Mann Lab

1/3: Can MS-based proteomics see what histology can’t? We profiled 83 rare paediatric adrenocortical tumours from archival FFPE tissue & found 4 proteome-defined states that predict survival better. Now in @ebiomedicine.bsky.social, led by Rainer Claus & Andreas Metousis. doi.org/10.1016/j.eb...

doi.orgRedirecting

2/3: ~8,000 proteins per tumour. The 4 states cut across histology and stratify survival more sharply, a 5-protein classifier reproduces them, and each state shows distinct candidate vulnerabilities. A foundation for proteome-informed precision therapy.

3/3: Great collaboration across clinic and lab with Rainer Claus & Michaela Kuhlen (Universitätsklinikum Augsburg), Antje Redlich (Universitätsmedizin Magdeburg), the German MET Registry & co-authors in Giessen, Kiel, Bonn & Munich.

cell.comSPARCS enables scalable recovery of complex image-based phenotypes for genetic screeningCurrent genetic screens face a trade-off between scaling to large mutant libraries and measuring information-rich phenotypes. SPARCS automates laser microdissection to enable pooled forward genetic sc...

SPARCS: Deep Visual Proteomics-style laser microdissection meets genome-wide CRISPR screening. Find genes behind how cells look, isolate them, profile them by mass spec. Now in @cellpress.bsky.social 🎉 Congrats to @sophia-maedler.bsky.social and @nik-as.bsky.social, and all co-authors!!

Gene Center Munich @LMU Munich@genecenter-lmu.bsky.social

📢Amazing publication from the @v-hornung.bsky.social lab, in collaboration with @mannlab.bsky.social and @fabiantheis.bsky.social! They introduce SPARCS, a technology that uses AI to connect genetic perturbations with complex cellular features doi.org/10.1016/j.ce... @nik-as.bsky.social

400,000 citations! 🎉 Matthias Mann @mannlab.bsky.social just crossed this remarkable milestone on Google Scholar. From electrospray to MaxQuant to Deep Visual Proteomics, he has shaped how the world does proteomics. Congratulations from your team! #Proteomics scholar.google.com/citations?us...

That's a wrap on #HUPO2026 Singapore! 🎉 Congrats to Katherine Madden (🥇 Poster Competition), Elena Kratz (runner-up) & Kathrin Korff (Thesis Competition runner-up). And to alumni Jesper Olsen, Akhilesh Pandey & Florian Rosenberger, & to Judith Steen, on their HUPO awards! 👏

medrxiv.orgDifferentiating benign from malignant adnexal masses by biomarker-agnostic plasma proteomics using adaptive machine learningBackground: Pre-operative triage of adnexal masses with serum CA-125, HE4, and ultrasound (O-RADS) has limited accuracy, contributing to unnecessary surgery. We develop and validate a first of its kind, biomarker panel-free plasma proteomic classifier that distinguishes malignant from benign adnexal masses from a single blood draw, operating directly on discovery-mode mass spectrometry. Methods: In this multicenter prospective observational study, plasma from women with adnexal masses and from healthy controls at a large urban academic center (discovery and four validation cohorts) and an external academic center from another Urban-suburban area (external validation) was analyzed by data-independent-acquisition mass spectrometry (Orbitrap Astral), quantifying >1,000 proteins per sample. Cancerous (malignant, borderline adnexal mass, or metastasis to ovary) versus benign adnexal masses were classified with ADAPT-MS (Adaptive Diagnostic Architecture for Personalized Testing by Mass Spectrometry), which retrains an ElasticNet model for each sample based on the proteins measured. The primary outcome was discrimination (area under the receiver operating characteristic curve [AUC]). Pre-operative O-RADS scores and serum CA-125 were compared and combined with proteomics on matched subsets. Findings: Using a discovery cohort (n=1062), an ADAPT-MS classifier, validated across five independent cohorts (n=623), achieved a summary AUC of 0.835 (cohort range 0.779-0.904). Among patients with pre-operative O-RADS (n=231), proteomics (AUC 0.852) was comparable to O-RADS alone (0.863) and combining them raised discrimination to 0.922. Proteomics outperformed serum CA-125 (0.915 versus 0.777; n=125) and proteome-derived ROMA-like and two-marker surrogates. Biologically, the classification-relevant proteins are enriched for host response proteins rather than tumor cell associated protein changes, comprising ECM remodeling, complement and innate immune response pathways. This explains good detection of tumor with heterogenous pathology and also metastasis to ovary. Interpretation: A single plasma proteomic measurement interpreted using adaptive machine learning discriminates malignant from benign adnexal masses with good internal and external validation, and is complementary to ultrasound, warranting prospective evaluation as a panel-free diagnostic adjunct to imaging. ### Competing Interest Statement MM is an investor in Evosep. All other authors declare no competing interests. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Institutional Review Board at The University of Chicago and Roswell Park Cancer Institute, and informed written consent was obtained from all women participating in the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. Max Planck Society for the Advancement of Sciences NIH R35 grant Arthur and Nicole Herbst

