Tau proteoform analysis – Key takeaways from our recent Nature Methods publication

Translating Proteomics hosts Parag Mallick and Andreas Huhmer discuss our new Nature Methods paper, “Large-scale single-molecule analysis of tau proteoforms.” This publication describes how the Nautilus Voyager™ Platform can be used to quantify proteoforms derived from the neurodegeneration-associated tau protein. These proteoforms are defined by their unique combinations of post-translational modifications and isoform specific sequences. They may make powerful next-generation biomarkers or drug targets, but few technologies can measure them today.In the episode, Parag and Andreas discuss:What proteoforms are and why it’s critical to study them to understand biology.How the Nautilus Voyager™ Platform quantifies proteoforms.The key findings from the tau proteoform analyses in the paper.Potential applications of these findings.The Nautilus Voyager™ Platform as a powerful foundational technology.Access our video series exploring the paper in more detail.

On the latest episode of the Translating Proteomics podcast, Nautilus VP of Scientific Engagement and proteomics industry expert Sheri Wilcox joins hosts Parag Mallick and Andreas Huhmer for a thought-provoking discussion of their proteomics "hot takes.”Each “hot take” is a provocative opinion on a topic in proteomics. Specifically, they cover:Insufficient biological validation is one of the biggest problems in proteomics.Antibody validation remains a distributed, inconsistent, lab-by-lab responsibility, and this model for validation may not be sustainable going forward.AI cell models are overhyped.Check out the episode for deep explorations of each of these hot takes and their potential remedies.After listening, be sure to let us know whether you agree, disagree, or have your own hot take to share!

Professor Olga Vitek has a deep understanding of statistics, machine learning, and computational biology. She puts her know-how to work to develop computational tools enabling high-quality proteomic analysis and systems biology approaches. She hopes to apply these tools to the quantitative analysis of large-scale mass spectrometry-based investigations and thereby advance our understanding of organismal function. In this episode, Parag and Professor Vitek discuss:Why statistics is important for experimental designHow statistics and AI can help researchers understand biologyGaps keeping us from using AI and statistics to their maximum potential in biologyResourcesStatistical methods for studies of biomolecular systems websiteOlga’s personal lab websiteBeyond protein lists: AI-assisted interpretation of proteomic investigations in the context of evolving scientific knowledgeGyori and Vitek, 2024 discuss how AI can be used to interpret proteomics data and its biological meaning.A Bayesian Active Learning Experimental Design for Inferring Signaling NetworksNess et al., 2018 show how statistical methods can guide the selection of experiments that optimally enhance understanding

Host Parag Mallick chats with Professor Afshin Beheshti who is a Professor of Surgery, Director of the Center for Space Biomedicine, and Associate Director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. In addition, Professor Beheshti has a visiting researcher appointment at the Broad Institute of MIT and Harvard and is president of two non-profits – the COVID-19 International Research Team and Kwaai. The latter aims to democratize access to artificial intelligence through the design, construction, and maintenance of a free personal AI called Kwaai.Professor Beheshti’s research covers a range of topics focused on how circulating mirco RNAs and mitochondria impact health, but this conversation focuses primarily on Professor Beheshti’s work advancing our understanding of how spaceflight impacts biology. We cover:How research on spaceflight and biology is doneGaps that remain in our understanding of spaceflight and biologyOmics studies of spaceflight and biologyHow studying spaceflight and biology enhances our understanding of human health more broadlyResourcesTrivedi Institute for Space and Global BiomedicineNew Institute at the University of Pittsburgh focused on “advancing human health through space-driven innovation”NASA Open Science Data Repository"Provides open access to biological and physical science datasets from spaceflight and ground studies, enabling data reuse for discovery and innovation."Camera et al., 2024. Agining and putative frailty biomarkers are altered by spaceflightStudy on molecular biomarkers and frailty phenotypes in spaceOverbey et al., 2024. The Space Omics and Medical Atlas (SOMA) and international astronaut biobankAn “integrated data and sample repository for clinical, cellular, and multi-omic research profiles” from a variety of space missionsSpace Omics and Medical Atlas (SOMA) websiteCorti et al., 2024. To boldly go where no microRNAs have gone before: spaceflight impact on risk for small-for-gestational-age infantsExplores how miRNA signatures of “small-for-gestational-age” are impacted by the space environmentBeheshti et al., 2013. Age and space irradiation modulate tumor progression: implications for carcinogenesis riskSome of Professor Beheshti’s early work studying connections between spaceflight and cancer progression.KwaaiNonprofit "building a no-cost open source Personal AI assistant"

