Evidence map›Paper›PMID 31282856›Full record

ArticleeLife2019

Identifying gene expression programs of cell-type identity and cellular activity with single-cell RNA-Seq.

Dylan Kotliar, Adrian Veres, M Aurel Nagy, Shervin Tabrizi, Eran Hodis, Douglas A Melton, Pardis C Sabeti

Abstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 366 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
366citing 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

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

  1. Pooled it
  2. Trial
  3. 4-1BBCell reports. Medicine · 2025
    Trial
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  8. Review
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  11. A Gene-Program Architecture of Mouse T cells.bioRxiv : the preprint server for biology · 2026
    Article
  12. Article
  13. Article
  14. Brain Architecture of Punishment Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  15. Article
  16. Article
  17. Article
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  19. Article
  20. scENature communications · 2026
    Article

306 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Dylan Kotliar *Department of Systems Biology, Harvard Medical School, Boston, United States.ORCID 0000-0002-7968-645X
Adrian Veres *Department of Systems Biology, Harvard Medical School, Boston, United States.
M Aurel NagyHarvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, United States.ORCID 0000-0003-4608-1152
Shervin TabriziBroad Institute of MIT and Harvard, Cambridge, United States.ORCID 0000-0003-2780-8432
Eran HodisHarvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, United States.
Douglas A MeltonHarvard Stem Cell Institute, Harvard University, Cambridge, United States.ORCID 0000-0002-1623-5504
Pardis C SabetiDepartment of Systems Biology, Harvard Medical School, Boston, United States.

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Elucidating Genetic Determinants of Resistance to Lassa Hemorrhagic FeverR01AI114855 · NIAID · BROAD INSTITUTE, INC. · PI SABETI, PARDIS CHRISTINE · 2015 to 2019
$3.8M
Design of a human monoclonal antibody-informed dengue vaccineR01AI099210 · NIAID · FLORIDA GULF COAST UNIVERSITY · PI ISERN, SHARON · 2013 to 2016
$1.7M
NIAID NIH HHS R01 AI099210NIAID NIH HHS R01 AI114855NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32GM007753
6 · The paper itself

Abstract

Identifying gene expression programs underlying both cell-type identity and cellular activities (e.g. life-cycle processes, responses to environmental cues) is crucial for understanding the organization of cells and tissues. Although single-cell RNA-Seq (scRNA-Seq) can quantify transcripts in individual cells, each cell's expression profile may be a mixture of both types of programs, making them difficult to disentangle. Here, we benchmark and enhance the use of matrix factorization to solve this problem. We show with simulations that a method we call consensus non-negative matrix factorization (cNMF) accurately infers identity and activity programs, including their relative contributions in each cell. To illustrate the insights this approach enables, we apply it to published brain organoid and visual cortex scRNA-Seq datasets; cNMF refines cell types and identifies both expected (e.g. cell cycle and hypoxia) and novel activity programs, including programs that may underlie a neurosecretory phenotype and synaptogenesis.

Indexed as

AlgorithmsAnimalsBrainComputer SimulationGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansMiceModels, GeneticOrganoidsReproducibility of ResultsRNA-SeqSingle-Cell AnalysisVisual Cortexbrain organoidscomputational biologygene expression programsgeneticsgenomicshumanmatrix factorizationmousesingle-cell Rna-Seqsynaptogenesissystems biologyvisual cortex

Identifiers

PMID31282856
PMCPMC6639075

What OpenQuestion holds

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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.