Evidence map›Paper›PMID 33875866›Full record

ArticleNature biotechnology2021

Iterative single-cell multi-omic integration using online learning.

Chao Gao, Jialin Liu, April R Kriebel, Sebastian Preissl, Chongyuan Luo, Rosa Castanon, Justin Sandoval, Angeline Rivkin, Joseph R Nery, Margarita M Behrens and 3 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

68 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. LIGER2: Scalable Single-Cell Integration with On-Disk Datasets.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Unifying multimodal single-cell data with a mixture-of-expertsbioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
  9. Orthogonal disentanglement of single-cell multi-omics reveals private and shared drivers of tissue development and pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  11. Review
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8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Chao GaoDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9316-2185
Jialin LiuDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
April R KriebelDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Sebastian PreisslCenter for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-8971-5616
Chongyuan LuoGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Rosa CastanonGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Justin SandovalGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Angeline RivkinGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Joseph R NeryGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0153-5659
Margarita M BehrensComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Joseph R EckerGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5799-5895
Bing RenCenter for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Joshua D WelchDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. welchjd@umich.edu.ORCID http://orcid.org/0000-0002-5869-2391

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
Molecular SignaturesU19MH114831 · NIMH · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI CALLAWAY, EDWARD M, ECKER, JOSEPH R · 2017 to 2021
$24.6M
University of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4M
Quantitative definition of cell identity from single-cell multi-omic, spatial, and perturbation dataR01HG010883 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joshua Welch · 2019 to 2026
$4.4M
Integrative Single-Cell Analysis of Transcriptome, Epigenome, and Lineage in HIV Latency and ActivationR01AI149669 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L., WELCH, JOSHUA · 2020 to 2024
$3.4M
Linking molecular and anatomical features of brain cell identity through computational data integrationRF1MH123199 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WELCH, JOSHUA · 2020 to 2020
$1.1M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014195NHGRI NIH HHS R01 HG010883NHGRI NIH HHS T32 HG000040NIAID NIH HHS R01 AI149669NIMH NIH HHS RF1 MH123199NIMH NIH HHS U19 MH114831
6 · The paper itself

Abstract

Integrating large single-cell gene expression, chromatin accessibility and DNA methylation datasets requires general and scalable computational approaches. Here we describe online integrative non-negative matrix factorization (iNMF), an algorithm for integrating large, diverse and continually arriving single-cell datasets. Our approach scales to arbitrarily large numbers of cells using fixed memory, iteratively incorporates new datasets as they are generated and allows many users to simultaneously analyze a single copy of a large dataset by streaming it over the internet. Iterative data addition can also be used to map new data to a reference dataset. Comparisons with previous methods indicate that the improvements in efficiency do not sacrifice dataset alignment and cluster preservation performance. We demonstrate the effectiveness of online iNMF by integrating more than 1 million cells on a standard laptop, integrating large single-cell RNA sequencing and spatial transcriptomic datasets, and iteratively constructing a single-cell multi-omic atlas of the mouse motor cortex.

Indexed as

AlgorithmsMachine LearningAnimalsComputational BiologyMiceMultivariate AnalysisSingle-Cell AnalysisTranscriptome

Identifiers

PMID33875866
PMCPMC8355612

What OpenQuestion holds

Textmetadata
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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.