Towards routine chromosome-scale haplotype-resolved reconstruction in cancer genomics

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  • Shilpa Garg
Cancer genomes are highly complex and heterogeneous. The standard short-read sequencing and analytical methods are unable to provide the complete and precise base-level structural variant landscape of cancer genomes. In this work, we apply high-resolution long accurate HiFi and long-range Hi-C sequencing to the melanoma COLO829 cancer line. Also, we develop an efficient graph-based approach that processes these data types for chromosome-scale haplotype-resolved reconstruction to characterise the cancer precise structural variant landscape. Our method produces high-quality phased scaffolds on the chromosome level on three healthy samples and the COLO829 cancer line in less than half a day even in the absence of trio information, outperforming existing state-of-the-art methods. In the COLO829 cancer cell line, here we show that our method identifies and characterises precise somatic structural variant calls in important repeat elements that were missed in short-read-based call sets. Our method also finds the precise chromosome-level structural variant (germline and somatic) landscape with 19,956 insertions, 14,846 deletions, 421 duplications, 52 inversions and 498 translocations at the base resolution. Our simple pstools approach should facilitate better personalised diagnosis and disease management, including predicting therapeutic responses.
OriginalsprogEngelsk
Artikelnummer1358
TidsskriftNature Communications
Vol/bind14
Udgave nummer1
Antal sider11
ISSN2041-1723
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The author is thankful to George Church from Harvard Medical School, Anthony Schmitt from Arima Genomics and Nancy Francoeur for Mt. Sinai for providing necessary support on sequencing technologies. Thanks are also due to the Human Pangenome Reference consortium (HPRC) for HiFi and Hi-C datasets. Lastly, the author acknowledges the productive comments from anonymous reviewers and the support from the Novo Nordisk Foundation (NNF21OC0069089).

Funding Information:
The author is thankful to George Church from Harvard Medical School, Anthony Schmitt from Arima Genomics and Nancy Francoeur for Mt. Sinai for providing necessary support on sequencing technologies. Thanks are also due to the Human Pangenome Reference consortium (HPRC) for HiFi and Hi-C datasets. Lastly, the author acknowledges the productive comments from anonymous reviewers and the support from the Novo Nordisk Foundation (NNF21OC0069089).

Publisher Copyright:
© 2023, The Author(s).

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