Readme.md

Usage

Calculate somatic TMB (non-synonymous) of all sequenced samples for a specific study. TMB is the total number of non-synonymous, somatic mutations identified per megabase (Mb) of the genome coding area of DNA (a megabase is 1,000,000 DNA basepairs)

Method

Step 1: Calculate Total number N of non-synonymous, somatic mutations with eligible classification (list below) in MAF

	"Frame_Shift_Del"
	"Frame_Shift_Ins" 
	"In_Frame_Del" 
	"In_Frame_Ins" 
	"Missense_Mutation" 
	"Nonsense_Mutation" 
	"Splice_Site"
	"Nonstop_Mutation" 
	"Splice_Region"

Step 2: Determine the size L of genome coding area of DNA in megabase(Mb)

• For WES/WGS: L = 30
• For targeted sequenced: refer to the CDS field in related gene panel files (need to be divided by 1M) ** CDS field is calculated by this script

Step 3: Calculate TMB for each sequenced sample

TMB = N/L

• For sequenced sample: if used panel size is <0.2M, the TMB is not calculated and marked as "NA"
• For not sequenced samples (refer to cases_sequenced.txt for each study), the TMB is marked as "NA"

Step 4: Append TMB scores as an additional column in sample clinical file.

Command Line

Usage: calc_nonsyn_tmb.py [-h] -i INPUT_STUDY_FOLDER -p
                          INPUT_GENE_PANEL_FOLDER

optional arguments:
  -h, --help            show this help message and exit
  -i INPUT_STUDY_FOLDER, --input-study-folder INPUT_STUDY_FOLDER
                        Input Study folder
  -p INPUT_GENE_PANEL_FOLDER, --input-gene-panel-folder INPUT_GENE_PANEL_FOLDER
                        Gene Panel folder

Example

python path/to/calc_nonsyn_tmb.py -p path/to/gene_panels -i path/to/study

Notes

For WGS and WES studies, the gene panel folder parameter is still needed.