Translating Proteomics

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 –

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

On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer discuss their recent experience at the 2025 US Human Proteome Organization conference or US HUPO. Their conversation covers:· The rising use of multiple proteomics platforms· Advances in multiomicsAnd· What they hope to see at the next US HUPOChapters:00:00 – Introduction01:47 – Things Parag and Andreas were most excited about going into US HUPO06:19 - Trends Parag observed at US HUPO· A bifurcation between studies that focused on measuring many proteins and those that focused on a specific biological process· People increasingly using multiomics to wholistically understanding biology as opposed to a means of comparing the different omes· A shift to researchers using multiple proteomics platforms11:44 – The rising prominence of proteoforms at US HUPO15:50 – The future of proteomics as informed by US HUPO18:06 – What Parag and Andreas hope to see at the next US HUPO19:57 - Outro

On this episode of Translating Proteomics, host Parag Mallick speaks with special guests doctors Ben Neely and Ben Orsburn, leaders in the proteomics community and hosts of “The Proteomics Show” podcast. Their insightful conversation focuses on the role of communication in proteomics and covers:· Impactful things they've learned while hosting The Proteomics Show· How their communication efforts have changed their research· Barriers to proteomics becoming more popular in the life sciences and in the broader publicChapters:00:00 – 03:04 – Intro03:04 – 07:23 – Why the Bens created "The Proteomics Show"07:23 – 10:42 – Ways the proteomics show has impacted the Bens' research10:42 – 16:44 – Every scientist is interesting!16:44 – 20:36 – Ways the Bens' communication efforts have changed their research20:36 – 25:08 – Trends in proteomics25:08 – 35:34 – Barriers to communication between the proteomics community and others in the life science34:34-48:34 - Barriers to communication between the proteomics community and the broader public48:34 - End - OutroResourcesThe Proteomics Show - Ben Neely and Ben Orsburn host this podcast sponsored by the Human Proteomics Organization. On it, they interview proteomics researchers in a “fireside chat” format. Their conversations cover not just the latest research, but also their guests' motivations, hobbies, and histories. Definitely check it out!News in Proteomics Research - Ben Orsburn's blog on the latest developments in proteomics.Proteomics, the next truly massive investment opportunity - Forbes article on the potential of proteomics.The Magic School Bus Rides Again - Recently rebooted version of The Magic School Bus. Will we see an episode featuring proteomics?

On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer discuss the many ways proteomics can impact our interactions with food. Some of the topics they touch upon in this wide-ranging conversation include:· Proteomics and food quality· Proteomics and food safety· Developing new kinds of food with proteomicsChapters00:00 – 01:23 – Introduction01:23 – 03:27 – Proteomics and alcohol fermentation03:27 – 05:24 – Food properties and their relationship with molecular composition05:24 – 07: 42 – How can we use proteoforms to improve food quality?07:42 – 11:49 – Proteomics to aid plant and animal breeding11:49 – 14:35 – Proteomics, Food Safety, and Food Security14:35 – 17:05 – Proteomics and food authenticity17:05 – 20:36 – Proteomics and terroir20:36 – 22:48 – Proteomics, the microbiome, and health22:48 – 24:29 – A fun party trick24:29 – 30:24 – Creating new foods and flavors30:24 – 34:33 – Designing food for space34:33 – End – OutroResourcesThe post-translational modification landscape of commercial beers (Kerr et al. 2021)· Paper looking at the ways post-translational modification differ between different beers and how protein content relates to the properties of foamHeat shock and structural proteins associated with meat tenderness in Nellore beef cattle, a Bos indicus breed (Carvalho et al. 2024)· Paper looking at the relationship between proteins and meat tendernessComprehensive proteome analysis of bread dicphering the allergenic potential of bread wheat, spelt and rye (Zimmermann et al. 2021)· Research measuring the levels of allergens in different kinds of breadDifferential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions· Study using proteomics to reveal how yeast adapt to growth at different temperatures

