Refphase: Multi-sample reference phasing reveals haplotype-specific copy number heterogeneity

Watkins, T. B.; Colliver, E. C.; Huska, M. R.; Kaufmann, T. L.; Lim, E. L.; Haase, K.; Van Loo, P.; Swanton, C.; McGranahan, N.; Schwarz, R. F.

doi:10.1101/2022.10.13.511885

bioRxiv · 10.1101/2022.10.13.511885

Refphase: Multi-sample reference phasing reveals haplotype-specific copy number heterogeneity

Watkins, T. B.·Colliver, E. C.·Huska, M. R.·Kaufmann, T. L.·Lim, E. L.·Haase, K.·Van Loo, P.·Swanton, C.·McGranahan, N.·Schwarz, R. F.

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Abstract

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patients disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample reference phasing. We demonstrate Refphases ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours.

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Watkins, T. B., Colliver, E. C., Huska, M. R., Kaufmann, T. L., Lim, E. L., Haase, K., Van Loo, P., Swanton, C., McGranahan, N., Schwarz, R. F.. 2022-10-17. Refphase: Multi-sample reference phasing reveals haplotype-specific copy number heterogeneity. https://doi.org/10.1101/2022.10.13.511885

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