정영수 (연세대학교)

한빛사논문

조회293

정영수Young-soo Chung

연세대학교

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Nucleic Acids Res., Jun 26 2024, gkae527 | https://doi.org/10.1093/nar/gkae527 CLEMENT: genomic decomposition and reconstruction of non-tumor subclones

Young-soo Chung ^1,†, Seungseok Kang ^1,†, Jisu Kim ^2,3, Sangbo Lee ¹ and Sangwoo Kim^1,*

¹Department of Biomedical Systems Informatics, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

²DataShape team, Inria Saclay Île-De-France, Palaiseau 91120, France

³Department of Statistics, Seoul National University, Seoul 08826, Republic of Korea

*To whom correspondence should be addressed. : Sangwoo Kim

^†The first two authors should be regarded as Joint First Authors.

Abstract

Genome-level clonal decomposition of a single specimen has been widely studied; however, it is mostly limited to cancer research. In this study, we developed a new algorithm CLEMENT, which conducts accurate decomposition and reconstruction of multiple subclones in genome sequencing of non-tumor (normal) samples. CLEMENT employs the Expectation-Maximization (EM) algorithm with optimization strategies specific to non-tumor subclones, including false variant call identification, non-disparate clone fuzzy clustering, and clonal allele fraction confinement. In the simulation and in vitro cell line mixture data, CLEMENT outperformed current cancer decomposition algorithms in estimating the number of clones (root-mean-square-error = 0.58-0.78 versus 1.43-3.34) and in the variant-clone membership agreement (∼85.5% versus 70.1-76.7%). Additional testing on human multi-clonal normal tissue sequencing confirmed the accurate identification of subclones that originated from different cell types. Clone-level analysis, including mutational burden and signatures, provided a new understanding of normal-tissue composition. We expect that CLEMENT will serve as a crucial tool in the currently emerging field of non-tumor genome analysis.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-27)
연구진국내 연구진
분야 의약학 > 유전 및 유전체의학

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