Evidence map›Paper›PMID 39039335›Full record

ArticleNature methods2024

Contextual AI models for single-cell protein biology.

Michelle M Li, Yepeng Huang, Marissa Sumathipala, Man Qing Liang, Alberto Valdeolivas, Ashwin N Ananthakrishnan, Katherine Liao, Daniel Marbach, Marinka Zitnik

Abstract read
In one paragraph

Article in Nature methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing 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

47 citing papers in PubMed.

  1. Article
  2. Review
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  8. Protein foundation models: a comprehensive survey.Science China. Life sciences · 2026
    Review
  9. Target discovery and drug design in the era of artificial intelligence.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Medea: An omics AI agent for therapeutic discovery.bioRxiv : the preprint server for biology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Michelle M LiDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Yepeng HuangDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Marissa SumathipalaDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Man Qing LiangDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Alberto ValdeolivasRoche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.ORCID http://orcid.org/0000-0001-5482-9023
Ashwin N AnanthakrishnanDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Katherine LiaoDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Daniel MarbachRoche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.ORCID http://orcid.org/0000-0002-6686-9249
Marinka ZitnikDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. marinka@hms.harvard.edu.ORCID http://orcid.org/0000-0001-8530-7228

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
VERITY: Value and Evidence in Rheumatology using bioInformaTics, and advanced analYticsP30AR072577 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Daniel Hal Solomon · 2017 to 2026
$9.8M
Determinants of inception of inflammation in inflammatory bowel diseasesR01DK127171 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ANANTHAKRISHNAN, ASHWIN N, XAVIER, RAMNIK J · 2021 to 2025
$5.4M
Measuring Neonatal RegionalizationR01HD108794 · NICHD · STANFORD UNIVERSITY · PI Jochen Profit, JEANNETTE A ROGOWSKI · 2023 to 2026
$2.8M
NHGRI NIH HHS T32 HG002295NIAMS NIH HHS P30 AR072577NICHD NIH HHS R01 HD108794NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK127171
6 · The paper itself

Abstract

Understanding protein function and developing molecular therapies require deciphering the cell types in which proteins act as well as the interactions between proteins. However, modeling protein interactions across biological contexts remains challenging for existing algorithms. Here we introduce PINNACLE, a geometric deep learning approach that generates context-aware protein representations. Leveraging a multiorgan single-cell atlas, PINNACLE learns on contextualized protein interaction networks to produce 394,760 protein representations from 156 cell type contexts across 24 tissues. PINNACLE's embedding space reflects cellular and tissue organization, enabling zero-shot retrieval of the tissue hierarchy. Pretrained protein representations can be adapted for downstream tasks: enhancing 3D structure-based representations for resolving immuno-oncological protein interactions, and investigating drugs' effects across cell types. PINNACLE outperforms state-of-the-art models in nominating therapeutic targets for rheumatoid arthritis and inflammatory bowel diseases and pinpoints cell type contexts with higher predictive capability than context-free models. PINNACLE's ability to adjust its outputs on the basis of the context in which it operates paves the way for large-scale context-specific predictions in biology.

Indexed as

Deep LearningSingle-Cell AnalysisAlgorithmsComputational BiologyHumansProtein Interaction MapsProteinsProteins

Identifiers

PMID39039335
PMCPMC11310085

What OpenQuestion holds

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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.