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Title: CNRein: an evolution-aware deep reinforcement learning algorithm for single-cell DNA copy number calling
Abstract Low-pass single-cell DNA sequencing technologies and algorithmic advancements have enabled haplotype-specific copy number calling on thousands of cells within tumors. However, measurement uncertainty may result in spurious CNAs inconsistent with realistic evolutionary constraints. We introduce evolution-aware copy number calling via deep reinforcement learning (CNRein). Our simulations demonstrate CNRein infers more accurate copy-number profiles and better recapitulates ground truth clonal structure than existing methods. On sequencing data of breast and ovarian cancer, CNRein produces more parsimonious solutions than existing methods while maintaining agreement with single-nucleotide variants. Additionally, CNRein shows consistency on a breast cancer patient sequenced with distinct low-pass technologies.  more » « less
Award ID(s):
2046488
PAR ID:
10581465
Author(s) / Creator(s):
;
Publisher / Repository:
Springer Science + Business Media
Date Published:
Journal Name:
Genome Biology
Volume:
26
Issue:
1
ISSN:
1474-760X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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