Evidence map›Paper›PMID 40195561›Full record

ArticleNature genetics2025

CHOIR improves significance-based detection of cell types and states from single-cell data.

Cathrine Sant, Lennart Mucke, M Ryan Corces

Abstract read
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Autism Sensory Profiles Predict Stimulus- Evoked Insula Connectivity.medRxiv : the preprint server for health sciences · 2026
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  10. ThebioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Cathrine SantGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Lennart MuckeGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
M Ryan CorcesGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA. ryan.corces@gladstone.ucsf.edu.ORCID http://orcid.org/0000-0001-7465-7652

Funding

Project 4: Cross-species Dissection of Cellular Response to APOE Genotype and AD Pathology Using Single-cell Multi-omicsP01AG073082 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2021 to 2025
$23.4M
Single-cell Mapping Center for Human Regulatory Elements and Gene ActivityUM1HG012076 · NHGRI · STANFORD UNIVERSITY · PI Michael Ryan Corces, Ansuman Satpathy · 2021 to 2026
$13.8M
Multi-omic functional assessment of novel AD variants using high-throughput and single-cell technologiesU01AG072573 · NIA · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL, MONTGOMERY, STEPHEN · 2021 to 2025
$8.3M
Transcriptomic and Proteomic Analysis of Tau-dependent E/I ImbalanceR21AG085079 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2023 to 2023
$520k
NHGRI NIH HHS UM1 HG012076NIA NIH HHS P01 AG073082NIA NIH HHS R21 AG085079NIA NIH HHS U01 AG072573
6 · The paper itself

Abstract

Clustering is a critical step in the analysis of single-cell data, enabling the discovery and characterization of cell types and states. However, most popular clustering tools do not subject results to statistical inference testing, leading to risks of overclustering or underclustering data and often resulting in ineffective identification of cell types with widely differing prevalence. To address these challenges, we present CHOIR (cluster hierarchy optimization by iterative random forests), which applies a framework of random forest classifiers and permutation tests across a hierarchical clustering tree to statistically determine clusters representing distinct populations. We demonstrate the performance of CHOIR through extensive benchmarking against 15 existing clustering methods across 230 simulated and five real single-cell RNA sequencing, assay for transposase-accessible chromatin sequencing, spatial transcriptomic and multi-omic datasets. CHOIR can be applied to any single-cell data type and provides a flexible, scalable and robust solution to the challenge of identifying biologically relevant cell groupings within heterogeneous single-cell data.

Indexed as

Single-Cell AnalysisSoftwareAlgorithmsCluster AnalysisComputational BiologyGene Expression ProfilingHumansSequence Analysis, RNATranscriptome

Identifiers

PMID40195561
PMCPMC12108546

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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.