Evidence map›Paper›PMID 31907444›Full record

ArticleNature methods2020

Biophysical prediction of protein-peptide interactions and signaling networks using machine learning.

Joseph M Cunningham, Grigoriy Koytiger, Peter K Sorger, Mohammed AlQuraishi

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature methods, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
5.8field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Proteome-wide prediction of interactions between structured domains and peptide motifs reveals functionally coherent subnetworks.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  6. Review
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  10. Recent progress and future challenges in structure-based protein-protein interaction prediction.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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  12. Article
  13. Article
  14. Article
  15. Article
  16. Tailored Viral-like Particles as Drivers of Medical Breakthroughs.International journal of molecular sciences · 2024
    Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Joseph M CunninghamLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1675-913X
Grigoriy KoytigerLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Peter K Sorger *Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA. peter_sorger@hms.harvard.edu.ORCID http://orcid.org/0000-0002-3364-1838
Mohammed AlQuraishi *Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA. alquraishi@hms.harvard.edu.ORCID http://orcid.org/0000-0001-6817-1322
Harvard University · USBiogen (United States) · US

Funding

TRANSLATIONAL PHARMACOLOGY COREP50GM107618 · NIGMS · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2014 to 2018
$10.8M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2018 to 2022
$10.8M
NCI NIH HHS U54 CA225088NIGMS NIH HHS P50 GM107618
6 · The paper itself

Abstract

In mammalian cells, much of signal transduction is mediated by weak protein-protein interactions between globular peptide-binding domains (PBDs) and unstructured peptidic motifs in partner proteins. The number and diversity of these PBDs (over 1,800 are known), their low binding affinities and the sensitivity of binding properties to minor sequence variation represent a substantial challenge to experimental and computational analysis of PBD specificity and the networks PBDs create. Here, we introduce a bespoke machine-learning approach, hierarchical statistical mechanical modeling (HSM), capable of accurately predicting the affinities of PBD-peptide interactions across multiple protein families. By synthesizing biophysical priors within a modern machine-learning framework, HSM outperforms existing computational methods and high-throughput experimental assays. HSM models are interpretable in familiar biophysical terms at three spatial scales: the energetics of protein-peptide binding, the multidentate organization of protein-protein interactions and the global architecture of signaling networks.

Indexed as

Machine LearningSignal TransductionBiophysical PhenomenaHumansPeptidesProtein BindingProteinsReproducibility of Resultssrc Homology DomainsPeptidesProteins

Identifiers

PMID31907444
PMCPMC7004877
OpenAlexW2997482957

What Socratic 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 Socratic graph.