Create mutation signatures from MAF's, and decompose them into Stratton signatures
You will need the python packages numpy and scipy for anything related to decomposition, and if you want to plot (using plot.py) you will also need matplotlib.
Navigate to the project directory.
The SNPs in your MAF need to be sorted ([1-22, X, Y, M]) and annotated with trinucleotide contexts in a column called Ref_Tri. If this is not already the case, you can use the following command:
python make_trinuc_maf.py <source-maf-path> <target-maf-path>
Next, use the following command, which will (1) Create SNP signatures for samples in the MAF (not saved to disk) (2) Decompose them and write the results to the given path.
python main.py Stratton_signatures.txt <maf-file-path> <decomposed-output-file-path>
In order to use this, you need the following columns in your MAF:
"Tumor_Sample_Barcode", "Reference_Allele", "Variant_Type", "Tumor_Seq_Allele2", "Ref_Tri"
You may use, for example, python main.py --seed 100 for a reproducible result.
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Resample each Tumor_Sample_Barcode in a maf file (with replacement) 1000 times, thusly:
./sigsig.R input.maf 1000 input.resamp.maf
Alternatively you can opt to split the output maf file by Tumor_Sample_Barcode with a 4th argument split:
./sigsig.R input.maf 1000 input_resamp_maf/ split
Note that the original maf is included at the top of the resampled file. Resamples get :1, :2, etc. at the end of the Tumor_Sample Barcode.
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Run decomposition as usual:
python main.py Stratton_signatures30.txt input.resamp.maf input.resamp.sig.txt
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Calculate the (1 s.d.) confidence intervals and a quasi-pvalue for each signature:
./sigsig_conf_int.R input.resamp.sig.txt input.resamp.sig.conf_int.txt
Decompsed signatures without :1, :2, etc. at the end will appear as observed_val.
Example output:
| Tumor_Sample_Barcode | Signature | observed_val | lower_val | median_val | upper_val | quasi_pvalue |
|---|---|---|---|---|---|---|
| TCGA-05-4249 | 1 | 0.10231 | 0.013611 | 0.08426 | 0.13959 | 0.12098 |
| TCGA-05-4249 | 2 | 2.953e-08 | 1.015e-11 | 2.709e-07 | 0.018698 | 0.50322 |
| TCGA-05-4249 | 3 | 1.912e-10 | 1.131e-11 | 3.392e-10 | 5.492e-07 | 0.84942 |
| TCGA-05-4249 | 4 | 0.38532 | 0.27567 | 0.37571 | 0.46896 | 0 |
| TCGA-05-4249 | 5 | 3.432e-9 | 9.335e-12 | 3.725e-10 | 7.171e-09 | 0.95238 |
Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Campbell, P. J., & Stratton, M. R. (2013). Deciphering Signatures of Mutational Processes Operative in Human Cancer. Cell Reports, 3(1), 246–259. doi:10.1016/j.celrep.2012.12.008