Evidence map›Paper›PMID 36511385›Full record

ArticleBiostatistics (Oxford, England)2023

Inference after latent variable estimation for single-cell RNA sequencing data.

Anna Neufeld, Lucy L Gao, Joshua Popp, Alexis Battle, Daniela Witten

Abstract read
In one paragraph

Article in Biostatistics (Oxford, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–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

44 citing papers in PubMed.

  1. Article
  2. Article
  3. Multimodal analysis reveals cellular diversity and divergent circuits of the zona incerta.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Classification with Missing Data - AbioRxiv : the preprint server for biology · 2026
    Article
  8. Article
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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

5 authors.

Anna NeufeldDepartment of Statistics, University of Washington, Seattle, WA 98195, USA.
Lucy L GaoDepartment of Statistics, University of British Columbia, BC V6T 1Z4, Canada.
Joshua PoppDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Alexis BattleDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA and Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA.
Daniela WittenDepartment of Statistics, University of Washington, Seattle, WA 98195, USA and Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.

Funding

Modeling the dynamicimpact of rare and common genetic variation on gene expression anddiseaseR35GM139580 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BATTLE, ALEXIS · 2021 to 2025
$3.1M
A Modeling Framework for Multi-View Data, with Applications to the Pioneer 100 Study and Protein Interaction NetworksR01GM123993 · NIGMS · UNIVERSITY OF WASHINGTON · PI BIEN, JACOB, WITTEN, DANIELA · 2017 to 2020
$1.3M
Models and Methods for Calcium Imaging Data with Application to the Allen Brain ObservatoryR01EB026908 · NIBIB · UNIVERSITY OF WASHINGTON · PI BUICE, MICHAEL, WITTEN, DANIELA · 2018 to 2020
$1.1M
CRCNS: Theory and Experiments to Elucidate Neural Coding in the Reward CircuitR01DA047869 · NIDA · UNIVERSITY OF WASHINGTON · PI WITTEN, DANIELA, WITTEN, ILANA · 2018 to 2021
$1.0M
NIBIB NIH HHS R01 EB026908NIDA NIH HHS R01 DA047869NIGMS NIH HHS R01 GM123993NIGMS NIH HHS R35 GM139580
6 · The paper itself

Abstract

In the analysis of single-cell RNA sequencing data, researchers often characterize the variation between cells by estimating a latent variable, such as cell type or pseudotime, representing some aspect of the cell's state. They then test each gene for association with the estimated latent variable. If the same data are used for both of these steps, then standard methods for computing p-values in the second step will fail to achieve statistical guarantees such as Type 1 error control. Furthermore, approaches such as sample splitting that can be applied to solve similar problems in other settings are not applicable in this context. In this article, we introduce count splitting, a flexible framework that allows us to carry out valid inference in this setting, for virtually any latent variable estimation technique and inference approach, under a Poisson assumption. We demonstrate the Type 1 error control and power of count splitting in a simulation study and apply count splitting to a data set of pluripotent stem cells differentiating to cardiomyocytes.

Indexed as

Computer SimulationHumansSequence Analysis, RNABinomial thinningClusteringPoissonPseudotimeSample splittingSelective inference

Identifiers

PMID36511385
PMCPMC12235260

What OpenQuestion holds

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Registered trials

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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.