Translating Proteomics

AI and Statistics in Proteomics and Systems Biology

Wed, 25 Feb 2026 09:00:00 -0800

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 design
How statistics and AI can help researchers understand biology
Gaps keeping us from using AI and statistics to their maximum potential in biology

Resources

Statistical methods for studies of biomolecular systems website

Olga’s personal lab website

Beyond protein lists: AI-assisted interpretation of proteomic investigations in the context of evolving scientific knowledge

Gyori 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 Networks

Ness et al., 2018 show how statistical methods can guide the selection of experiments that optimally enhance understanding

OMICS IN SPACE

Wed, 04 Feb 2026 09:00:00 -0800

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 done
Gaps that remain in our understanding of spaceflight and biology
Omics studies of spaceflight and biology
How studying spaceflight and biology enhances our understanding of human health more broadly

Resources

Trivedi Institute for Space and Global Biomedicine

New 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 spaceflight

Study on molecular biomarkers and frailty phenotypes in space

Overbey et al., 2024. The Space Omics and Medical Atlas (SOMA) and international astronaut biobank

An “integrated data and sample repository for clinical, cellular, and multi-omic research profiles” from a variety of space missions
Space Omics and Medical Atlas (SOMA) website

Corti et al., 2024. To boldly go where no microRNAs have gone before: spaceflight impact on risk for small-for-gestational-age infants

Explores how miRNA signatures of “small-for-gestational-age” are impacted by the space environment

Beheshti et al., 2013. Age and space irradiation modulate tumor progression: implications for carcinogenesis risk

Some of Professor Beheshti’s early work studying connections between spaceflight and cancer progression.

Kwaai

Nonprofit "building a no-cost open source Personal AI assistant"

Reflections on Proteomics - 2025 Yea-End Wrap-Up

Mon, 22 Dec 2025 09:00:00 -0800

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!

Chapters

00:00 - 00:35 – Intro

00:36 – 07:00 - Increased focus on applications of proteomics and less on method development

Learn more about One Health from our conversation with Professor Jennifer Geddes-McAlister

https://youtu.be/JFwvTdkb5bw

07:01 – 12:47 - Increase in people talking about the importance of proteoforms

Learn more about proteoforms in our episode featuring proteoform pioneer Professor Neil Kelleher

https://youtu.be/3pPuxVrMxpw

12:47 – 17:26 - An increase in multiomics studies

17:27 – 20:03 - A shift to larger scale proteomics studies

For a great example of a multi-platform comparison study, check out Kirsher et al., 2025

https://www.nature.com/articles/s42004-025-01665-1

20:03 – 25:07 - Increased integration of AI into proteomics workflows

For an example of how proteomics workflows can be modified with multiomic data, check out Suhre et al., 2025

https://www.nature.com/articles/s41588-025-02413-w

25:08 – 30:05 – Recognition of the need to assess quality across proteomics workflows

30:06 – 32:19 – Less of a focus on spatial proteomics this year than in past years

32:20 – 35: 13 - Parag and Andreas share their predictions for 2026

35:14 – End – Outro

Hosts, Microbes, Molecular Pharming, and More with Professor Jennifer Geddes-McAlister

Thu, 06 Nov 2025 09:00:00 -0800

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 view
Discover what Professor Geddes-McAlister is excited about for the upcoming Human Proteome Organization (HUPO) conference
Find out what “Moms in Proteomics” has planned for HUPO

Chapters

00:00 - Intro

01:39 - Professor Geddes-McAlister's initial interest in host-microbe interactions

06:13 - Why it's important to study host-microbe interactions

08:10 - Pathogens vs helpful microbes

10:06 - Thinking about microbes through the lens of "One Health"

14:34 - Why Professor Geddes-McAlister works primarily in proteomics as opposed to other omes

19:44 - Professor Geddes-McAlister's favorite thing that she's learned from the proteome and couldn't learn from the other omes

24:56 - Molecular pharming

29:35 - The need for accessibility in proteomics

34:09 - The need for all-in-one workflows in proteomics

36:08 - HUPO 2025

39:56 - Moms in Proteomics

42:36 - The future of proteomics

43:59 - Outro

Resources

Geddes et al., 2015. Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A

https://pubmed.ncbi.nlm.nih.gov/26453029/

Some of Professor Geddes-McAlister’s early work using proteomics to study pathogenic fungi

Prudhomme et al., 2024. Bacterial growth-mediated systems remodelling of Nicotiana benthamiana defines unique signatures of target protein production in molecular pharming

https://onlinelibrary.wiley.com/doi/10.1111/pbi.14342

Researchers from Professor Geddes-McAlister’s lab use multiomic techniques to discover factors impacting the production of a pharmaceutical in an engineered plant

Woods et al., 2023. A One Health approach to overcoming fungal disease and antifungal resistance

https://wires.onlinelibrary.wiley.com/doi/full/10.1002/wsbm.1610

Review on the importance of incorporating “One Health” principals into efforts to fight pathogenic fungi

Moms in Proteomics website

https://momsinproteomics.ca

Learn all about the Moms in Proteomics initiative and its international community

“Ask me anything” with Parag Mallick, Andreas Huhmer, and featuring special guest Don Kirkpatrick, Ph.D.