New preprint: with ADAPT-MS, discovery plasma proteomics becomes a diagnostic tool for ovarian cancer. We separate benign from malignant adnexal masses and generalize to 5 validation cohorts. Collaboration with @lengyel-ovca-lab.bsky.social www.medrxiv.org/content/10.6...

At #HUPO2026? Come say hi to some of our @mannlab.bsky.social teammates👋 — talks & posters all week on spatial proteomics, plasma biomarkers, a human cell-type proteome atlas, interactomics & AI-driven peptide sequencing. Plenary by Matthias Mann Wed 9:00!

22 Sept

This is so well-deserved. Congratulations!

Max Planck Institute of Biochemistry@mpibiochem.bsky.social

Our director, F.-Ulrich Hartl, is receiving this year’s “Keio Medical Science Prize”. We extend our warmest congratulations to him and to the other awardee, Seishi Ogawa. ❕Press release: www.biochem.mpg.de/f-ulrich-har...

15 Sept

Proteomics analysis has always lived in its own universe. AlphaPeptTools puts it in #scverse instead, so that proteome, transcriptome and spatial data live in one ecosystem. 11 search engines (DDA+DIA) read in, proteomics-specific statistics, #scverse native. doi.org/10.64898/202...

15 Sept

Led by @brennsteiner.bsky.social and @lucas-diedrich.bsky.social, with the @scverse.bsky.social proteomics consortium. pip install alphapepttools

10 Sept

Congratulations @carolineweiss.bsky.social - fantastic work and well deserved. The future looks bright!

Max Planck Institute of Biochemistry@mpibiochem.bsky.social

Dear @carolineweiss.bsky.social, we congratulate you to your great achievement! Here´s to you and may many more follow!

1 Sept

Great job on completing your PhD 🙌. Good luck in Sweden, Max — you will do great!

Max Planck Institute of Biochemistry@mpibiochem.bsky.social

Yeah, you did it. Congratulations, Max. We wish you every success in the future and all the best in Sweden. #proteomics #PhD @mannlab.bsky.social

biorxiv.orgIn the same cell, the proteome defines cellular state and the transcriptome marks transitionsBulk transcriptome and proteome correlate only modestly, but this has not been investigated in the same cell or across cell-state changes. Here we introduce a scalable technology that quantifies thous...

27 Aug

Same single cell, two modalities—both at depth. We digest protein first, run Smart-seq3xpress + C18 (Evotip) separation: peptides captured, cDNA in flowthrough. In HeLa & stem cells, proteome tracks cell state; RNA variance flags transitioning cells. www.biorxiv.org/content/10.6...

19 Aug

Congratulations Andreas! Well done and all the best for the next steps!

Max Planck Institute of Biochemistry@mpibiochem.bsky.social

We congratulate Andreas Metousis from @mannlab.bsky.social on successfully completing his PhD. We wish you all the best for your future and your next projects. #proteomics #phd

nature.comAI proteomics: from protein identification to virtual cells - Nature MethodsThis Perspective highlights key research areas within mass spectrometry-based proteomics where AI is poised to drive significant advances.

