Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

. 2022 Sep 23;2(11):100179. doi: 10.1016/j.xgen.2022.100179

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Deposited data

PCAWG and extended dataset	263 published studies and 35 ICGC projects⁶^,⁴³^,⁴⁹^,⁵¹^,⁵⁹^,⁶⁰^,⁶¹^,⁶²^,⁶³^,⁶⁴^,⁶⁵^,⁶⁶^,⁶⁷^,⁶⁸^,⁶⁹^,⁷⁰^,⁷¹^,⁷²^,⁷³^,⁷⁴^,⁷⁵^,⁷⁶^,⁷⁷^,⁷⁸^,⁷⁹^,⁸⁰^,⁸¹^,⁸²^,⁸³^,⁸⁴^,⁸⁵^,⁸⁶^,⁸⁷^,⁸⁸^,⁸⁹^,⁹⁰^,⁹¹^,⁹²^,⁹³^,⁹⁴^,⁹⁵^,⁹⁶^,⁹⁷^,⁹⁸^,⁹⁹^,¹⁰⁰^,¹⁰¹^,¹⁰²^,¹⁰³^,¹⁰⁴^,¹⁰⁵^,¹⁰⁶^,¹⁰⁷^,¹⁰⁸^,¹⁰⁹^,¹¹⁰^,¹¹¹^,¹¹²^,¹¹³^,¹¹⁴^,¹¹⁵^,¹¹⁶^,¹¹⁷^,¹¹⁸^,¹¹⁹^,¹²⁰^,¹²¹^,¹²²^,¹²³^,¹²⁴^,¹²⁵^,¹²⁶^,¹²⁷^,¹²⁸^,¹²⁹^,¹³⁰^,¹³¹^,¹³²^,¹³³^,¹³⁴^,¹³⁵^,¹³⁶^,¹³⁷^,¹³⁸^,¹³⁹^,¹⁴⁰^,¹⁴¹^,¹⁴²^,¹⁴³^,¹⁴⁴^,¹⁴⁵^,¹⁴⁶^,¹⁴⁷^,¹⁴⁸^,¹⁴⁹^,¹⁵⁰^,¹⁵¹^,¹⁵²^,¹⁵³^,¹⁵⁴^,¹⁵⁵^,¹⁵⁶^,¹⁵⁷^,¹⁵⁸^,¹⁵⁹^,¹⁶⁰^,¹⁶¹^,¹⁶²^,¹⁶³^,¹⁶⁴^,¹⁶⁵^,¹⁶⁶^,¹⁶⁷^,¹⁶⁸^,¹⁶⁹^,¹⁷⁰^,¹⁷¹^,¹⁷²^,¹⁷³^,¹⁷⁴^,¹⁷⁵^,¹⁷⁶^,¹⁷⁷^,¹⁷⁸^,¹⁷⁹^,¹⁸⁰^,¹⁸¹^,¹⁸²^,¹⁸³^,¹⁸⁴^,¹⁸⁵^,¹⁸⁶^,¹⁸⁷^,¹⁸⁸^,¹⁸⁹^,¹⁹⁰^,¹⁹¹^,¹⁹²^,¹⁹³^,¹⁹⁴^,¹⁹⁵^,¹⁹⁶^,¹⁹⁷^,¹⁹⁸^,¹⁹⁹^,²⁰⁰^,²⁰¹^,²⁰²^,²⁰³^,²⁰⁴^,²⁰⁵^,²⁰⁶^,²⁰⁷^,²⁰⁸^,²⁰⁹^,²¹⁰^,²¹¹^,²¹²^,²¹³^,²¹⁴^,²¹⁵^,²¹⁶^,²¹⁷^,²¹⁸^,²¹⁹^,²²⁰^,²²¹^,²²²^,²²³^,²²⁴^,²²⁵^,²²⁶^,²²⁷^,²²⁸^,²²⁹^,²³⁰^,²³¹^,²³²^,²³³^,²³⁴^,²³⁵^,²³⁶^,²³⁷^,²³⁸^,²³⁹^,²⁴⁰^,²⁴¹^,²⁴²^,²⁴³^,²⁴⁴^,²⁴⁵^,²⁴⁶^,²⁴⁷^,²⁴⁸^,²⁴⁹^,²⁵⁰^,²⁵¹^,²⁵²^,²⁵³^,²⁵⁴^,²⁵⁵^,²⁵⁶^,²⁵⁷^,²⁵⁸^,²⁵⁹^,²⁶⁰^,²⁶¹^,²⁶²^,²⁶³^,²⁶⁴^,²⁶⁵^,²⁶⁶^,²⁶⁷^,²⁶⁸^,²⁶⁹^,²⁷⁰^,²⁷¹^,²⁷²^,²⁷³^,²⁷⁴^,²⁷⁵^,²⁷⁶^,²⁷⁷^,²⁷⁸^,²⁷⁹^,²⁸⁰^,²⁸¹^,²⁸²^,²⁸³^,²⁸⁴^,²⁸⁵^,²⁸⁶^,²⁸⁷^,²⁸⁸^,²⁸⁹^,²⁹⁰^,²⁹¹^,²⁹²^,²⁹³^,²⁹⁴^,²⁹⁵^,²⁹⁶^,²⁹⁷^,²⁹⁸^,²⁹⁹^,³⁰⁰^,³⁰¹^,³⁰²^,³⁰³^,³⁰⁴^,³⁰⁵^,³⁰⁶^,³⁰⁷^,³⁰⁸^,³⁰⁹^,³¹⁰^,³¹¹^,³¹²^,³¹³^,³¹⁴^,³¹⁵^,³¹⁶^,³¹⁷^,³¹⁸^,³¹⁹^,³²⁰^,³²¹^,³²²	Table S8
Normal urothelium dataset	Lawson et al., 2020⁵⁰	EGA: EGAD00001006113 and EGAD00001006116
Bladder urothelial carcinoma dataset	The Cancer Genome Atlas Research Network, 2014⁵⁶	https://gdc.cancer.gov/
Synthetically generated dataset	This paper	Figshare: https://doi.org/10.6084/m9.figshare.20409430