On this episode of Translating Proteomics, Parag and Andreas share their reflections on proteomics developments in 2025 largely inspired by their observations at the World HUPO 2025 conference in Toronto. Whether you agree, disagree, or simply want to share some of your own observations on proteomics, please post your thoughts in the comments.We look forward to even more exciting developments in 2026!Chapters00:00 - 00:35 – Intro00:36 – 07:00 - Increased focus on applications of proteomics and less on method developmentLearn more about One Health from our conversation with Professor Jennifer Geddes-McAlisterhttps://youtu.be/JFwvTdkb5bw07:01 – 12:47 - Increase in people talking about the importance of proteoformsLearn more about proteoforms in our episode featuring proteoform pioneer Professor Neil Kelleherhttps://youtu.be/3pPuxVrMxpw12:47 – 17:26 - An increase in multiomics studies17:27 – 20:03 - A shift to larger scale proteomics studiesFor a great example of a multi-platform comparison study, check out Kirsher et al., 2025https://www.nature.com/articles/s42004-025-01665-120:03 – 25:07 - Increased integration of AI into proteomics workflowsFor an example of how proteomics workflows can be modified with multiomic data, check out Suhre et al., 2025https://www.nature.com/articles/s41588-025-02413-w25:08 – 30:05 – Recognition of the need to assess quality across proteomics workflows30:06 – 32:19 – Less of a focus on spatial proteomics this year than in past years32:20 – 35: 13 - Parag and Andreas share their predictions for 202635:14 – End – Outro

On this episode of Translating Proteomics, Parag speaks with Professor Jennifer Geddes-McAlister from the University of Guelph. Professor Geddes-McAlister is an expert at using proteomics to study host-microbe interactions from a systems biology perspective. Her exciting work spans studies of pathogenic fungi all the way to engineering plants to produce pharmaceutics (so-called “molecular pharming"). On top of all that, Professor Geddes-McAlister also founded “Moms in Proteomics” to support and encourage an intentional focus on the inherently unique physical, emotional, and biological commitments of Mothers, and the ensuing balance required to excel within the diverse STEM fields encompassing Mass-Spectrometry-based proteomics. Dive into this episode to:Learn why it’s critical to study hosts, pathogens, and molecular pharming from a systems point of viewDiscover what Professor Geddes-McAlister is excited about for the upcoming Human Proteome Organization (HUPO) conferenceFind out what “Moms in Proteomics” has planned for HUPOChapters00:00 - Intro01:39 - Professor Geddes-McAlister's initial interest in host-microbe interactions06:13 - Why it's important to study host-microbe interactions08:10 - Pathogens vs helpful microbes10:06 - Thinking about microbes through the lens of "One Health" 14:34 - Why Professor Geddes-McAlister works primarily in proteomics as opposed to other omes19:44 - Professor Geddes-McAlister's favorite thing that she's learned from the proteome and couldn't learn from the other omes24:56 - Molecular pharming29:35 - The need for accessibility in proteomics34:09 - The need for all-in-one workflows in proteomics36:08 - HUPO 202539:56 - Moms in Proteomics42:36 - The future of proteomics43:59 - OutroResourcesGeddes et al., 2015. Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase Ahttps://pubmed.ncbi.nlm.nih.gov/26453029/Some of Professor Geddes-McAlister’s early work using proteomics to study pathogenic fungiPrudhomme et al., 2024. Bacterial growth-mediated systems remodelling of Nicotiana benthamiana defines unique signatures of target protein production in molecular pharminghttps://onlinelibrary.wiley.com/doi/10.1111/pbi.14342Researchers from Professor Geddes-McAlister’s lab use multiomic techniques to discover factors impacting the production of a pharmaceutical in an engineered plantWoods et al., 2023. A One Health approach to overcoming fungal disease and antifungal resistancehttps://wires.onlinelibrary.wiley.com/doi/full/10.1002/wsbm.1610Review on the importance of incorporating “One Health” principals into efforts to fight pathogenic fungiMoms in Proteomics websitehttps://momsinproteomics.caLearn all about the Moms in Proteomics initiative and its international community