28 July

Can AI take proteomics to a virtual cell? Our new perspective maps the path — from better peptide/protein ID to spatial & perturbation proteomics to AI Virtual Cells — and calls for an AI-friendly data ecosystem to get there. Together with Tiannan Guo and Zhang labs. www.nature.com/articles/s41...

biorxiv.orgDeep Visual Proteomics links vascular smooth muscle cell phenotypes to atherosclerotic plaque stabilityVascular smooth muscle cells (VSMCs) drive atherosclerosis through phenotypic switching, yet their spatial organization and protein signatures within plaques remain poorly characterized. Here, we appl...

17 July

New preprint: We used Deep Visual Proteomics to map vascular smooth muscle cell phenotypes in 24 human atherosclerotic plaques, cell-type & spatially resolved. Unstable plaques lose contractile and gain dedifferentiated states. www.biorxiv.org/content/10.6...

17 July

4 targets validated by siRNA knockdown. Kudos to @elenakratz.bsky.social in collaboration with Ankit Sinha & Lars Maegdefessel @tum.de

cell.comLarge-scale proteomics across neurological disorders uncovers biomarker panel and targets in multiple sclerosisDeep proteome profiling of over 5,000 cerebrospinal fluid samples by mass spectrometry maps protein alterations across major neurological disorders, resolving key sources of variation as well as share...

16 July

Congrats to all the well-deserving winners of this year's #JSPAward @mpibiochem.bsky.social and a shout-out to @carolineweiss.bsky.social and Jakob Bader for their outstanding research. www.nature.com/articles/s42... cell.com/cell/fulltex...

Max Planck Institute of Biochemistry@mpibiochem.bsky.social

Last week our very own in house award, the "Junior Scientists Publication Award" (JSPA) was presented. The best publications coming from young researchers were awarded and we congratulate them wholeheartedly - may many awards follow! 🎉

biorxiv.orgCell-type-resolved spatial proteogenomics from matched genome and proteome of the same cellsThe genome and proteome of the same cells are rarely measured together, which is especially consequential in cancer, where somatic mutations vary across clones and drive disease. We show that a single...

10 July

New preprint: Cell-type-resolved spatial proteogenomics, matched genome AND proteome of the same cells. The trick: the flowthrough we normally discard after loading peptides onto an Evotip contains genomic DNA at 85–95% yield. One tip, two molecular layers. www.biorxiv.org/content/10.6...

No new instruments, no splitting scarce sample — just collect what you'd have thrown out. Opens the door to intra-tissue pQTL analyses linking somatic mutations to their protein-level consequences.

10 July

Led by Max Zwiebel & @tnordmann.bsky.social. With @mariawahle.bsky.social, Rudolf Stadler, Mitchell Levesque and Mitchell Dummer.

Combined with Deep Visual Proteomics, this works on decades-old FFPE tissue. In melanoma we found BRAF V600E shared across cells (early driver) while NRAS Q61K & truncating CDKN2A alteration appeared only in the PRAME+ subpopulation — the known driver hierarchy, resolved in situ.

nature.comDeciphering molecular heterogeneity of carotid plaques using spatial proteomics - Nature Cardiovascular ResearchWe applied an ultra-sensitive, histomorphology-guided spatial proteomics workflow to advanced atherosclerotic carotid plaques to define molecular changes associated with minimum fibrous-cap thickness....

26 June

For those wanting the key insights without the deep methods dive, we published a research briefing in @NatureCVR nature.com/articles/s44... #SpatialProteomics #CardiovascularResearch

Mann Lab@mannlab.bsky.social

Our proteomics study of carotid plaque vulnerability is out in @natcardiovascres.nature.com — with Ankit Sinha & Lars Maegdefessel @tum.de. Our unique methodologies and integrative analysis highlight molecular and spatial diversity present in plaque tissues. www.nature.com/articles/s44...

nature.comProteomics reveals spatial and molecular heterogeneities in advanced atherosclerotic carotid artery plaques - Nature Cardiovascular ResearchAtherosclerotic plaque rupture underlies many cerebrovascular events, yet the molecular determinants of vulnerable plaque morphology remain poorly defined. Using histomorphology-guided spatial proteom...

