Kusterlab

New preprint 🚨 We systematically measured 17 million phospho-specific dose-response curves (133 kinase inhibitors × 5 cell lines) to decrypt the kinases that shape the human phosphoproteome. We show that drug perturbation potency (not effect size) links kinases to substrates while controlling FDR.

Koina: Democratizing machine learning for proteomics research - Nature Communications Koina is an open-source, online platform that simplifies access to machine learning models in proteomics, enabling easier integration into analysis tools and helping researchers adopt and reuse ML mod...

Exited to share our latest work! Out now in @natcomms.nature.com

Koina aims to transform how #proteomics uses machine learning. You no longer need to be a tech wizard to use ML and now can easily run #ML models. Integrated with FragPipe, Skyline and EncyclopeDIA!

www.nature.com/articles/s41...

Hello Toronto!🍁The Terrific TUM Team is happy to be attending #HUPO2025. Kusterlab, Wilhelmlab and Leelab have a diverse set of presentations for you that we can't wait to share 🤓.
We're excited to spend the next days reuniting with old friends and making new connections. See you there!

Computational Approaches for Pathway‐Centric Analysis of Protein Post‐Translational Modifications Protein function is dynamically modulated by post-translational modifications (PTMs). Many different types of PTMs can nowadays be identified and quantified at a large scale using mass spectrometry. ...

Our new review paper about Pathway-Centric PTM Data Analysis is out this week in #Proteomics!
We cover databases, enrichment tools, software for pathway reconstruction, and full-fledged platforms that help to interpret high-throughput PTM datasets.
Check it out here: doi.org/10.1002/pmic...

Peptide-RNA photo-crosslinks with tunable RNA chain map protein-RNA interfaces Photo-crosslinking mass spectrometry enables the identification of protein-RNA interactions in living cells, pinpointing interaction interfaces at single-amino acid resolution. However, current isolat...

New preprint: We isolate peptide–RNA photo-crosslinks with tunable RNA chains from living cells for mass spec. This maps over 4,700 crosslinking sites across 744 proteins and offers the first glimpse into the RNA sequences in crosslinks by MS. Read here: doi.org/10.1101/2025...

Enhanced photo-crosslinking in living cells with high-intensity longwave ultraviolet light The activation of chemical reactions in living cells using ultraviolet (UV) light enables the interrogation of biomolecules in their native environment with photoreactive probes or crosslinking reagen...

New Preprint: High-intensity 365 nm irradiation accelerates photoreactions in living cells by up to 1000×. We show protein–drug 💊, –protein 💪, –DNA 🧬, –RNA 🧬 crosslinking within seconds, and analysis by #massspec for #proteomics, #chembio, #chromatin and #RNAbiology. www.biorxiv.org/content/10.1...

Thanks @tum.de for highlighting Jakob's recent paper in @cellpress.bsky.social in the university news:
www.ls.tum.de/en/ls/public...

If you haven't had the chance to read the publication, you can check it out here: doi.org/10.1016/j.ce...

Proteomic analyses identify targets, pathways, and cellular consequences of oncogenic KRAS signaling Proteomic analyses offer insights into how KRAS inhibitors affect oncogenic KRAS signaling.

If you're a KRAS nerd, get your holistic view of oncogenic KRAS signaling here: www.science.org/doi/10.1126/...
#KRAS #proteomics (4/4)

What makes it even better: All experiments were performed in a dose-resolved manner—so you can dive into dose-response curves in our interactive dashboards! #CurveCurator #BeautifulCurves (3/4)

We explore how inhibition of oncogenic KRAS signaling reshapes protein phosphorylation, ubiquitylation, and protein expression—across multiple time points, using various KRAS inhibitors, as well as upstream and downstream pathway inhibitors, in different KRAS-mutant cell lines. (2/4)

Proteomic analyses identify targets, pathways, and cellular consequences of oncogenic KRAS signaling Proteomic analyses offer insights into how KRAS inhibitors affect oncogenic KRAS signaling.

Excited to share our latest work published in #ScienceSignaling! 🚀
www.science.org/doi/10.1126/...
(1/4)

Kusterlab is looking for a new member to join our Bioinformatics team.
Apply now if you're interested in working with us!

Another day of #ASMS2025 in Baltimore, and we're back with another poster! Make sure to visit Flo today - he'll present the latest insights from his large-scale decryptM project.
Go #TeamMassSpec!

Hello Baltimore! We're looking forward to #ASMS2025 and all the new developments in mass-spec and proteomics.
If you're attending today, make sure to check out @msleelab.bsky.social's poster on citrullination in multiple sclerosis. Sophia 'Lapo' Laposchan is excited to see you there!

The human proteome with direct physical access to DNA Zero-distance photo-crosslinking reveals direct protein-DNA interactions in living cells, enabling quantitative analysis of the DNA-interacting proteome on a timescale of minutes with single-amino-aci...

🚨Our new paper is online🚨
We use zero-distance⚡photo-crosslinking⚡to reveal direct protein-DNA interactions in living cells, enabling quantitative analysis of the DNA-interacting proteome on a timescale of minutes. #DNA #Chromatin #Proteomics
www.cell.com/cell/fulltex...

