genome music smg¶
NAME¶
genome music smg - Identify significantly mutated genes.
VERSION¶
This document describes genome music smg version 0.04 (2013-05-14 at 16:03:04)
SYNOPSIS¶
genome music smg --gene-mr-file=? --output-file=? [--max-fdr=?]
[--skip-low-mr-genes] [--bmr-modifier-file=?] [--processors=?]
... music smg \
--gene-mr-file output_dir/gene_mrs \
--output-file output_dir/smgs
(A "gene-mr-file" can be generated using the tool "music bmr
calc-bmr".)
REQUIRED ARGUMENTS¶
- gene-mr-file Text
- File with per-gene mutation rates (Created using "music bmr
calc-bmr")
- output-file Text
- Output file that will list significantly mutated genes and their
p-values
OPTIONAL ARGUMENTS¶
- max-fdr Number
- The maximum allowed false discovery rate for a gene to be considered an
SMG
Default value '0.2' if not specified
- skip-low-mr-genes Boolean
- Skip testing genes with MRs lower than the background MR
Default value 'true' if not specified
- bmr-modifier-file Text
- Tab delimited multipliers per gene that modify BMR before testing
[gene_name bmr_modifier]
- processors Integer
- Number of processors to use (requires 'foreach' and 'doMC' R packages)
Default value '1' if not specified
DESCRIPTION¶
This script runs R-based statistical tools to identify Significantly Mutated
Genes (SMGs), when given per-gene mutation rates categorized by mutation type,
and the overall background mutation rates (BMRs) for each of those categories
(gene_mr_file, created using "music bmr calc-bmr").
P-values and false discovery rates (FDRs) for each gene in gene_mr_file is
calculated using three tests: Fisher's Combined P-value test (FCPT),
Likelihood Ratio test (LRT), and the Convolution test (CT). For a gene, if its
FDR for at least 2 of these tests is <= max_fdr, it will be output as an
SMG. Another output file with prefix "_detailed" will have p-values
and FDRs for all genes.
ARGUMENTS¶
- --bmr-modifier-file
- The user can provide a BMR modifier for each gene in the ROI file, which
is a multiplier for the categorized background mutation rates, before
testing them against the gene's categorized mutation rates. Such a file can
be used to correct for regional or systematic bias in mutation rates across
the genome that may be correlated to CpG deamination or DNA repair processes
like transcription-coupled repair or mismatch repair. Mutation rates have
also been associated with DNA replication timing, where higher mutation
rates are seen in late replicating regions. Note that the same per-gene
multiplier is used on each mutation category of BMR. Any genes from the ROI
file that are not in the BMR modifier file will be tested against unmodified
overall BMRs per mutation category. BMR modifiers of <=0 are not
permitted, because that's just silly.
- --skip-low-mr-genes
- Genes with consistently lower MRs than the BMRs across mutation
categories, may show up in the results as an SMG (by CT or LRT). If such
genes are not of interest, they may be assigned a p-value of 1. This should
also speed things up. Genes with higher Indel or Truncation rates than the
background will not be skipped even if the gene's overall MR is lower than
the BMR. If bmr-modifiers are applied, this step uses the modified BMRs
instead.
AUTHORS¶
Qunyuan Zhang, Ph.D.
Cyriac Kandoth, Ph.D.
Nathan D. Dees, Ph.D.
