genome music smg

NAME

       genome music smg - Identify significantly mutated genes.

VERSION

       This document describes genome music smg version 0.04 (2018-07-05 at 09:17:13)

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

       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.