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A unified model-based framework for doublet or multiplet detection in single-cell multiomics data.

Haoran Hu | Xinjun Wang | Site Feng | Zhongli Xu | Jing Liu | Elisa Heidrich-O'Hare | Yanshuo Chen | Molin Yue | Lang Zeng | Ziqi Rong | Tianmeng Chen | Timothy Billiar | Ying Ding | Heng Huang | Richard H Duerr | Wei Chen
Nature communications | 2024

Droplet-based single-cell sequencing techniques rely on the fundamental assumption that each droplet encapsulates a single cell, enabling individual cell omics profiling. However, the inevitable issue of multiplets, where two or more cells are encapsulated within a single droplet, can lead to spurious cell type annotations and obscure true biological findings. The issue of multiplets is exacerbated in single-cell multiomics settings, where integrating cross-modality information for clustering can inadvertently promote the aggregation of multiplet clusters and increase the risk of erroneous cell type annotations. Here, we propose a compound Poisson model-based framework for multiplet detection in single-cell multiomics data. Leveraging experimental cell hashing results as the ground truth for multiplet status, we conducted trimodal DOGMA-seq experiments and generated 17 benchmarking datasets from two tissues, involving a total of 280,123 droplets. We demonstrated that the proposed method is an essential tool for integrating cross-modality multiplet signals, effectively eliminating multiplet clusters in single-cell multiomics data-a task at which the benchmarked single-omics methods proved inadequate.

Pubmed ID: 38956023

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.),
    Id: U19AG055373
  • Agency: National Science Foundation (NSF),
    Id: NSF2225775
  • Agency: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.),
    Id: S10OD028483
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NIH HHS, United States
    Id: S10 OD028483
  • Agency: NIA NIH HHS, United States
    Id: U19 AG055373
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK138458
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM127027
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI106684
  • Agency: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.),
    Id: R35GM127027
  • Agency: NIDDK NIH HHS, United States
    Id: U01 DK062420
  • Agency: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.),
    Id: U01DK062420
  • Agency: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.),
    Id: R01DK138458
  • Agency: Leona M. and Harry B. Helmsley Charitable Trust (Helmsley Charitable Trust),
    Id: Helmsley Charitable Trust grant
  • Agency: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.),
    Id: P01AI106684

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