TY - JOUR

T1 - Towards routine chromosome-scale haplotype-resolved reconstruction in cancer genomics

AU - Garg, Shilpa

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-023-36689-5

DO - 10.1038/s41467-023-36689-5

M3 - Journal article

C2 - 36914638

AN - SCOPUS:85150104222

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1358

ER -