Evidence map›Paper›PMID 39755686›Full record

ArticleNature communications2025

Segmentation aware probabilistic phenotyping of single-cell spatial protein expression data.

Yuju Lee, Edward L Y Chen, Darren C H Chan, Anuroopa Dinesh, Somaieh Afiuni-Zadeh, Conor Klamann, Alina Selega, Miralem Mrkonjic, Hartland W Jackson, Kieran R Campbell

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
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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

10 authors.

Yuju LeeLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Edward L Y ChenLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Darren C H ChanLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Anuroopa DineshLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Somaieh Afiuni-ZadehLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Conor KlamannData Sciences Institute, University of Toronto, Toronto, ON, Canada.ORCID 0009-0003-3597-8738
Alina SelegaLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.ORCID 0000-0002-8314-2922
Miralem MrkonjicDepartment of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Hartland W JacksonLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. hjackson@lunenfeld.ca.ORCID 0000-0001-6423-2415
Kieran R CampbellLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. kierancampbell@lunenfeld.ca.ORCID 0000-0003-1981-5763

Funding

Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre) PJT-175270Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) RGPIN-2020-04083
6 · The paper itself

Abstract

Spatial protein expression technologies can map cellular content and organization by simultaneously quantifying the expression of >40 proteins at subcellular resolution within intact tissue sections and cell lines. However, necessary image segmentation to single cells is challenging and error prone, easily confounding the interpretation of cellular phenotypes and cell clusters. To address these limitations, we present STARLING, a probabilistic machine learning model designed to quantify cell populations from spatial protein expression data while accounting for segmentation errors. To evaluate performance, we develop a comprehensive benchmarking workflow by generating highly multiplexed imaging data of cell line pellet standards with controlled cell content and marker expression and additionally established a score to quantify the biological plausibility of discovered cellular phenotypes on patient-derived tissue sections. Moreover, we generate spatial expression data of the human tonsil-a densely packed tissue prone to segmentation errors-and demonstrate cellular states captured by STARLING identify known cell types not visible with other methods and enable quantification of intra- and inter- individual heterogeneity.

Indexed as

Machine LearningPhenotypeSingle-Cell AnalysisCell LineHumansImage Processing, Computer-AssistedPalatine Tonsil

Identifiers

PMID39755686
PMCPMC11700195

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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.