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Updated: Oct 1, 2025

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

MQuad enables clonal substructure discovery using single cell mitochondrial variants.

Aaron Wing Cheung Kwok¹, Chen Qiao¹, Rongting Huang¹

¹School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Nature Communications

|March 9, 2022

Summary

This summary is machine-generated.

Mitochondrial DNA (mtDNA) variants can reveal cell lineages, but are hard to detect in single-cell data. We developed MQuad, an open-source tool that accurately identifies these variants, improving clonal structure analysis.

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An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

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Published on: March 9, 2022

Area of Science:

Genomics
Computational Biology
Cell Biology

Background:

Mitochondrial DNA (mtDNA) mutations are valuable endogenous markers for reconstructing cellular clonal structures.
Analyzing mtDNA variants in sparse and noisy single-cell sequencing data presents significant computational challenges.
Existing computational methods for identifying informative mtDNA variants are limited.

Purpose of the Study:

To introduce MQuad, an open-source computational tool for accurate identification of clonally informative mtDNA variants.
To provide an analysis suite for comprehensive clonality inference using various single-cell sequencing data types.
To enhance the resolution of clonal structures by leveraging mtDNA variants.

Main Methods:

Development of the MQuad computational tool for variant calling.
Application of MQuad to simulated and experimental single-cell RNA, DNA, and ATAC sequencing data.
Comparative analysis against existing methods for variant identification accuracy.

Main Results:

MQuad accurately identifies clonally informative mtDNA variants with high sensitivity and specificity.
MQuad significantly outperforms existing methods in variant calling accuracy.
The tool demonstrates broad applicability across different single-cell sequencing protocols.

Conclusions:

MQuad provides a robust solution for identifying mtDNA variants in single-cell data.
The tool enhances the ability to infer cellular clonal structures with greater precision.
MQuad complements existing variation analyses (e.g., SNVs, CNVs) for finer clonal resolution.