On this episode of Translating Proteomics, co-hosts Parag Mallick and Andreas Huhmer of Nautilus Biotechnology discuss the reproducibility crisis in biology and specifically focus on how we can enhance reproducibility in computational proteomics. Key topics they cover include:• What the reproducibility crisis is• Factors that make it difficult to replicate multiomics research• Steps we can take to make biology research more reproducibleChapters 00:00 – 01:20 – Introduction01:20– 03:10 – What is reproducibility in research and why is it important?03:10 – 05:42 – Recent work from the Mallick Lab focused on computational proteomics reproducibility05:42 – 09:32 – Ways to help improve reproducibility in computational proteomics – More detailed documentation, moving beyond papers as our main form of documentation, and ensuring computational workflows are available,09:32 – 11:30 – Why Parag got interested reproducibility – Attempts to build AI layers on top of current workflows11:30 – 14:00 – The need to create repositories of analytical workflows codified in a structured way that AI can learn from14:00 – 15:24 – A role for dedicated data curators15:24 – 18:31 – Moving beyond the idea of study endpoints and recognizing data as part of a larger whole18:31 – 21:32 – How does AI fit into the continuous analysis and incorporation of new datasets21:32 – 23:36 – The role of AI in helping researchers design experiments23:36 – 27:25 – Three things we can do today to increase the reproducibility of computational proteomics experiments:· Be clear about the stated hypothesis· Document analyses through workflow engines and containerized workflows· Advocate for support for funding for reproducibility and reproducibility tools27:25 – End – OutroResourcesParag's Gilbert S. Omenn Computational Proteomics Award Lectureo In this lecture, Parag describes his vision for a more reproducible future in proteomicsNature Special on “Challenges in irreproducible research”o A list of articles and perspective pieces discussing the “reproducibility crisis” in researchWhy Most Published Research Findings Are False (Ioannidis 2005)o Article outlining many of the issues that make it difficult to reproduce research findingsReproducibility Project: Cancer Biologyo eLife initiative investigating reproducibility in preclinical cancer researchCenter for Open Science Preregistration Initiativeo Resources for preregistering a hypothesis as part of a studyNational Institute of Standards and Technology (NIST)o US government agency that aims to...

On this episode of Translating Proteomics, co-hosts Parag Mallick and Andreas Huhmer of Nautilus Biotechnology discuss how clinical researchers can leverage proteomics for drug development. Some of the themes covered in this episode include:· Proteomics and pre-clinical models· How proteomics can drive patient selection· Choosing the right end points in clinical trialsChapters00:00 – 01:06 – Introduction01:06 – 06:51 – Proteomics in pre-clinical studies06:51 – 11:40 – The importance of choosing the right model for preclinical work11:40 – 17:10 – How proteomics is used in Phase I/II clinical trials17:10 – 19:29 – Proteomics tools in patient selection19:29 – 24:33 – Useful information that we get from proteomics that we can't get from genomics or transcriptomics24:33 – 28:14 – Proteomics in Phase III clinical trials and picking the best indications of drug efficacy28:14 – 29:19 - Understanding why clinical trials fail29:19 – End - Outro ResourcesThe National Cancer Institute's webpage covering how clinical trials workPreprint on the miBrain model - An example of a new in vitro brain modelGeary et al., 2021 - Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical TrialsWasko et al., 2024 - Tumour-selective activity of RAS-GTP inhibition in pancreatic cancerThe NCI-MATCH trail: Lessons for precision oncology – Report on a large-scale trial using genomic biomarkers to match cancer patients to treatmentsTumour-selective activity of RAS-GTP inhibition in pancreatic cancer – Study using proteomics to understand mechanisms of resistance to a cancer drug

On this special, year-end episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer discuss three of their favorite proteomics publications from 2024. They'll cover one paper in each of the following topic areas:Proteomics in pre-clinical researchProteomics in basic researchTechnology development in proteomicsSynopses of each of the papers can be found below and you can find many more insights in the podcast.Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomicsIn this work from Professor Bernhard Kuster's Lab at the Technical University of Munich, researchers assess protein abundance changes that result from treating Jurkat acute T cell leukemia cells with 144 drugs over five drug doses. The researchers use their proteomic data to generate millions of dose response curves for the thousands of proteins measured and discover that the drugs impact many more proteins and pathways than those identified as drug targets. In addition, they checked how 7 of the drug treatments impacted the transcriptome and found there was often discordance between impacts at the mRNA level and the protein level. This works highlights the many ways drugs can impact biological systems and suggests that similar studies will help researchers understand the effects of drug treatments and may even aid in the development of more effective or more specific therapies.Find the publication here.Natural proteome diversity links aneuploidy tolerance to protein turnoverAs we discussed on a previous episode of Translating Proteomics, genome alterations often fail to faithfully propagate to the proteome. In this work, researchers from the labs of Professor Judith Berman at Tel Aviv University and Professor Markus Ralser at the Charité - Universitätsmedizin Berlin, investigate the means through which yeast strains adapt chromosome gains or losses (aneuploidy). They assess the concordance between changes in mRNA and protein expression in aneuploid yeast that were either found in nature or generated in the lab. The researchers observed dosage compensation, a tendency to return to expression levels associated with normal chromosome numbers, for both mRNAs and proteins expressed on aneuploid chromosomes. However, dosage compensation was much stronger at the protein level than the mRNA level and even stronger at the protein level in naturally aneuploid strains compared to lab-generated strains. This work suggests that multiomics efforts are necessary to determine the effects of genomic alterations. In addition, the authors find that protein degradation, as observed through increased ubiquitination, increased turnover of proteins encoded in aneuploid chromosomes, and the up regulation of the proteasome complex, is a key means of dosage compensation. Finally, because the naturally aneuploid strains achieved a higher a level of dosage compensation than the lab-generated strains, the authors suggest there has been selection for natural aneuploid strains that down-regulate proteins causing detrimental effects.

