests/test_data/output/T1_test.tsv>
_Annotation of the PRMs is currently done semi-manually with Oncotator webserice <http://www.broadinstitute.org/oncotator/>
_. Perhaps at a later stage in development this will be done automatically. Missing is a VCF to Oncotator format converter.
Applies a given mutation in cDNA format to a transcript followed by the cDNA change of the PRM as predicted by Oncotator. Output gives a prediction of how the protein changes.
Run with::
revmut-verify tests/test_data/to_be_reverted_mutations.txt tests/test_data/oncotator.ins.txt tests/test_data/BRCA_transcripts.fa > tests/test_data/oncotator.ins.maf.out.tsv
View input/output files:
tests/test_data/to_be_reverted_mutations.txt <tests/test_data/to_be_reverted_mutations.txt>
_tests/test_data/oncotator.ins.txt <tests/test_data/oncotator.ins.txt>
_tests/test_data/output/oncotator.ins.maf.out.tsv <tests/test_data/output/oncotator.ins.maf.out.tsv>
_For an example that includes only reversion mutations try these BRCA1 mutations from the paper Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer.::
revmut-verify tests/test_data/paper/brca1/to_be_reverted_mutations.txt tests/test_data/paper/brca1/oncotator.ins.txt tests/test_data/BRCA_transcripts.fa > tests/test_data/paper/brca1/output/oncotator.ins.maf.out.tsv
View input/output files:
tests/test_data/paper/brca1/to_be_reverted_mutations.txt <tests/test_data/paper/brca1/to_be_reverted_mutations.txt>
_tests/test_data/paper/brca1/oncotator.ins.txt <tests/test_data/paper/brca1/oncotator.ins.txt>
_tests/test_data/paper/brca1/output/oncotator.ins.maf.out.tsv <tests/test_data/paper/brca1/output/oncotator.ins.maf.out.tsv>
_A description of the columns in the output format::
mut = germline mutation
revmut = potential revertant mutation
revmut_pos_adj = the adjusted revertant mutations position after the germline mutation has been applied
transcript = the transcript to apply the cdna change to
normal_protein_length = the length of the protein when you translate the transcript in amino acids
mut_protein_length = how long the protein is after applying the germline mut cdna change and translating
revmut_protein_length = how long the protein is after applying the germline mut cdna change followed by the potential revertant mutation cdna change and translating
mut_p_distance = number of amino acids that differ between original protein and germline mutated protein
revmut_p_distance = number of amino acids that differ between original protein and germline + revertant mutated protein
Tests
In root dir run::
nosetests