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.\"
.IX Title "GMT-MUSIC-SMG 1p"
.TH GMT-MUSIC-SMG 1p "2018-07-05" "perl v5.26.2" "User Contributed Perl Documentation"
.\" For nroff, turn off justification.  Always turn off hyphenation; it makes
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.nh
.SH "gmt music smg"
.IX Header "gmt music smg"
.SH "NAME"
gmt music smg \- Identify significantly mutated genes.
.SH "VERSION"
.IX Header "VERSION"
This document describes gmt music smg version 0.04 (2018\-07\-05 at 09:17:13)
.SH "SYNOPSIS"
.IX Header "SYNOPSIS"
gmt music smg \-\-gene\-mr\-file=? \-\-output\-file=? [\-\-max\-fdr=?] [\-\-skip\-low\-mr\-genes] [\-\-bmr\-modifier\-file=?] [\-\-processors=?]
.PP
.Vb 3
\& ... music smg \e
\&      \-\-gene\-mr\-file output_dir/gene_mrs \e
\&      \-\-output\-file output_dir/smgs
.Ve
.PP
(A \*(L"gene-mr-file\*(R" can be generated using the tool \*(L"music bmr calc-bmr\*(R".)
.SH "REQUIRED ARGUMENTS"
.IX Header "REQUIRED ARGUMENTS"
.IP "gene-mr-file  \fIText\fR" 4
.IX Item "gene-mr-file Text"
File with per-gene mutation rates (Created using \*(L"music bmr calc-bmr\*(R")
.IP "output-file  \fIText\fR" 4
.IX Item "output-file Text"
Output file that will list significantly mutated genes and their p\-values
.SH "OPTIONAL ARGUMENTS"
.IX Header "OPTIONAL ARGUMENTS"
.IP "max-fdr  \fINumber\fR" 4
.IX Item "max-fdr Number"
The maximum allowed false discovery rate for a gene to be considered an \s-1SMG\s0
.Sp
Default value '0.2' if not specified
.IP "skip-low-mr-genes  \fIBoolean\fR" 4
.IX Item "skip-low-mr-genes Boolean"
Skip testing genes with MRs lower than the background \s-1MR\s0
.Sp
Default value 'true' if not specified
.IP "noskip-low-mr-genes  \fIBoolean\fR" 4
.IX Item "noskip-low-mr-genes Boolean"
Make skip-low-mr-genes 'false'
.IP "bmr-modifier-file  \fIText\fR" 4
.IX Item "bmr-modifier-file Text"
Tab delimited multipliers per gene that modify \s-1BMR\s0 before testing [gene_name bmr_modifier]
.IP "processors  \fIInteger\fR" 4
.IX Item "processors Integer"
Number of processors to use (requires 'foreach' and 'doMC' R packages)
.Sp
Default value '1' if not specified
.SH "DESCRIPTION"
.IX Header "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 \*(L"music bmr calc-bmr\*(R").
.PP
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 (\s-1FCPT\s0), Likelihood Ratio test (\s-1LRT\s0), and the Convolution
test (\s-1CT\s0). For a gene, if its \s-1FDR\s0 for at least 2 of these tests is <= max_fdr, it will be output
as an \s-1SMG.\s0 Another output file with prefix \*(L"_detailed\*(R" will have p\-values and FDRs for all genes.
.SH "ARGUMENTS"
.IX Header "ARGUMENTS"
.IP "\-\-bmr\-modifier\-file" 4
.IX Item "--bmr-modifier-file"
.RS 4
.PD 0
.IP "The user can provide a \s-1BMR\s0 modifier for each gene in the \s-1ROI\s0 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 \s-1DNA\s0 repair processes like transcription-coupled repair or mismatch repair. Mutation rates have also been associated with \s-1DNA\s0 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 \s-1BMR.\s0 Any genes from the \s-1ROI\s0 file that are not in the \s-1BMR\s0 modifier file will be tested against unmodified overall BMRs per mutation category. \s-1BMR\s0 modifiers of <=0 are not permitted, because that's just silly." 8
.IX Item "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."
.RE
.RS 4
.RE
.IP "\-\-skip\-low\-mr\-genes" 4
.IX Item "--skip-low-mr-genes"
.RS 4
.IP "Genes with consistently lower MRs than the BMRs across mutation categories, may show up in the results as an \s-1SMG\s0 (by \s-1CT\s0 or \s-1LRT\s0). 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 \s-1MR\s0 is lower than the \s-1BMR.\s0 If bmr-modifiers are applied, this step uses the modified BMRs instead." 8
.IX Item "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."
.RE
.RS 4
.RE
.PD
.SH "AUTHORS"
.IX Header "AUTHORS"
.Vb 3
\& Qunyuan Zhang, Ph.D.
\& Cyriac Kandoth, Ph.D.
\& Nathan D. Dees, Ph.D.
.Ve