Florian P Bayer

Great to hear that you like it :)

To your question if that data is already in prDB - decryptM: YES it is ! e.g.
www.proteomicsdb.org/drug/107070/...

also i can recommend the interactive dashboards.html on zenodo to explore the data locally
zenodo.org/records/1609...

Very excited to see this story out in Science Signaling!!

Especially the use of dose-dependent profiling at different time points could clearly separate immediate from late and consequential signaling changes in KRAS-driven (phospho)proteomes.

Yes crazy... I still remember the 1.8 million PDF pages we were printing to manually determine what a real dose-response was in the original decryptM paper. Luckily, this is over now :)

Let me know if you need some tricks for the time-dependent hack and good luck with the paper

At the Kusterlab, we have developed a statistical analysis tool (CurveCurator) to mine these proteome-wide dose-response curves. You may want to give it a try. github.com/kusterlab/cu...
3/3

A 1.5 orders of magnitude dose range is not really wide enough for a full dose-response curve, but if you have such a scaled-up workflow, you could easily extend it to more doses with good dose resolution. 2/3

I really like the regulome-wide profiling in a dose-dependent fashion. Going one step further, I would love to see actual TF dose-response curves in Figure 5. So not interpreting each dose individually as bar, but actually have a curve with potency and efficacy estimates for each protein. 1/3

Assessment of false discovery rate control in tandem mass spectrometry analysis using entrapment - Nature Methods A theoretical foundation for entrapment methods is presented, along with a method that enables more accurate evaluation of false discovery rate (FDR) control in proteomics mass spectrometry analysis p...

Assessing error control is fundamental in mass spectrometry-based proteomics. @bo-wen.bsky.social @maccoss.bsky.social @urikeich.bsky.social et al introduce a theoretical foundation for entrapment along with a method for more accurate evaluation of FDR control.
www.nature.com/articles/s41...

I am looking forward to discuss with with you:

• (phospho)proteome-wide dose-response profiling

• statistical analysis of 180 million curves with CurveCurator

• mapping kinase-resolved activities changes due to all target engagements

• (re-)evaluating the kinase substrate space in humans

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...

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

Interesting.. that’s a long time for sure!

We are running the astral mostly without FAIMS and experienced for us normal exploris-like cleaning cycles.

It probably also means that a single publication by one group is not proving anything. Only if multiple independent groups report the same result it becomes trustworthy. Given the reproducibility crisis in biology, maybe this AI fabrication just accelerated a deeper problem, that we need to overcome

I just checked out our NAS..
there are exactly 222 active and alumni members in the folder structure. Wow quite a crowd by now :)

Achieving a 35-Plex Tandem Mass Tag Reagent Set through Deuterium Incorporation Mass spectrometry-based sample multiplexing with isobaric tags permits the development of high-throughput and precise quantitative biological assays with proteome-wide coverage and minimal missing val...

There is paper by now: (Checkout Figure 1E)

pubs.acs.org/doi/10.1021/...

It would be interesting to know what a potential company would charge.

In Europe, you pay ~ 8k for a TMT 16 plex (the 5 mg bag). This means: ~8k Eur / 50 batches / 16 samples = ~10 Eur / sample. If they could allow 5 to 2 Eur, that would be game changing.

No, I was not aware of it.. Thanks for sharing. :) .. interesting

This iTRAQ to TMT mass range should be fine and only C/N encoding. I just don't know how stable this free double bond is in the gas phase. The others always used a ring. But it's the same for all TMT channels, so maybe fine anyway.

I would always give it a try if it is cheaper, legally fine to import to Europe, and of similar isotopic/reactive quality.

But there are many small challenges to solve: bigger tags, which resolutions is needed, thermo would need to open the MS e.g custom phiSDM masses, how clean is the mz area…

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)

Also, dose-response curves yield 4 key values:

- potency -> which target caused the effect? Does it meet my expectation?

- effect size -> what is the biological response strength to the perturbation?

- direction -> is it inhibitory or activating?

- significance -> can I trust this observation?

Dose-response curves help to identify real biological signal in omics data sets because one has a clear expectation about how they should look like. Our CurveCurator software has automated this “gold digging” for everyone.

That is precisely why we are doing high-throughput, dose-dependent, (PTM)proteome-wide analyses to study MOAs of inhibitors, cell signaling, and cell adaptions.

There is such a mess in the literature caused by either low throughput or single-dose perturbation experiments. That needs to be solved!

A very nice implementation of magnetic beads based competition pull-downs with DIA readout. This workflow is well suited for real throughput …

CurveCurator is the perfect match for fast and reliable statistical analysis of these dose-response data sets.

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...

Drug synergy is a fascinating phenomenon where 1+1=3. But what molecular mechanisms drive this effect?

Our dose-resolved combination treatments with (phospho)proteome-wide readouts provide unprecedented quantitative detail of the DNA damage response.

Read more:
www.embopress.org/doi/full/10....

🎉🎉🎉

A very cool new tool to make sense out of proteome-wide perturbation data from a pathway perspective is now integrated in proteomicsDB.

Especially decryptM data can be visualized well to see drug potencies for each p-site across a pathway of proteins.

Check it out !!

CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves - Nature Communications Dose-response curves are ubiquitous in pharmacology and biology, yet potency and effect size are often estimated even when there is no response. Here, authors present a statistical framework to assess...

If your time pattern specifically looks like a sigmoidal dose-response curve and that’s the only thing you are looking for, you can also try CurveCurator. I know some folks who have done this already. Then you get statistics and FDR estimation for free.. doi.org/10.1038/s414...