Evidence map›Paper›PMID 32661426›Full record

ArticleNature methods2020

Investigating higher-order interactions in single-cell data with scHOT.

Shila Ghazanfar, Yingxin Lin, Xianbin Su, David Ming Lin, Ellis Patrick, Ze-Guang Han, John C Marioni, Jean Yee Hwa Yang

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

  1. Pooled it
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  7. Spatial omics for profiling the dynamic tumor microenvironment.Clinical & translational immunology · 2026
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  10. Cancer therapy resistance from a spatial-omics perspective.Clinical and translational medicine · 2025
    Review
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  14. Spatial Transcriptomics in Human Cardiac Tissue.International journal of molecular sciences · 2025
    Review
  15. Article
  16. Article
  17. Article
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  19. Article
  20. Review
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

8 authors at 5 institutions in 5 countries.

Shila GhazanfarCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Yingxin LinSchool of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia.
Xianbin SuKey Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.ORCID http://orcid.org/0000-0001-5705-6062
David Ming LinDepartment of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
Ellis PatrickSchool of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-5253-4747
Ze-Guang HanKey Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
John C Marioni *Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. marioni@ebi.ac.uk.ORCID http://orcid.org/0000-0001-9092-0852
Jean Yee Hwa Yang *School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia. jean.yang@sydney.edu.au.ORCID http://orcid.org/0000-0002-5271-2603
The University of Sydney · AUShanghai Jiao Tong University · CNCornell University · USEuropean Bioinformatics Institute · GBUniversity of Cambridge · GB

Funding

Protocadherins in vertebrate self recognitionR21DC015107 · NIDCD · CORNELL UNIVERSITY · PI LIN, DAVID M. · 2017 to 2018
$412k
Cancer Research UK 17197Cancer Research UK 22231Cancer Research UK A22231NIDCD NIH HHS R21 DC015107
6 · The paper itself

Abstract

Single-cell genomics has transformed our ability to examine cell fate choice. Examining cells along a computationally ordered 'pseudotime' offers the potential to unpick subtle changes in variability and covariation among key genes. We describe an approach, scHOT-single-cell higher-order testing-which provides a flexible and statistically robust framework for identifying changes in higher-order interactions among genes. scHOT can be applied for cells along a continuous trajectory or across space and accommodates various higher-order measurements including variability or correlation. We demonstrate the use of scHOT by studying coordinated changes in higher-order interactions during embryonic development of the mouse liver. Additionally, scHOT identifies subtle changes in gene-gene correlations across space using spatially resolved transcriptomics data from the mouse olfactory bulb. scHOT meaningfully adds to first-order differential expression testing and provides a framework for interrogating higher-order interactions using single-cell data.

Indexed as

AnimalsComputational BiologyDatabases, Nucleic AcidHepatocytesLiverMiceOligonucleotide Array Sequence AnalysisSequence Analysis, RNASingle-Cell AnalysisSoftware

Identifiers

PMID32661426
PMCPMC7610653
OpenAlexW3041345852

What OpenQuestion holds

Textmetadata
LicenceTDM
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.