Parag Mallick discusses the role of AI and machine learning in biotech with special guests Vijay Pande from Andreessen Horowitz and Matt McIlwain from Madrona Venture Group. Their fascinating conversation covers:Advances that have enabled biotech to make use of AI and machine learningHow founders are applying AI and machine learning in biotechThe future of AI and machine learning in biotechChapters00:00 - Introduction04:37 - How did Vijay and Matt get into AI and ML07:33 - The importance of structured data, advances in compute, and algorithmic advances in driving the boom in machine learning18:44 - The Intersection of AI and biology21:57 - The evolution of biological models31:55 - The Complexity of biological data39:42 - Ways founders and biotech startups are using AI43:25 - Favorite/Impactful applications of AI/ML47:00 - AI for experimental design50:13 - The future of AI in bio/healthResourcesLearn more about Matt McIlwainLearn more about Vijay PandeFolding at HomeLearn about various types of machine learning on IBM's websiteLearn about autoencoders on IBM's websiteLearn more about transformers on NVIDIA's blogTranslating Proteomics Episode 6 - The Future of AI in Biomedicine

On this episode of Translating Proteomics, host Andreas Huhmer discusses advances in Alzheimer's research with special guest and Curie Bio Drug Maker in Residence, Sarah DeVos Ph.D. Their conversation focuses on:The impact of molecular diagnostics on Alzheimer's researchRecent Alzheimer's drug approvalsThe future of Alzheimer's research*Small edit on Sarah's background - She did her graduate work at Washington University in St. Louis and a Postdoc at Massachusetts General Hospital*Chapters00:00 – Introduction01:54 – Why Sarah began studying Alzheimer's03:39 – Current tools and needs for future Alzheimer's diagnostics09:52 – Recent drug approvals in the Alzheimer's space and their relationship to diagnostics14:26 – Is it possible to develop biomarkers that detect Alzheimer's at its earliest stages?16:36 – What is limiting the development of new Alzheimer's biomarkers?17:51 – The DIAN trials and learnings from studying dominantly inherited Alzheimer's19:33 – The genetics of Alzheimer's22:19 – Novel approaches to identifying and understanding Alzheimer's pathology 25:54 – Where can proteomics advance Alzheimer's research?31:25 – The role of proteomics in Alzheimer's animal models34:33 – Sarah's hopes for the next 10 years of Alzheimer's research41:39 - OutroResourcesDominant Inherited Alzheimer's Network (DIAN) trials research updateso In the DIAN trials, researchers work with families to study various clinical and basic science aspects of dominantly inherited Alzheimer's disease.Amyloid plaque reducing clinical trials:o Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer's Disease (Haeberlein et al. 2022)o Donanemab in Early Symptomatic Alzheimer Disease - The TRAILBLAZER-ALZ 2 Randomized Clinical Trial (Sims et al. 2023)o Lecanemab in Early Alzheimer's Disease (Van Duck et al. 2022)Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Car (Palmqvist et al. 2024)o Clinical research into a new phospo-tau biomarker that can help physicians more effectively diagnose Alzheimer's diseaseResurrecting the Mysteries of Big Tau (Fischer and Baas 2021)o Review covering a potentially neuro-protective form of tau called “Big tau”Integrated Proteomics to Understand the Role of Neuritin (NRN1) as a Mediator of Cognitive Resilience to Alzheimer's Disease (Hurst et al. 2023)o Paper linking the NRN1 protein to cognitive resilience in...

