MetaQ: fast, scalable and accurate metacell inference via single-cell quantization

Abstract To overcome the computational barriers of analyzing large-scale single-cell sequencing data, we introduce MetaQ, a metacell algorithm that scales to arbitrarily large datasets with linear runtime and constant memory usage. Inspired by cellular development, MetaQ conceptualizes each metacell...

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Main Authors: Yunfan Li, Hancong Li, Yijie Lin, Dan Zhang, Dezhong Peng, Xiting Liu, Jie Xie, Peng Hu, Lu Chen, Han Luo, Xi Peng
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56424-6
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author Yunfan Li
Hancong Li
Yijie Lin
Dan Zhang
Dezhong Peng
Xiting Liu
Jie Xie
Peng Hu
Lu Chen
Han Luo
Xi Peng
author_facet Yunfan Li
Hancong Li
Yijie Lin
Dan Zhang
Dezhong Peng
Xiting Liu
Jie Xie
Peng Hu
Lu Chen
Han Luo
Xi Peng
author_sort Yunfan Li
collection DOAJ
description Abstract To overcome the computational barriers of analyzing large-scale single-cell sequencing data, we introduce MetaQ, a metacell algorithm that scales to arbitrarily large datasets with linear runtime and constant memory usage. Inspired by cellular development, MetaQ conceptualizes each metacell as a collective ancestor of biologically similar cells. By quantizing cells into a discrete codebook, where each entry represents a metacell capable of reconstructing the original cells it quantizes, MetaQ identifies homogeneous cell subsets for efficient and accurate metacell inference. This approach reduces computational complexity from exponential to linear while maintaining or surpassing the performance of existing metacell algorithms. Extensive experiments demonstrate that MetaQ excels in downstream tasks such as cell type annotation, developmental trajectory inference, batch integration, and differential expression analysis. Thanks to its superior efficiency and effectiveness, MetaQ makes analyzing datasets with millions of cells practical, offering a powerful solution for single-cell studies in the era of high-throughput profiling.
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issn 2041-1723
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publishDate 2025-01-01
publisher Nature Portfolio
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series Nature Communications
spelling doaj-art-0688f7368c9b4f56abcbaba6e28828482025-02-02T12:32:43ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-025-56424-6MetaQ: fast, scalable and accurate metacell inference via single-cell quantizationYunfan Li0Hancong Li1Yijie Lin2Dan Zhang3Dezhong Peng4Xiting Liu5Jie Xie6Peng Hu7Lu Chen8Han Luo9Xi Peng10School of Computer Science, Sichuan UniversityDepartment of Thyroid and Parathyroid Surgery, Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease Related Molecular Network, West China Hospital, Sichuan UniversitySchool of Computer Science, Sichuan UniversityDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan UniversitySchool of Computer Science, Sichuan UniversitySchool of Computer Science, Georgia Insitute of TechnologyCollege of Life Science, Sichuan Normal UniversitySchool of Computer Science, Sichuan UniversityDepartment of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan UniversityDepartment of Thyroid and Parathyroid Surgery, Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease Related Molecular Network, West China Hospital, Sichuan UniversitySchool of Computer Science, Sichuan UniversityAbstract To overcome the computational barriers of analyzing large-scale single-cell sequencing data, we introduce MetaQ, a metacell algorithm that scales to arbitrarily large datasets with linear runtime and constant memory usage. Inspired by cellular development, MetaQ conceptualizes each metacell as a collective ancestor of biologically similar cells. By quantizing cells into a discrete codebook, where each entry represents a metacell capable of reconstructing the original cells it quantizes, MetaQ identifies homogeneous cell subsets for efficient and accurate metacell inference. This approach reduces computational complexity from exponential to linear while maintaining or surpassing the performance of existing metacell algorithms. Extensive experiments demonstrate that MetaQ excels in downstream tasks such as cell type annotation, developmental trajectory inference, batch integration, and differential expression analysis. Thanks to its superior efficiency and effectiveness, MetaQ makes analyzing datasets with millions of cells practical, offering a powerful solution for single-cell studies in the era of high-throughput profiling.https://doi.org/10.1038/s41467-025-56424-6
spellingShingle Yunfan Li
Hancong Li
Yijie Lin
Dan Zhang
Dezhong Peng
Xiting Liu
Jie Xie
Peng Hu
Lu Chen
Han Luo
Xi Peng
MetaQ: fast, scalable and accurate metacell inference via single-cell quantization
Nature Communications
title MetaQ: fast, scalable and accurate metacell inference via single-cell quantization
title_full MetaQ: fast, scalable and accurate metacell inference via single-cell quantization
title_fullStr MetaQ: fast, scalable and accurate metacell inference via single-cell quantization
title_full_unstemmed MetaQ: fast, scalable and accurate metacell inference via single-cell quantization
title_short MetaQ: fast, scalable and accurate metacell inference via single-cell quantization
title_sort metaq fast scalable and accurate metacell inference via single cell quantization
url https://doi.org/10.1038/s41467-025-56424-6
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