dc.contributor.author | Guo, Q | |
dc.contributor.author | Lakatos, E | |
dc.contributor.author | Bakir, IA | |
dc.contributor.author | Curtius, K | |
dc.contributor.author | Graham, TA | |
dc.contributor.author | Mustonen, V | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-12-14T09:27:44Z | |
dc.date.available | 2022-12-14T09:27:44Z | |
dc.date.issued | 2022-09-06 | |
dc.identifier | ARTN 4487 | |
dc.identifier | 10.1038/s41467-022-32041-5 | |
dc.identifier.citation | Nature Communications, 2022, 13 (1), pp. 4487 - | en_US |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5607 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-022-32041-5 | |
dc.description.abstract | Clinical archives of patient material near-exclusively consist of formalin-fixed and paraffin-embedded (FFPE) blocks. The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous translational potential. However, sequencing of DNA derived from FFPE material is known to be riddled with artefacts. Here we derive genome-wide mutational signatures caused by formalin fixation. We show that the FFPE-signature is highly similar to signature 30 (the signature of Base Excision Repair deficiency due to NTHL1 mutations), and chemical repair of DNA lesions leads to a signature highly similar to signature 1 (clock-like signature due to spontaneous deamination of methylcytosine). We demonstrate that using uncorrected mutational catalogues of FFPE samples leads to major mis-assignment of signature activities. To correct for this, we introduce FFPEsig, a computational algorithm to rectify the formalin-induced artefacts in the mutational catalogue. We demonstrate that FFPEsig enables accurate mutational signature analysis both in simulated and whole-genome sequenced FFPE cancer samples. FFPEsig thus provides an opportunity to unlock additional clinical potential of archival patient tissues. | |
dc.format | Electronic | |
dc.format.extent | 4487 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | NATURE PORTFOLIO | en_US |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Formaldehyde | |
dc.subject | Genome, Human | |
dc.subject | Humans | |
dc.subject | Mutation | |
dc.subject | Paraffin Embedding | |
dc.subject | Tissue Fixation | |
dc.title | The mutational signatures of formalin fixation on the human genome. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-07-14 | |
dc.date.updated | 2022-12-14T09:26:59Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1038/s41467-022-32041-5 | en_US |
rioxxterms.licenseref.startdate | 2022-09-06 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36068219 | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Genomics and evolutionary dynamics | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41467-022-32041-5 | |
pubs.volume | 13 | |
icr.researchteam | Genomics & evolut dynam | en_US |
dc.contributor.icrauthor | Graham, Trevor | |
icr.provenance | Deposited by Mr Arek Surman on 2022-12-14. Deposit type is initial. No. of files: 1. Files: The mutational signatures of formalin fixation on the human genome.pdf | |