On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer of Nautilus Biotechnology discuss the challenges and opportunities of plasma proteomics. Their conversation focuses on:· Why blood plasma may be a good source of protein biomarkers· Current methodologies and pitfalls in plasma proteomics· The path forward for plasma proteomicsWhat is Plasma Proteomics?For those who are new to this topic, plasma is the liquid portion of the blood distinct from fractions containing red and white blood cells. Given the relatively non-invasive ways physicians can collect patient plasma, and the blood's intimate association with tissues throughout the body, plasma is potentially an excellent source of protein biomarkers. Yet, it is quite difficult to measure the levels of all plasma proteins because their concentrations span over 12 orders of magnitude. This episode features an in-depth discussion of the ways plasma proteomics efforts have and have not lived up to the promise of biomarker discovery and what we can do to advance plasma biomarker discovery efforts in the future.Chapters00:00 – 01:01 – Intro01:02 – 4:55 – What is the promise of plasma proteomics?04:55 – 07:23 – Is the plasma proteome really the best source of biomarkers?07:23 – 10:16 – How do proteins get into the blood and what are the implications for biomarker discovery?10:16 – 13:59 – Is it clear that proteins are the best candidates for blood biomarkers?13:59 – 19:57 – Advances in and the future of comprehensive plasma proteomics19:57 – 22:31 – Pros and cons of fractionating the plasma proteome to discover biomarkers22:31 – 28:14 – Progress in identifying multiomic plasma biomarkers and the path forward28:14 – End – OutroResourcesNano-omics: nanotechnology-based multidimensional harvesting of the blood-circulating cancerome (Gardner et al. 2022)o Review from focused on the development multiomics liquid biopsiesMulticompartment modeling of protein shedding kinetics during vascularized tumor growth (Machiraju et al. 2020)o Work from Parag's Lab investigating tumor protein sheddingSimulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor (Frieboes et al. 2015)o Tumor protein shedding work from Parag's LabMathematical model identifies blood biomarker-based early cancer detection strategies and limitations (Hori and Gambhir et al. 2011)o Study modeling how much protein could be shed and detected from different size tumorsThe human plasma proteome: history, character, and diagnostic prospects (Anderson and Anderson 2002)o Review discussing...

Proteins adopt a wide variety of functions depending upon factors like their location in the cell, their modifications, and the biomolecules they interact with. While many of us may have been taught that single genes produce single proteins that have single functions, protein function is far more dynamic than that. In this episode of Translating Proteomics, Nautilus Co-Founder and Chief Scientist Parag Mallick sits down with University of Cambridge Professor and proteomics expert Kathryn Lilley to discuss our evolving understanding of protein function. They cover:How they came to realize protein function is more complex than one gene, one enzyme, one functionFactors that give rise to the dynamic complexity of protein function including proteoforms, protein localization, and moonlightingSteps we can take to better understand and teach others about the complexities of protein functionResearch diving into the complexities of protein functionResearch from the Beltrao Lab using bioinformatics techniques to identify functional phosphosites (Ochoa et al. 2020)Work from the Lilley Lab integrating techniques to investigate ome-wide localization of both RNA and protein (Villanueva et al. 2024)Lilley Lab preprint investigated protein localization changes in a cancer cell line as a result of ionizing radiation treatment (Christopher et al. 2024).Collaborative work with the Lundberg Lab mapping subcellular proteomics (Thul et al. 2017).Additional protein function resourcesMoonProt - A database for moonlight proteins from Professor Constance Jeffrey's LabTranslating Proteomics Episode 5 - Why the Biology Surrounding Biology's Central Dogma is Wrong

In our Translating Proteomics episode titled "Harnessing Proteoforms to Understand Life's Complexity", Parag and Andreas discussed why proteoforms are important in a theoretical sense. In this episode, Parag sits down with Northwestern University Professor and proteoform pioneer, Neil Kelleher to dive deep into the biology of proteoforms. They cover:What proteoforms areExamples of the importance of proteoformsThe scale of and technological advances needed to meet the challenges of proteoform biology.Some examples of the power of proteoforms covered in this episodeRecent work from Neil's lab showing blood proteoforms can help predict liver transplant success (Melani et al. 2022).Work form Ying Ge's lab showing changes in troponin proteoforms correlate with varying degrees of heart disease (Zhang et al. 2011).The BioTyper - a mass spectrometry-based device that can identify different kinds of microbes.Additional proteoform resourcesThe Human Proteoform Atlas webpagePublication describing The Human Proteoform Atlas (Hollas et al. 2022)Publication discussing how many human proteoforms there are (Aebersold et al. 2018)Animation - Proteoform Analysis on the Nautilus Proteome Analysis Platform