Sample-prep tips printed with light, not packed by hand: our preprint introduces pSPEC. A robot casts 384 monolith tips at once for fast, reproducible capture-and-digest, feeding standard Evosep LC-MS. ~3,500 protein groups from urine, ~4,800 from saliva in 100 SPD. www.biorxiv.org/content/10.6...

biorxiv.orgIn situ polymerized monolith tips for reproducible, format-flexible proteomic sample preparation applied to biofluidsSample preparation increasingly sets the throughput and reproducibility of mass spectrometry (MS)-based proteomics. StageTips (stop-and-go extraction tips) and variants thereof have long been common i...

12 June

That's a wrap for ASMS 2026 for @mannlab.bsky.social team mates. The science on display was genuinely outstanding, and seeing where the field is heading has left us more motivated than ever to keep pushing our own work forward. Until next time! #ASMS2026 #MassSpectrometry #proteomics

doi.orgHIP-MS: An ultra-high-throughput, sensitive, and versatile affinity enrichment platform for static and dynamic interactome profilingAlthough protein-protein interactions govern virtually all cellular processes, systematic interactome mapping by affinity enrichment mass spectrometry (AE-MS) is constrained by manual sample preparati...

11 June

Interactome mapping has been stuck at a few hundred baits over months. HIP-MS changes the regime: ~10,000 pulldowns/week at 500 samples/day, fully automated. A new era for interactomics — and a precursor to high-throughput proteomics writ large. 📄 doi.org/10.64898/202...

31 May

At ASMS 2026? Come say hi to the MannLabs team — six talks & posters across the week on single-cell proteomics, interactome profiling, PTM enrichment, deep-learning targeted proteomics, and the latest in mass spec technology. #ASMS2026 #Proteomics #MassSpec #SingleCellProteomics

biochem.mpg.deTwo research grants to study the mechanisms of Parkinson's diseaseMatthias Mann, director at the Max Planck Institute of Biochemistry in Martinsried, Germany has received two research grants to study the mechanisms of Parkinson's disease from Aligning Science Across...

29 May

Our @MichaelJFoxOrg #ASAP grant brings the Mann lab's spatial proteomics — at single-cell-type resolution — to Parkinson's, the world's fastest-growing neurological disease. With Laura Parkkinen (Oxford University), Günter Höglinger & Franziska Hopfner (LMU Klinikum). #Proteomics

Max Planck Institute of Biochemistry@mpibiochem.bsky.social

@asapresearch.parkinsonsroadmap.org in partnership with The Michael J. Fox Foundation for Parkinson’s Research, has awarded two research grants to Matthias Mann & colleagues to investigate the mechanims underlying Parkinson's disease. ❕More: www.biochem.mpg.de/two-research... @mannlab.bsky.social

29 May

Most Parkinson's patients carry multiple overlapping pathologies. Our 2nd MichaelJFoxOrg @asapresearch.parkinsonsroadmap.org grant — with Epaminondas Doxakis (BRFAA, Athens) — will use proteomics to decode these co-pathological mechanisms. #Parkinsons #Neurodegeneration

1/5 Cell identity is written in the proteome, not in the DNA, and not always in the RNA. Out on bioRxiv today: The first cell type-resolved, MS-based proteomic atlas of the human body. www.biorxiv.org/content/10.6...

biorxiv.orgbiorxiv.org

4/5 Cell type resolution exposes biology bulk profiling misses. We find cancer-testis antigens, proteins normally restricted to immune-privileged sites and actively targeted by immunotherapies, in oocytes of the female germline. Worth noting for CTA-directed therapy safety.

v25.proteinatlas.orgDeep visual proteomics - The Human Protein Atlas

5/5 All data is integrated into @proteinatlas.bsky.social alongside matched RNA: www.proteinatlas.org/humanproteome/single+cell/dvp Shout out to Mathias Uhlen, @carolineweiss.bsky.social & a wonderful Munich–Stockholm collaboration!

biorxiv.orgbiorxiv.org

2/5 27 cell types × 14 tissues × ~14,000 proteins measured directly in tissue by Deep Visual Proteomics. The human proteome partitions into two regimes: A universal core that sustains cellular life, and tightly restricted programs that define cell type identity. Surprisingly little in between.

