Evidence map›Paper›PMID 36999592›Full record

ArticleNucleic acids research2023

Single-cell individual full-length mtDNA sequencing by iMiGseq uncovers unexpected heteroplasmy shifts in mtDNA editing.

Chongwei Bi, Lin Wang, Yong Fan, Baolei Yuan, Gerardo Ramos-Mandujano, Yingzi Zhang, Samhan Alsolami, Xuan Zhou, Jincheng Wang, Yanjiao Shao and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Chongwei BiBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Lin WangBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Yong FanDepartment of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, 510150 Guangzhou, China.ORCID 0000-0002-7107-773X
Baolei YuanBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Gerardo Ramos-MandujanoBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Yingzi ZhangBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Samhan AlsolamiBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Xuan ZhouBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Jincheng WangBeijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, College of Chemistry, College of Engineering, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Yanjiao ShaoAltos Labs, San Diego, CA92121, USA.
Pradeep ReddyAltos Labs, San Diego, CA92121, USA.
Pu-Yao ZhangCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing100191, China.
Yanyi HuangBeijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, College of Chemistry, College of Engineering, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.ORCID 0000-0002-7297-1266
Yang YuCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing100191, China.
Juan Carlos Izpisua BelmonteBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.ORCID 0000-0003-0557-8875
Mo LiBioscience program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.ORCID 0000-0003-0827-8907
King Abdullah University of Science and Technology · SAPeking University · CNAltos LabsThird Affiliated Hospital of Guangzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ontogeny and dynamics of mtDNA heteroplasmy remain unclear due to limitations of current mtDNA sequencing methods. We developed individual Mitochondrial Genome sequencing (iMiGseq) of full-length mtDNA for ultra-sensitive variant detection, complete haplotyping, and unbiased evaluation of heteroplasmy levels, all at the individual mtDNA molecule level. iMiGseq uncovered unappreciated levels of heteroplasmic variants in single cells well below the conventional NGS detection limit and provided accurate quantitation of heteroplasmy level. iMiGseq resolved the complete haplotype of individual mtDNA in single oocytes and revealed genetic linkage of de novo mutations. iMiGseq detected sequential acquisition of detrimental mutations, including large deletions, in defective mtDNA in NARP/Leigh syndrome patient-derived induced pluripotent stem cells. iMiGseq identified unintended heteroplasmy shifts in mitoTALEN editing, while showing no appreciable level of unintended mutations in DdCBE-mediated mtDNA base editing. Therefore, iMiGseq could not only help elucidate the mitochondrial etiology of diseases, but also evaluate the safety of various mtDNA editing strategies.

Indexed as

DNA, MitochondrialGenome, MitochondrialHeteroplasmyMitochondriaMutationDNA, Mitochondrial

Identifiers

PMID36999592
PMCPMC10164560
OpenAlexW4362457900

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.