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PROGRAM:

NAME


gmt music smg - Identify significantly mutated genes.

VERSION


This document describes gmt music smg version 0.04 (2016-01-01 at 23:10:18)

SYNOPSIS


gmt 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

noskip-low-mr-genes Boolean
Make skip-low-mr-genes 'false'

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.

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