3/5 Matched RNA-protein comparison across 27 cell types reveals a clear rule: Concordance is organized by pathway, not by cell type. Metabolic pathways at the protein level and signaling pathways at the transcript level. A practical guide for when RNAseq predicts protein.

nature.comDeeper is not always better in plasma proteomics - Nature BiotechnologyThis Comment discusses depth, robustness and bias in plasma proteomics, concluding that increasing the depth of coverage does not necessarily translate to quantitative robustness.

22 Apr

Does identifying thousands of plasma proteins mean more biology? Not always. Over half of 210 published datasets contain contamination markers reported as disease biomarkers.

22 Apr

In our new comment @natbiotech.nature.com with Tiannan Guo, we argue: depth without quality control is artifact, not discovery. www.nature.com/articles/s41...

postdocprogram.mpg.depostdocprogram.mpg.de

We are hiring! The Matthias Mann Lab @mannlab.bsky.social @mpibiochem.bsky.social in Munich has 3 exciting #postdoc openings in proteomics & computational biology. #MSProteomics #PostDoc postdocprogram.mpg.de

3/3 Mass Spectrometry-Based Proteomics Postdoc — work at the cutting edge of MS-based biology in one of the world's leading proteomics groups! Apply → postdocprogram.mpg.de/node/43386 #MassSpec #PostDoc #Parkinson

postdocprogram.mpg.deMass Spectrometry-Based Proteomics Postdoc (m/f/div) | Max Planck Postdoc Program

postdocprogram.mpg.depostdocprogram.mpg.de

All positions are part of the @maxplanck.de #Postdoc Program — competitive pay, world-class environment, international community. Don't miss out! postdocprogram.mpg.de/all-postdoc-...

postdocprogram.mpg.depostdocprogram.mpg.de

postdocprogram.mpg.deComputational Omics Scientist -- AlphaX Proteomics Software Ecosystem (m/f/div) | Max Planck Postdoc Program

1/3 Computational Omics Scientist — join us in building the AlphaX Proteomics Software Ecosystem. Code meets biology at scale! Apply → postdocprogram.mpg.de/node/43388 #Proteomics #PostDoc

postdocprogram.mpg.deBioinformatician, Computational Postdoc - Multi-Omics Data Integration (m/f/div) | Max Planck Postdoc Program

2/3 Computational Postdoc in Multi-Omics Data Integration — if you speak protein & beyond, we want you in Munich! Apply → postdocprogram.mpg.de/node/43387 #MultiOmics #PostDoc #Parkinson

31 Mar

Big day for proteomics and in good company! Matthias Mann @mannlab.bsky.social @mpibiochem.bsky.social, John Yates and Ruedi Aebersold receive the 2026 GairdnerAwards for transforming how we measure and understand proteins at scale. #SystemsBiology #Proteomics #Gairdner2026

gairdner.org2026 Canada Gairdner Award Winners Announced2026 Canada Gairdner Awards recognize world-leading scientists for breakthrough discoveries advancing human health.

31 Mar

Congratulations to all laureates and a big shout out to fellow Max Planck Director Wolfgang Baumeister, also among the 2026 recipients — Big Day for @mpibiochem.bsky.social Incredible science being celebrated. #Gairdner2026 www.gairdner.org/resource-hub...

health.au.dkPostdoc in Computational Spatial Proteomics and Multiomics Integration - Vacancy at Aarhus UniversityVacancy at Department of Biomedicine - Forsk. & udd., Skou-bygningen, Aarhus University

23 Mar

Exciting opportunity — if you are exploring your next move, check it out and apply! health.au.dk/en/about-hea...

19 Mar

The legendary Tom Cech delivered a masterful distinguished lecture @mpibiochem.bsky.social on how RNA controls DNA. The audience was captivated! Tom's infectious energy, humility and groundbreaking science continue to inspire us all. Thanks so much for your memorable visit!

wwnorton.com/books/978132...

19 Mar

wwnorton.comThe CatalystOne of Literary Hub's Most Anticipated Books of 2024 “Lively and entertaining.… Biology will never be the same.” —Adrian Woolfson, Wall Street Journal<...