Evidence map›Paper›PMID 36050488›Full record

ArticleNature methods2022

Cell type-specific inference of differential expression in spatial transcriptomics.

Dylan M Cable, Evan Murray, Vignesh Shanmugam, Simon Zhang, Luli S Zou, Michael Diao, Haiqi Chen, Evan Z Macosko, Rafael A Irizarry, Fei Chen

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed
14.5field-weighted citation impact, top 1% 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

119 citing papers in PubMed, 158 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Investigating Spatial Dynamics in Spatial Omics Data with StarTrail.Journal of the American Statistical Association · 2026
    Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

59 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

10 authors at 2 institutions in 1 country.

Dylan M CableDepartment of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.
Evan MurrayBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Vignesh ShanmugamBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Simon ZhangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Luli S ZouBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael DiaoDepartment of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5592-4556
Haiqi ChenBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Evan Z MacoskoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2794-5165
Rafael A Irizarry *Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA. rafa@ds.dfci.harvard.edu.ORCID http://orcid.org/0000-0002-3944-4309
Fei Chen *Broad Institute of MIT and Harvard, Cambridge, MA, USA. chenf@broadinstitute.org.ORCID http://orcid.org/0000-0003-2308-3649
Broad Institute · USHarvard University · US

Funding

UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI JONATHAN Charles COHEN · 2022 to 2026
$7.4M
COVID19 Slide-seqR01HG010647 · NHGRI · BROAD INSTITUTE, INC. · PI Fei Chen, Evan Z Macosko · 2019 to 2026
$6.0M
Data Analysis Tools for Emerging High-Throughput TechnologiesR35GM131802 · NIGMS · DANA-FARBER CANCER INST · PI Rafael Angel Irizarry · 2019 to 2026
$4.1M
Overcoming bias and unwanted variability in next generation sequencingR01HG005220 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2010 to 2018
$3.6M
Next Generation Computational Tools for Functional GenomicsR01HG011139 · NHGRI · DANA-FARBER CANCER INST · PI IRIZARRY, RAFAEL ANGEL · 2020 to 2024
$3.5M
Characterizing glioma heterogeneity with novel multiplexed nanoscale imaging technologiesDP5OD024583 · OD · BROAD INSTITUTE, INC. · PI CHEN, FEI · 2017 to 2021
$2.2M
IMAT-ITCR Collaboration: An integrated experimental and computational platform for analyzing the spatial organization of tumor clonesR33CA246455 · NCI · BROAD INSTITUTE, INC. · PI ASHENBERG, ORR, CHEN, FEI · 2020 to 2022
$1.4M
NCI NIH HHS R33 CA246455NHGRI NIH HHS R01 HG005220NHGRI NIH HHS R01 HG010647NHGRI NIH HHS R01 HG011139NIDDK NIH HHS P30 DK127984NIGMS NIH HHS R35 GM131802NIH HHS DP5 OD024583
6 · The paper itself

Abstract

A central problem in spatial transcriptomics is detecting differentially expressed (DE) genes within cell types across tissue context. Challenges to learning DE include changing cell type composition across space and measurement pixels detecting transcripts from multiple cell types. Here, we introduce a statistical method, cell type-specific inference of differential expression (C-SIDE), that identifies cell type-specific DE in spatial transcriptomics, accounting for localization of other cell types. We model gene expression as an additive mixture across cell types of log-linear cell type-specific expression functions. C-SIDE's framework applies to many contexts: DE due to pathology, anatomical regions, cell-to-cell interactions and cellular microenvironment. Furthermore, C-SIDE enables statistical inference across multiple/replicates. Simulations and validation experiments on Slide-seq, MERFISH and Visium datasets demonstrate that C-SIDE accurately identifies DE with valid uncertainty quantification. Last, we apply C-SIDE to identify plaque-dependent immune activity in Alzheimer's disease and cellular interactions between tumor and immune cells. We distribute C-SIDE within the R package https://github.com/dmcable/spacexr .

Indexed as

Gene Expression ProfilingTranscriptome

Identifiers

PMID36050488
PMCPMC10463137
OpenAlexW4294053500

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.