br d METHODS DETAILS br B Cell culture

d METHODS DETAILS
B Cell culture and isolation of single FLAG tag Peptide B DNA extraction and amplification
B Library preparation, sequencing and alignment B Genotyping of cell line samples
B Mutation discovery
B Mutational catalogs from stock cell lines and cell line clones
B Clonality of the cell line clones
B Mutational catalogs from single cells B Mutational catalogs from PDX models B Base substitution and indel classification B Kataegis quantification
B Sequence context quantification and enrichment analysis
B Doubling time measurements B Pathogen detection
B Identification of L1 mobile element insertions acquired in vitro 
B RNA sequencing and analysis
B 1,001 cell line panel expression and methylation datasets
d QUANTIFICATION AND STATISTICAL ANALYSIS B Mutational Signatures Analysis
B Relationships between somatic retrotransposition and APOBEC-associated SBS2 and SBS13
d DATA AND SOFTWARE AVAILABILITY
SUPPLEMENTAL INFORMATION
Supplemental Information can be found with this article online at https://doi.
ACKNOWLEDGMENTS
This work was supported by Wellcome grants 098051 and 206194; Cancer Research UK Grand Challenge Award C98/A24032 to L.B.A. and B.O.; the Li Ka Shing Foundation and National Institute for Health Research Oxford Biomedical Research Centre to D.C.W.; ED481A-2016/151 from Xunta de Ga-licia to B.R.–M. The use of pre-embargo PCAWG project mutational signatures data was approved by the PCAWG Steering Committee (excluding co-author P.J.C.) and the Mutational Signatures Working Group. Particular thanks to Jaegil Kim, Nicholas Haradhvala, Gaddy Getz, Steve Rozen, and other mem-bers of the PCAWG Working Group and to Graham Bignell for annotating mu-tation catalogs from 1,001 cell lines.
AUTHOR CONTRIBUTIONS
DECLARATION OF INTERESTS
During manuscript revision, M.P. was employed at Vertex Pharmaceuticals. U.M. is employed at AstraZeneca. Both were full-time employees of the Well-come Sanger Institute at the time of the primary manuscript draft preparation. M.R.S. is a member of the Grail Scientific Advisory Board.
REFERENCES
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Cesarman, E., Moore, P.S., Rao, P.H., Inghirami, G., Knowles, D.M., and Chang, Y. (1995). In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi’s sarcoma-associated herpesvirus-like (KSHV) DNA se-quences. Blood 86, 2708–2714.
Conticello, S.G. (2008). The AID/APOBEC family of nucleic acid mutators.
Freitas, T.A., Li, P.E., Scholz, M.B., and Chain, P.S. (2015). Accurate read-based metagenome characterization using a hierarchical suite of unique sig-natures. Nucleic Acids Res. 43, e69.
Petljak, M., and Alexandrov, L.B. (2016). Understanding mutagenesis through delineation of mutational signatures in human cancer. Carcinogenesis 37, 531–540.
Pfeifer, G.P. (2006). Mutagenesis at methylated CpG sequences. Curr. Top.
mutations in yeast and in human cancers can arise from damaged long sin-gle-strand DNA regions. Mol. Cell 46, 424–435.
Schneider-Ga¨dicke, A., and Schwarz, E. (1986). Different human cervical car-cinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO J. 5, 2285–2292.
STAR+METHODS
KEY RESOURCES TABLE
REAGENT or RESOURCE
SOURCE IDENTIFIER
Biological Samples
1,001 human cancer cell lines COSMIC Cell Line Project https://cancer.sanger.ac.uk/cell_lines
Critical Commercial Assays
Custom SureSelect Library Prep Kit
Agilent
SureSelect Targeted Enrichment kit
Agilent
illustra GenomiPhi V2 DNA amplification kit
GE Healthcare
Ribo-Zero rRNA Removal Kit
Illumina
KAPA Stranded mRNA-Seq Kit
Kapa Biosystems
ERCC RNA Spike-In Mix
Deposited Data
DNA sequence data
This paper
RNA sequence data
This paper
Software and Algorithms
Mapping workflow
Cancer, Aging and Somatic Mutation https://dockstore.org/containers/quay.io/
group, Wellcome Sanger Institute
wtsicgp/dockstore-cgpmap
Mutation calling workflows
Cancer, Aging and Somatic Mutation Whole-exome: https://dockstore.org/
group, Wellcome Sanger Institute containers/quay.io/wtsicgp/dockstore-cgpwxs
Whole-genome: https://dockstore.org/
containers/quay.io/wtsicgp/dockstore-cgpwgs
vafCorrect
Cancer, Aging and Somatic Mutation https://github.com/cancerit/vafCorrect