Evidence map›Paper›PMID 40305601›Full record

ArticleScience advances2025

Massive experimental quantification allows interpretable deep learning of protein aggregation.

Mike Thompson, Mariano Martín, Trinidad Sanmartín Olmo, Chandana Rajesh, Peter K Koo, Benedetta Bolognesi, Ben Lehner

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Article
  3. amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Predicting Peptide Aggregation with Protein Language Model Embeddings.Journal of chemical information and modeling · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Dosa: A method to covalently barcode proteins for high-throughput biochemistry.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  11. PLM-eXplain: divide and conquer the protein embedding space.Bioinformatics (Oxford, England) · 2026
    Article
  12. Article
  13. Global Analysis of Aggregation Determinants in Small Protein Domains.bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Mike ThompsonCentre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.ORCID 0000-0003-1546-0512
Mariano MartínInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology, Barcelona 08028, Spain.ORCID 0000-0002-9518-2630
Trinidad Sanmartín OlmoInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
Chandana RajeshSimons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Peter K KooSimons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.ORCID 0000-0001-8722-0038
Benedetta BolognesiInstitute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology, Barcelona 08028, Spain.ORCID 0000-0002-6632-947X
Ben LehnerCentre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.ORCID 0000-0002-8817-1124

Funding

Interpretable Computational Models of Functional Genomics DataR01HG012131 · NHGRI · COLD SPRING HARBOR LABORATORY · PI Peter K Koo · 2022 to 2026
$2.1M
Reliable post hoc interpretations of deep learning in genomicsR01GM149921 · NIGMS · COLD SPRING HARBOR LABORATORY · PI Peter K Koo · 2023 to 2026
$1.7M
NHGRI NIH HHS R01 HG012131NIGMS NIH HHS R01 GM149921Wellcome Trust
6 · The paper itself

Abstract

Protein aggregation is a pathological hallmark of more than 50 human diseases and a major problem for biotechnology. Methods have been proposed to predict aggregation from sequence, but these have been trained and evaluated on small and biased experimental datasets. Here we directly address this data shortage by experimentally quantifying the aggregation of >100,000 protein sequences. This unprecedented dataset reveals the limited performance of existing computational methods and allows us to train CANYA, a convolution-attention hybrid neural network that accurately predicts aggregation from sequence. We adapt genomic neural network interpretability analyses to reveal CANYA's decision-making process and learned grammar. Our results illustrate the power of massive experimental analysis of random sequence-spaces and provide an interpretable and robust neural network model to predict aggregation.

Indexed as

Deep LearningProtein AggregatesProteinsComputational BiologyHumansNeural Networks, ComputerProtein AggregatesProteins

Identifiers

PMID40305601
PMCPMC12042874

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LicenceCC BY
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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.