{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:40:48Z","timestamp":1770990048902,"version":"3.50.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["U24CA248453"],"award-info":[{"award-number":["U24CA248453"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["U24CA264027"],"award-info":[{"award-number":["U24CA264027"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Eukaryotic cells contain organelles called mitochondria that have their own genome. Most cells contain thousands of mitochondria which replicate, even in nondividing cells, by means of a relatively error-prone process resulting in somatic mutations in their genome. Because of the higher mutation rate compared to the nuclear genome, mitochondrial mutations have been used to track cellular lineage, particularly using single-cell sequencing that measures mitochondrial mutations in individual cells. However, existing methods to infer the cell lineage tree from mitochondrial mutations do not model \u201cheteroplasmy,\u201d which is the presence of multiple mitochondrial clones with distinct sets of mutations in an individual cell. Single-cell sequencing data thus provide a mixture of the mitochondrial clones in individual cells, with the ancestral relationships between these clones described by a mitochondrial clone tree. While deconvolution of somatic mutations from a mixture of evolutionarily related genomes has been extensively studied in the context of bulk sequencing of cancer tumor samples, the problem of mitochondrial deconvolution has the additional constraint that the mitochondrial clone tree must be concordant with the cell lineage tree.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We formalize the problem of inferring a concordant pair of a mitochondrial clone tree and a cell lineage tree from single-cell sequencing data as the Nested Perfect Phylogeny Mixture (NPPM) problem. We derive a combinatorial characterization of the solutions to the NPPM problem, and formulate an algorithm, MERLIN, to solve this problem exactly using a mixed integer linear program. We show on simulated data that MERLIN outperforms existing methods that do not model mitochondrial heteroplasmy nor the concordance between the mitochondrial clone tree and the cell lineage tree. We use MERLIN to analyze single-cell whole-genome sequencing data of 5220 cells of a gastric cancer cell line and show that MERLIN infers a more biologically plausible cell lineage tree and mitochondrial clone tree compared to existing methods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>https:\/\/github.com\/raphael-group\/MERLIN.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae231","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T09:26:37Z","timestamp":1719566797000},"page":"i218-i227","source":"Crossref","is-referenced-by-count":3,"title":["Joint inference of cell lineage and mitochondrial evolution from single-cell sequencing data"],"prefix":"10.1093","volume":"40","author":[{"given":"Palash","family":"Sashittal","sequence":"first","affiliation":[{"name":"Department of Computer Science, Princeton University , Princeton, NJ 08540, United States"}]},{"given":"Viola","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Princeton University , Princeton, NJ 08540, United States"}]},{"given":"Amey","family":"Pasarkar","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Princeton University , Princeton, NJ 08540, United States"}]},{"given":"Benjamin J","family":"Raphael","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Princeton University , Princeton, NJ 08540, United States"}]}],"member":"286","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"2024062809024639700_btae231-B1","doi-asserted-by":"crossref","first-page":"i408","DOI":"10.1093\/bioinformatics\/btz312","article-title":"Summarizing the solution space in tumor phylogeny inference by multiple consensus 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