Resolving the Haplotype Complexity of Colorectal Cancer Genomes with Droplet Barcode Sequencing.
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Siga H, Höjer P, Pourbozorgi P, Aghelpasand H, Käller M, Hartman J, Williams C, Ahmadian A
Life (Basel) 16 (6) - [2026-05-22; online 2026-05-22]
Precision medicine is increasingly applied in the cancer clinic, adapting treatment to genomic alterations of the tumor. However, whether alterations disrupt the function of a protein can depend on if both alleles of a gene are altered. While massively parallel sequencing technologies can identify sequence aberrations, they are limited in resolving the corresponding haplotype information. In this proof-of-concept case study, we applied the linked-read droplet barcode sequencing (DBS) technology to resolve the haplotype complexity of colorectal cancer genomes on paired tumor and normal samples. Several cancer-related genes carried multiple mutations in either one or both haplotypes. Additionally, a number of haplotype-resolved large structural variants and copy number alterations were detected and phased with short somatic variants. Nearly all characterized oncogenic pathways harbored some of the identified short somatic variants. The study demonstrates that linked-read DBS technology can characterize complex genetic variations in a haplotype context and may provide essential information for personalized approaches.
NGI Stockholm (Genomics Applications) [Collaborative]
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 42355402
DOI 10.3390/life16060874
Crossref 10.3390/life16060874
pii: life16060874
pmc: PMC13301505