On this episode of Translating Proteomics, Parag, Andreas, and special guest Don Kirkpatrick answer questions submitted by the Translating Proteomics community. They cover:Needs in plasma proteomicsHow proteomics impacts drug development – with special guest Don Kirkpatrick, Ph.D.!How lifestyle impacts the proteomeHow the Nautilus Proteome Analysis Platform is impacting tau and Alzheimer’s disease researchReferencesShome et al., 2022 - Serum autoantibodyome reveals that healthy individuals share common autoantibodieshttps://www.sciencedirect.com/science/article/pii/S2211124722006489LaBaer Lab paper investigating autoantibody levels in plasma and their relationship to health.Sylman et al., 2018 - A Temporal Examination of Platelet Counts as a Predictor of Prognosis in Lung, Prostate, and Colon Cancer Patientshttps://www.nature.com/articles/s41598-018-25019-1Mallick lab paper investigating temporal changes in platelets and their associations with cancer biology.Krönke et al., 2014 - Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cellshttps://www.science.org/doi/10.1126/science.1244851Seminal paper describing selective protein degradation caused by lenalidomide.Fink and Ebert 2015 - The novel mechanism of lenalidomide activityhttps://ashpublications.org/blood/article/126/21/2366/34644/The-novel-mechanism-of-lenalidomide-activityReview of research elucidating the mechanisms of lenalidomide activityNdoja et al., 2025 - COP1 Deficiency in BRAFV600E Melanomas Confers Resistance to Inhibitors of the MAPK Pathwayhttps://www.mdpi.com/2073-4409/14/13/975Describe links between kinase inhibitor vemurafenib and changes in ETV transcription factor degradationSong et al., 2022 - RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacyhttps://aacrjournals.org/cancerdiscovery/article/12/1/204/675622/RTK-Dependent-Inducible-Degradation-of-Mutant-PI3KUse proteomics to discover that inavolisib acts through selective degradation of mutant PI3KαCanon et al., 2019 - The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunityhttps://www.nature.com/articles/s41586-019-1694-1Covers the development of an inhibitor of KRAS mutant KRAS (G12C).Schneider et al., 2024 - Feeding gut microbes to nourish the brain: unravelling the diet-microbiota-gut-brain axishttps://www.nature.com/articles/s42255-024-01108-6Review on the gut-brain axisWebpage for Johanna Lampe’s Lab at Fred Hutch Cancer Centerhttps://www.fredhutch.org/en/faculty-lab-directory/lampe-johanna.htmlGuseh et al., 2020 - An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease riskhttps://www.nature.com/articles/s41598-020-67669-0Work investigating the relationship between exercise, the plasma proteome, and healthHuman Proteome Organization (HUPO) webpage with resources focused on proteomics in spacehttps://hupo.org/Human-Proteomics-at-Extreme-ConditionsJoly et al., 2025 - Large-scale single-molecule analysis of tau proteoformshttps://doi.org/10.1101/2025.06.26.660445Nautilus preprint using Iterative Mapping of proteoforms to measure tau proteoforms in Alzheimer’s disease and related dementias samples.