New paper!
Our chemoproteomic survey of phenylhydroxamic acids identifies the first drug-like inhibitors for nucleotide-binding protein HINT1 and nucleoside kinases NME1-4. On top, we found probes for the HDAC inhibitor off-target MBLAC2. Check out the open-access article! tinyurl.com/yh92vh6b

sev on X: "Paper alert! We report the first inhibitors for nucleoside kinases NME1-4 and for the nucleotide-binding protein HINT1. On top, we provide probes for MBLAC2, an off-target of every second (!) hydroxamic acid-based HDAC inhibitor! https://t.co/uuRCO78xFz 👇🧵" / X Paper alert! We report the first inhibitors for nucleoside kinases NME1-4 and for the nucleotide-binding protein HINT1. On top, we provide probes for MBLAC2, an off-target of every second (!) hydroxamic acid-based HDAC inhibitor! https://t.co/uuRCO78xFz 👇🧵

New paper!
Our chemoproteomic survey of phenylhydroxamic acids identifies the first drug-like inhibitors for nucleotide-binding protein HINT1 and nucleoside kinases NME1-4. On top, we found probes for the HDAC inhibitor off-target MBLAC2. Check out the open-access article! tinyurl.com/yh92vh6b

Unifying the analysis of bottom-up proteomics data with CHIMERYS - Nature Methods CHIMERYS is a spectrum-centric and data acquisition method-agnostic algorithm for the analysis of MS2 spectra. It is capable of deconvoluting any MS2 spectrum, regardless of whether it was acquired by...

One algorithm to rule them all? CHIMERYS bridges the gap — DDA,DIA and PRM — together at last!
With #CHIMERYS, we can now directly compare DDA and DIA data — 🍎 to 🍎 finally made possible.
doi.org/10.1038/s41592-025-02663-w
#KusterLab #WilhelmLab #MSAID #Proteomics

3/2025 Issue ➡️ www.embopress.org/toc/17444292...
metabolic mutations drive bacterial antibiotic resistance evolution, prior knowledge for GRN inference, HPA drugs fail mood disorder clinical trials

Cover: ATR kinase inhibitors work together to overcome chemoresistance @kusterlab.bsky.social

Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response | Molecular Systems Biology imageimagePhosphoproteomics unveils the mode of action of clinical ATR inhibitors and explains their synergy with Gemcitabine in pancreatic cancer cells. Viability screening of 146 targeted drugs ide...

📢 Read the full paper here: doi.org/10.1038/s44320-025-00085-6 – we’d love to hear your thoughts! #CancerResearch #PDAC #MolecularBiology #Proteomics (4/4)

🔎 To uncover the molecular mechanisms driving this synergy, we employed both chemo- and phosphoproteomics (decryptM), which revealed how ATR inhibition disrupts the DNA damage response when combined with gemcitabine. (3/4)

🧫 Using large-scale phenotypic drug screening, we identified promising drug combinations that enhance tumor cell death - and found Gemcitabine and ATR inhibitors to synergize most effectively. (2/4)

Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response | Molecular Systems Biology imageimagePhosphoproteomics unveils the mode of action of clinical ATR inhibitors and explains their synergy with Gemcitabine in pancreatic cancer cells. Viability screening of 146 targeted drugs ide...

🚀 Exciting news from our lab! Our latest paper has been featured on the cover of @molsystbiol.org - "Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response" by Höfer et al.! 🧬🎉 doi.org/10.1038/s44320-025-00085-6 (1/4)

We'll DM you

Our tool was built using Vue.js and D3.js and is free for public reuse (github.com/kusterlab/bi..., github.com/wilhelm-lab/...).
Thanks to everyone involved! 🥳 We're looking forward to seeing how it'll be received by the community. (6/6).

If canonical pathway diagrams are not enough for you, just build your own! PTMNavigator's editing mode allows you to design custom pathways, tailored to your data and research question. 🧑‍🔬 (5/6)

What's more, we developed a server that runs various enrichment analyses on your data (github.com/kusterlab/en...) 🤓. The results of this are automatically integrated into PTMNavigator and help you figure out which pathways, proteins and PTM signatures are potentially relevant for your dataset.(4/6)

PTMNavigator projects your data onto interactive pathway diagrams, showing you where the hotspots of PTM regulation are. 🗺️ 📍 This can be used, for example, to contrast how two drugs affect the same pathway at different stages. (3/6)

Putting PTM data into context can be a daunting task, and it's easy to lose sight of the big picture. 👀
To tackle this, Julian Müller and colleagues have developed PTMNavigator, which is available at ProteomicsDB 💻 www.proteomicsdb.org/analytics/ptmNavigator (2/6)

PTMNavigator: interactive visualization of differentially regulated post-translational modifications in cellular signaling pathways - Nature Communications Post-translational modifications are important regulators of cellular pathways, but our understanding of these processes is limited. Here, the authors present a web tool that integrates various databa...

🎉 We're happy to announce that our latest project was published in @naturecomms.bsky.social this week: PTMNavigator, a #bioinformatics web platform for in-depth analysis of post-translational modification (PTM) perturbation datasets.
📄 doi.org/10.1038/s414... (1/6)