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Jointly Embedding Multiple Single-Cell Omics Measurements.

作者信息

Liu Jie, Huang Yuanhao, Singh Ritambhara, Vert Jean-Philippe, Noble William Stafford

机构信息

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.

Department of Genome Sciences, University of Washington, Seattle, WA, USA.

出版信息

Algorithms Bioinform. 2019 Sep 3;143. doi: 10.4230/LIPIcs.WABI.2019.10.


DOI:10.4230/LIPIcs.WABI.2019.10
PMID:34632462
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8496402/
Abstract

Many single-cell sequencing technologies are now available, but it is still difficult to apply multiple sequencing technologies to the same single cell. In this paper, we propose an unsupervised manifold alignment algorithm, MMD-MA, for integrating multiple measurements carried out on disjoint aliquots of a given population of cells. Effectively, MMD-MA performs an co-assay by embedding cells measured in different ways into a learned latent space. In the MMD-MA algorithm, single-cell data points from multiple domains are aligned by optimizing an objective function with three components: (1) a maximum mean discrepancy (MMD) term to encourage the differently measured points to have similar distributions in the latent space, (2) a distortion term to preserve the structure of the data between the input space and the latent space, and (3) a penalty term to avoid collapse to a trivial solution. Notably, MMD-MA does not require any correspondence information across data modalities, either between the cells or between the features. Furthermore, MMD-MA's weak distributional requirements for the domains to be aligned allow the algorithm to integrate heterogeneous types of single cell measures, such as gene expression, DNA accessibility, chromatin organization, methylation, and imaging data. We demonstrate the utility of MMD-MA in simulation experiments and using a real data set involving single-cell gene expression and methylation data.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb4/8496402/7e39bf958f11/nihms-1060040-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb4/8496402/6951df4a19e7/nihms-1060040-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb4/8496402/7e39bf958f11/nihms-1060040-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb4/8496402/6951df4a19e7/nihms-1060040-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb4/8496402/7e39bf958f11/nihms-1060040-f0002.jpg

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引用本文的文献

[1]
Cell-Type Annotation for scATAC-Seq Data by Integrating Chromatin Accessibility and Genome Sequence.

Biomolecules. 2025-6-27

[2]
Securing diagonal integration of multimodal single-cell data against ambiguous mapping.

Bioinformatics. 2025-6-2

[3]
SCOT+: A Comprehensive Software Suite for Single-Cell alignment Using Optimal Transport.

bioRxiv. 2025-5-27

[4]
Integration of single-cell transcriptome and chromatin accessibility and its application on tumor investigation.

Life Med. 2024-4-26

[5]
Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling.

Alzheimers Dement. 2025-1

[6]
scPair: Boosting single cell multimodal analysis by leveraging implicit feature selection and single cell atlases.

Nat Commun. 2024-11-15

[7]
A best-match approach for gene set analyses in embedding spaces.

Genome Res. 2024-10-11

[8]
Joint variational autoencoders for multimodal imputation and embedding.

Nat Mach Intell. 2023-6

[9]
Benchmarking computational methods for single-cell chromatin data analysis.

Genome Biol. 2024-8-16

[10]
A unified model for interpretable latent embedding of multi-sample, multi-condition single-cell data.

Nat Commun. 2024-8-3

本文引用的文献

[1]
Joint profiling of chromatin accessibility and gene expression in thousands of single cells.

Science. 2018-8-30

[2]
Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity.

Nat Methods. 2016-3

[3]
Single-cell chromatin accessibility reveals principles of regulatory variation.

Nature. 2015-7-23

[4]
Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity.

Nat Methods. 2014-7-20

[5]
Single-cell Hi-C reveals cell-to-cell variability in chromosome structure.

Nature. 2013-9-25

[6]
Unsupervised image matching based on manifold alignment.

IEEE Trans Pattern Anal Mach Intell. 2012-8

[7]
mRNA-Seq whole-transcriptome analysis of a single cell.

Nat Methods. 2009-5

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