Despite incredible leaps in our understanding of molecular biology, the majority of drug development efforts still fail, and those that succeed often fail to return investment dollars. Proteomics has the potential to change that by providing high-resolution views of the biochemical drivers of biological function - proteins. In this episode of Translating Proteomics, Parag and Andreas discuss how proteomics can help researchers identify good drug targets, personalize drug development, and advance precision medicine.Chapters:00:00 - How do we define good drug targets and "druggable" in the age of proteomics08:16 - Advancing personalized medicine through proteomics10:58 - How proteomics technologies have changed drug development15:13 - New abilities next-generation proteomics technologies give us in drug developmentLearn about proteomics and biomarker discovery:https://youtu.be/8rcAxHSRGYs?si=kZ0UX42TJ8tWIaSNLearn more about proteomics and precision medicine:https://youtu.be/bzRlM45agBY?si=eop2XcGLc_oLeiVc

Proteins are far more than just the output of genes. They can be modified in myriad ways to produce millions of proteoforms with altered dynamics, localization, and function. For a comprehensive understanding of biology that will propel drug development and biomarker discovery forward, we need to be able to measure proteoforms routinely. In this episode, Parag and Andreas discuss the incredible value that will come from studying proteoforms and describe what it will take to make proteoform measurement a routine part of biology research.Chapters:00:00 - Introduction to proteoforms09:38 - Evidence that proteoforms are important and how we can use proteoform data19:28 - Technology advances needed to understand proteoform biology

AI might be the biggest buzz word of the decade, but the buzz is warranted in terms of its practical potential in biological research. In this episode of Translating Proteomics, Parag and Andreas discuss some of the early wins for AI in biology, practical ways AI can be applied to biology research in the near term, challenges in that application, and how proteomics researchers in particular can use AI to advance their work.Chapters:00:00 – Why now is the time to apply AI to biomedicine05:28 – Difficulties and potential solutions when applying AI to biology14:20 – How AI will impact the study of proteins19:34 – Risks of AI in biomedicine

From high school biology on up, we're taught the central dogma of biology - that biological information flows from DNA to RNA to proteins. This representation of the central dogma is, however, very much a simplification of its original formulation by Francis Crick and over-applying it can lead us down spurious paths and faulty conclusions. In this episode of Translating Proteomics, Parag and Andreas dive into the real meaning of the central dogma and discuss how modern biology research, including proteomics, shows we must drastically alter the ways we use and interpret the central dogma.Chapters:00:00 – What is the central dogma and how is it misinterpreted?08:06 – Regulation and control in biology11:58 – The need for new models in biology

Protein biomarkers are proteins measured as indicators of biological processes. People often hope biomarkers will take the form of elevated or decreased amounts of single proteins, but few single protein measurements provide specific and sensitive indications of biological processes. In this episode of Translating Proteomics, Parag and Andreas discuss why it is difficult to find new biomarkers and describe how new techniques can enable the development of multi-protein, multi-time point, and even multiomic biomarkers that have more potential than any single protein measurement.Learn more about biomarkers.

It's no surprise that biological systems change dramatically over space and time, but we often ignore these dynamics when comparing biological samples. In the latest episode of Translating Proteomics, Parag and Andreas discuss why it's essential to take space and time into account and envision ways we can design experiments that explicitly incorporate spacial and temporal considerations.Chapters:00:00 - Biological systems as dynamic, adaptive systems04:45 - How current experimental designs rarely take space and time into account11:54 - The tools necessary to sufficiently measure biology in space and timeSome key takeaways from the conversation:Different biological processes occur at very different time scalesComplex, multiomic interactions can only be understood over time and spaceWe need to properly collect, annotate, and share omics-level data in order to understand the rules that govern complex biology

Sure, proteomics may revolutionize precision medicine and biomarker discovery, but did you know it can help make better cheese? Listen to the latest episode of our new series, "Translating Proteomics" featuring Nautilus Co-Founder and Chief Scientist, Parag Mallick, and Nautilus Senior Director of Scientific Affairs and Alliance Management, Andreas Huhmer to learn the many ways we can put the proteome to work as the proteomics revolution begins to bear fruit.Learn more about applications of proteomicsIn this episode, Parag mentions work from Matthias Selbach's Lab. Learn more about the Selbach Lab here.

The idea to measure the proteome to get a clear understanding of healthy and diseased tissues at the molecular level has been around for many years but has not come to fruition in a broadly accessible and applicable way. In this episode we discuss:Why now is the time to make this goal a realityWhy past efforts to broadly leverage proteomics did not work outWhat we've learned from the pastWhat's changed in proteomics and science in general that makes a proteomics breakthrough possibleLearn more about proteomics