On this episode of Translating Proteomics, host Parag Mallick discusses spatial proteomics with special guest Fiona Ginty Ph.D. Fiona is a Senior Principal Scientist in Precision Diagnostics at the GE Healthcare Technology & Innovation Center. She is a leader in the development of spatial proteomics technologies and their application in precision diagnostics and medicine.Their discussion covers:·      How Fiona began working in spatial proteomics·      Why spatial biology is important·      What the future holds for spatial biologyChapters:00:00 – Introduction01:54 – Fiona’s journey to biology05:26 – Fiona’s transition to tool development07:20 – Working at GE Research11:26 – Identifying the importance of spatial biology14:43 – How Cell DIVETM works18:25 – The importance of single cell23:01 - When Fiona realized the technology worked28:04 – Spatial biology projects Fiona is excited about30:08 – Fiona’s role in HuBMAP36:50 – Learnings from HuBMAP so far38:35 – The future of spatial proteomics in the clinic46:56 – Current limits on spatial proteomics49:56 – Current and future uses of AI in spatial proteomics53:30 – The most exciting thing Fiona learned in her spatial proteomics journey56:08 – OutroResources:Method of the Year 2024: Spatial ProteomicsPaper covering the spatial proteomics technology Fiona worked on at GE HealthcareHighly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissueHubMAP – Human BioMolecular Atlas ProgramHuman Tumor Atlas NetworkCell DIVE Multiplex Imaging SolutionPapers discussing what makes colorectal cancer cells undergo apoptosis in response to chemotherapyAn atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolutionIntegrated multiplex analysis of cell death regulators in stage II colorectal cancer suggests patients with ‘persister’ cell profiles fail to benefit from adjuvant chemotherapyPaper discussing how the distance between tumor cells and cytotoxic t-cells correlates to caspase levelSpatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients - Azimi - 2024 - The Journal of Pathology - Wiley Online LibraryPaper showing it takes 3 hits from cytotoxic t-cells to kill cancer cellsCytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity | Nature CommunicationsPaper focused on generating new pathology image patches using AIPredicting Breast Cancer Events in Ductal Carcinoma In Situ (DCIS) Using Generative Adversarial Network Augmented Deep Learning Model - PubMedAcknowledgementsDr. Ginty wanted to acknowledge the many people she’s worked with on Cell DIVE and as part of HuBMAP. She stresses that these are highly collaborative projects, and just some of the many great team members she's worked with are listed below.Cell DIVE:Anup Sood, Sean Dinn, Yunxia Sui, Sanghee Cho, John Graf , Kathleen Bove, Musodiq Bello, Sudeshna Adak, Michael Lazare, Anirban Bhaduri, Thomas Treynor, Dileep Vangasseri, Alberto Santamaria-Pang, Maureen Bresnahan, Micheal Gerdes, Megan Rothman, Colin McCullough, Chris Sevinsky, Liz McDonough, Christine Surrette, Max Seel, Alex Corwin, Bob Filkins, Kevin Kenny, Brion Sarachan, Mike Montalto, Christoph Hergersberg, John Burczak, Jens Rittscher, Steve Zingelewicz, Dr. Sunil Badve (Emory U), Dr. Yesim Gokmen Polar (Emory U), Eli Lilly collaboratorsHuBMAP:Lou Falo (U. Pitt), Arivarasan Karunamurthy (U. Pitt), John Hickey (Duke), Chenchen Zhu (Stanford), Ioannis Vlachos (BIDMC), Liz McDonough (GE HealthCare Technology and Innovation Center [HTIC]), Sammi Abate (GE HealthCare Technology and Innovation Center [HTIC]), Soumya Ghose (GE HealthCare Technology and Innovation Center [HTIC]), Christine Surrette (GE HealthCare Technology and Innovation Center [HTIC]), Dr. Katy Borner (Indiana U)

On this special episode of Translating Proteomics, Parag and Andreas break down the basics of proteomics — perfect for anyone with a background in molecular biology looking to get started in the field.Seasoned experts: We hope you can share this episode as a teaching tool or to inspire others to explore proteomics.Parag and Andreas cover the following questions in the episode, and links to additional Nautilus resources can be found below each question.What is proteomics?Blog post – What is proteomics? Techniques, applications, and methodsWhat are key questions proteomics can answer?Blog category – Applications of proteomicsWhy is it important to measure the proteome?FAQ on the Nautilus Resources pageBlog post – Genomics vs. proteomics: Two complementary perspectives on lifeWhat can and can't you do with proteomics?Translating Proteomics episode – Plasma Proteomics: The Dream and the NightmareLearn how the Nautilus Platform is designed to enable comprehensive broadscale proteomics and targeted proteoform studiesWhat are key proteomics methods and techniques?Blog series – Traditional protein analysis methodsBlog series – Next-generation proteomics technologiesWhat are the major pitfalls when doing proteomics?What are the challenges in proteomic data analysis?Translating Proteomics episode – Biology in Space and TimeBlog post – What is multiomics?What are people excited about in proteomics?Translating Proteomics episode – Poised for a Proteomics BreakthroughTranslating Proteomics episode - US HUPO 2025 – Key Takeaways, Trends, and Future Directions for ProteomicsTranslating Proteomics episode – Protein Function 201 with Kathryn LilleyBlog post – What is single-molecule proteomics?

If you listened to our episode focused on science communication featuring proteomics leaders Ben Orsburn Ph.D. and Ben Neely Ph.D., then you've already heard about their excellent podcast, The Proteomics Show. On The Proteomics Show, they interview researchers in the proteomics community to learn about their motivations, their backstories, and their work. Today, we're sharing an episode of The Proteomics Show where the Bens interview Translating Proteomics host Parag Mallick. Check it out to learn about Parag's journey to proteomics, his efforts advocating for open data sharing, and his work as a professional magician.After listening, be sure to check out more episodes of The Proteomics Show on their feed where you'll find over 70 interviews with many, many interesting people in the proteomics community. Find their feed here:https://us-hupo.org/Podcasts