Software and algorithms

EMu 1.5.2	Fischer et al., 2013²⁰	https://github.com/andrej-fischer/EMu
Maftools 2.2.0	Mayakonda et al., 2018²²	https://bioconductor.org/packages/release/bioc/html/maftools.html
MutationalPatterns 3.0.1	Blokzijl et al., 2018²⁴	https://bioconductor.org/packages/release/bioc/html/MutationalPatterns.html
MutSignatures 2.1.1	Fantini et al., 2020²⁵	https://CRAN.R-project.org/package=mutSignatures
MutSpec 2.0	Ardin et al., 2016²⁷	https://github.com/IARCbioinfo/mutspec
SigFit 2.0.0	Gori et al., 2020²⁸	https://github.com/kgori/sigfit
SigMiner 1.0.0	Wang et al., 2020³¹	https://github.com/ShixiangWang/sigminer
SignatureAnalyzer	Kasar et al., 2015³²; Taylor-Weiner et al., 2019³⁴	https://github.com/broadinstitute/SignatureAnalyzer-GPU
SignatureToolsLib 0.0.0.9000	Degasperi et al., 2020³⁵	https://github.com/Nik-Zainal-Group/signature.tools.lib
SigneR 1.16.0	Rosales et al., 2016³⁶	http://bioconductor.org/packages/release/bioc/html/signeR.html
SigProfiler_PCAWG (SigProExtractor) 0.0.5.48	Alexandrov et al., 2020¹²	https://pypi.org/project/sigproextractor/0.0.5.48/
SigProfilerExtractor 1.1.4	This paper	https://doi.org/10.5281/zenodo.6746540
SigProfilerExtractorR 1.1.0	This paper	https://doi.org/10.5281/zenodo.6941779
SigProfilerMatrixGenerator 1.2.4	Bergstrom et al., 2019¹⁵	https://github.com/AlexandrovLab/SigProfilerMatrixGenerator
SigProfilerSimulator 1.1.3	Bergstrom et al., 2020⁴⁸	https://github.com/AlexandrovLab/SigProfilerSimulator
SomaticSignatures 2.26.0	Gehring et al., 2015³⁸	https://bioconductor.org/packages/release/bioc/html/SomaticSignatures.html
SynSigGen	Alexandrov et al., 2020¹²	https://github.com/steverozen/SynSigGen
TensorSignatures 0.5.0	Vöhringer et al., 2021⁴⁰	https://github.com/sagar87/tensorsignatures

Other

Results from the benchmarking with synthetic datasets, including the appropriate input used to run each of the tools as well as the generated output	This paper	https://doi.org/10.6084/m9.figshare.20409430
Results from the benchmarking of the different options available in SigProfilerExtractor for matrix normalization, NMF initialization, and NMF objective function	This paper	https://doi.org/10.6084/m9.figshare.20411483
Results from the de novo extraction of mutational signatures from the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset	This paper	https://doi.org/10.6084/m9.figshare.20406279
Results from the de novo extraction of mutational signatures from the extended dataset	This paper	https://doi.org/10.6084/m9.figshare.20406326
Summarized collection of all input mutational matrices, as well as de novo extracted mutational signatures and activities for both PCAWG and extended datasets	This paper	https://doi.org/10.6084/m9.figshare.20293890
Results from the de novo extraction of mutational signatures for confirming the patterns of the novel signatures for additional datasets	This paper	https://doi.org/10.6084/m9.figshare.20406156
Results from the de novo extraction of mutational signatures from downsampling of whole-genome sequenced samples to whole-exomes	This paper	https://doi.org/10.6084/m9.figshare.20406276
Resource website for the COSMIC reference set of mutational signatures	Tate et al., 2019⁴²	https://cancer.sanger.ac.uk/signatures/