Evidence map›Paper›PMID 40404650›Full record

ArticleNature communications2025

Comprehensive evaluation of phosphoproteomic-based kinase activity inference.

Sophia Müller-Dott, Eric J Jaehnig, Khoi Pham Munchic, Wen Jiang, Tomer M Yaron-Barir, Sara R Savage, Martin Garrido-Rodriguez, Jared L Johnson, Alessandro Lussana, Evangelia Petsalaki and 7 more

Erratum issuedAbstract 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. An erratum has been issued. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
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  7. 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
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Spatial regulation of AMPK activity under oxidative stress requires LKB1.bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Sophia Müller-Dott *Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-9710-1865
Eric J Jaehnig *Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9618-6011
Khoi Pham MunchicThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Wen JiangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Tomer M Yaron-BarirMeyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Sara R SavageLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Martin Garrido-RodriguezHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-4125-5643
Jared L JohnsonDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1802-6527
Alessandro LussanaEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, UK.ORCID http://orcid.org/0000-0002-4733-0934
Evangelia PetsalakiEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, UK.ORCID http://orcid.org/0000-0002-8294-2995
Jonathan T LeiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Aurelien DugourdHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany.
Karsten KrugThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lewis C CantleyDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1298-7653
D R ManiThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3914-133X
Bing ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA. bing.zhang@bcm.edu.ORCID http://orcid.org/0000-0001-8676-2425
Julio Saez-RodriguezHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany. saezlab@ebi.ac.uk.ORCID http://orcid.org/0000-0002-8552-8976

Funding

Role of Phosphoinositides and Protein Kinases in the control of Cancer MetabolismR35CA197588 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEWIS C. CANTLEY · 2016 to 2026
$10.2M
Translating Pediatric Cancer Proteogenomic Data into Biological and Clinical InsightsU24CA271076 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Bing Zhang · 2022 to 2026
$5.0M
Center for comprehensive proteogenomic data analysisU24CA271075 · NCI · BROAD INSTITUTE, INC. · PI GAD A GETZ, Denkanikota R Mani · 2022 to 2026
$3.9M
Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RP220050NCI NIH HHS R35 CA197588NCI NIH HHS U24 CA271075NCI NIH HHS U24 CA271076Robert and Janice McNair Foundation NAU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U24-CA271076
6 · The paper itself

Abstract

Kinases regulate cellular processes and are essential for understanding cellular function and disease. To investigate the regulatory state of a kinase, numerous methods have been developed to infer kinase activities from phosphoproteomics data using kinase-substrate libraries. However, few phosphorylation sites can be attributed to an upstream kinase in these libraries, limiting the scope of kinase activity inference. Moreover, inferred activities vary across methods, necessitating evaluation for accurate interpretation. Here, we present benchmarKIN, an R package enabling comprehensive evaluation of kinase activity inference methods. Alongside classical perturbation experiments, benchmarKIN introduces a tumor-based benchmarking approach utilizing multi-omics data to identify highly active or inactive kinases. We used benchmarKIN to evaluate kinase-substrate libraries, inference algorithms and the potential of adding predicted kinase-substrate interactions to overcome the coverage limitations. Our evaluation shows most computational methods perform similarly, but the choice of library impacts the inferred activities with a combination of manually curated libraries demonstrating superior performance in recapitulating kinase activities. Additionally, in the tumor-based evaluation, adding predicted targets from NetworKIN further boosts the performance. We then demonstrate how kinase activity inference aids characterize kinase inhibitor responses in cell lines. Overall, benchmarKIN helps researchers to select reliable methods for identifying deregulated kinases.

Indexed as

PhosphoproteinsProtein KinasesProteomicsAlgorithmsBenchmarkingCell Line, TumorComputational BiologyHumansPhosphorylationProtein Kinase InhibitorsSoftwarePhosphoproteinsProtein Kinase InhibitorsProtein Kinases

Identifiers

PMID40404650
PMCPMC12098709

What OpenQuestion holds

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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.