Accurate calling of low-frequency somatic mutations by sample-specific modeling of error rates DOI Creative Commons

Yixin Lin,

Carmen Oroperv,

Peter Sørud Porsgård

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract Calling rare somatic variants from NGS data is more challenging than calling inherited variants, especially if the variant only present in a small fraction of cells sequenced biopsy. In this case, having good estimate error rate specific base particular read becomes essential. paired-end sequencing, where some DNA fragments are shorter twice length, overlapping regions pairs an ideal resource for training models to discern context-dependent rates, as any discordant bases overlaps must be caused by sequencing or alignment error. We have created new tool named BBQ (an acronym Better Base Quality) that uses reads conditional on mutation type, sequence context, and quality. also how much concordant decreased compared non-overlapping reads. Results show can remove errors induced damage increased quality differs between samples types, reflecting different patterns samples. use call variants. Sequencing testis biopsy cell-free sample serve proof-of-concept germ cell detecting cancer mutations. find using sample-specific allows us with fewer false positives existing tools such Mutect2 Strelka2.

Language: Английский

Minimal residual disease in colorectal cancer. Tumor-informed versus tumor-agnostic approaches: unraveling the optimal strategy DOI
B. Martínez-Castedo, Daniel G. Camblor,

J. Martín-Arana

et al.

Annals of Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

5
Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas DOI Creative Commons
Amanda Frydendahl, Adam J. Widman,

Nadia Øgaard

et al.

Molecular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

The presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor‐agnostic approaches report ctDNA 10–15% patients, though uncertainty as to whether the signal originates from adenoma. To obtain an accurate estimate proportion ctDNA, a sensitive tumor‐informed strategy is preferred, it ensures detected Here, whole‐genome sequencing‐based analysis (MRD‐EDGE SNV ) was applied two independent cohorts. Cohort 1, comprising 93 stage III cancer (CRC) and 40 healthy individuals, used establish threshold at 95% specificity. This then 2, consisting 22 symptomatic 20 asymptomatic adenomas. In III, MRD‐EDGE had area under curve 0.98. 50% 25% adenomas, respectively. median adenoma plasma fraction 5.9 × 10 −5 . These finding not only demonstrate feasibility detection but also provides necessary sensitivity required detect these lesions, paving way for future ctDNA‐based screening strategies.

Language: Английский

Citations

0
Accurate calling of low-frequency somatic mutations by sample-specific modeling of error rates DOI Creative Commons

Yixin Lin,

Carmen Oroperv,

Peter Sørud Porsgård

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract Calling rare somatic variants from NGS data is more challenging than calling inherited variants, especially if the variant only present in a small fraction of cells sequenced biopsy. In this case, having good estimate error rate specific base particular read becomes essential. paired-end sequencing, where some DNA fragments are shorter twice length, overlapping regions pairs an ideal resource for training models to discern context-dependent rates, as any discordant bases overlaps must be caused by sequencing or alignment error. We have created new tool named BBQ (an acronym Better Base Quality) that uses reads conditional on mutation type, sequence context, and quality. also how much concordant decreased compared non-overlapping reads. Results show can remove errors induced damage increased quality differs between samples types, reflecting different patterns samples. use call variants. Sequencing testis biopsy cell-free sample serve proof-of-concept germ cell detecting cancer mutations. find using sample-specific allows us with fewer false positives existing tools such Mutect2 Strelka2.

Language: Английский

Citations

0