Tue, 15 Jul 2025 09:00:00 -0800

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 proteomics
How proteomics impacts drug development – with special guest Don Kirkpatrick, Ph.D.!
How lifestyle impacts the proteome
How the Nautilus Proteome Analysis Platform is impacting tau and Alzheimer’s disease research

References

Shome et al., 2022 - Serum autoantibodyome reveals that healthy individuals share common autoantibodies

https://www.sciencedirect.com/science/article/pii/S2211124722006489

LaBaer 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 Patients

https://www.nature.com/articles/s41598-018-25019-1

Mallick 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 cells

https://www.science.org/doi/10.1126/science.1244851

Seminal paper describing selective protein degradation caused by lenalidomide.

Fink and Ebert 2015 - The novel mechanism of lenalidomide activity

https://ashpublications.org/blood/article/126/21/2366/34644/The-novel-mechanism-of-lenalidomide-activity

Review of research elucidating the mechanisms of lenalidomide activity

Ndoja et al., 2025 - COP1 Deficiency in BRAFV600E Melanomas Confers Resistance to Inhibitors of the MAPK Pathway

https://www.mdpi.com/2073-4409/14/13/975

Describe links between kinase inhibitor vemurafenib and changes in ETV transcription factor degradation

Song et al., 2022 - RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy

https://aacrjournals.org/cancerdiscovery/article/12/1/204/675622/RTK-Dependent-Inducible-Degradation-of-Mutant-PI3K

Use proteomics to discover that inavolisib acts through selective degradation of mutant PI3Kα

Canon et al., 2019 - The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity

https://www.nature.com/articles/s41586-019-1694-1

Covers 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 axis

https://www.nature.com/articles/s42255-024-01108-6

Review on the gut-brain axis

Webpage for Johanna Lampe’s Lab at Fred Hutch Cancer Center

https://www.fredhutch.org/en/faculty-lab-directory/lampe-johanna.html

Guseh et al., 2020 - An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease risk

https://www.nature.com/articles/s41598-020-67669-0

Work investigating the relationship between exercise, the plasma proteome, and health

Human Proteome Organization (HUPO) webpage with resources focused on proteomics in space

https://hupo.org/Human-Proteomics-at-Extreme-Conditions

Joly et al., 2025 - Large-scale single-molecule analysis of tau proteoforms

https://doi.org/10.1101/2025.06.26.660445

Nautilus preprint using Iterative Mapping of proteoforms to measure tau proteoforms in Alzheimer’s disease and related dementias samples.

Spatial Proteomics with Fiona Ginty Ph.D.

Wed, 28 May 2025 09:00:00 -0800

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 biology

Chapters:

00:00 – Introduction

01:54 – Fiona’s journey to biology

05:26 – Fiona’s transition to tool development

07:20 – Working at GE Research

11:26 – Identifying the importance of spatial biology

14:43 – How Cell DIVETM works

18:25 – The importance of single cell

23:01 - When Fiona realized the technology worked

28:04 – Spatial biology projects Fiona is excited about

30:08 – Fiona’s role in HuBMAP

36:50 – Learnings from HuBMAP so far

38:35 – The future of spatial proteomics in the clinic

46:56 – Current limits on spatial proteomics

49:56 – Current and future uses of AI in spatial proteomics

53:30 – The most exciting thing Fiona learned in her spatial proteomics journey

56:08 – Outro

Resources:

Method of the Year 2024: Spatial Proteomics

Paper covering the spatial proteomics technology Fiona worked on at GE Healthcare

Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue

HubMAP – Human BioMolecular Atlas Program

Human Tumor Atlas Network

Cell DIVE Multiplex Imaging Solution

Papers discussing what makes colorectal cancer cells undergo apoptosis in response to chemotherapy

Paper discussing how the distance between tumor cells and cytotoxic t-cells correlates to caspase level

Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients - Azimi - 2024 - The Journal of Pathology - Wiley Online Library

Paper showing it takes 3 hits from cytotoxic t-cells to kill cancer cells

Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity | Nature Communications

Paper focused on generating new pathology image patches using AI

Predicting Breast Cancer Events in Ductal Carcinoma In Situ (DCIS) Using Generative Adversarial Network Augmented Deep Learning Model - PubMed

Acknowledgements

Dr. 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 collaborators

HuBMAP:

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)

Intro to Proteomics

Wed, 16 Apr 2025 09:00:00 -0800

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 methods

What are key questions proteomics can answer?

Blog category – Applications of proteomics

Why is it important to measure the proteome?

FAQ on the Nautilus Resources page
Blog post – Genomics vs. proteomics: Two complementary perspectives on life

What can and can't you do with proteomics?

Translating Proteomics episode – Plasma Proteomics: The Dream and the Nightmare
Learn how the Nautilus Platform is designed to enable comprehensive broadscale proteomics and targeted proteoform studies

What are key proteomics methods and techniques?

Blog series – Traditional protein analysis methods
Blog series – Next-generation proteomics technologies

What are the major pitfalls when doing proteomics?

What are the challenges in proteomic data analysis?

Translating Proteomics episode – Biology in Space and Time
Blog post – What is multiomics?

What are people excited about in proteomics?

Translating Proteomics episode – Poised for a Proteomics Breakthrough
Translating Proteomics episode - US HUPO 2025 – Key Takeaways, Trends, and Future Directions for Proteomics
Translating Proteomics episode – Protein Function 201 with Kathryn Lilley
Blog post – What is single-molecule proteomics?

Proteomics Podcast Crossover - The Proteomics Show

Wed, 02 Apr 2025 09:00:00 -0800

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

US HUPO 2025 - Key Takeaways, Trends, and Future Directions for Proteomics

Wed, 26 Mar 2025 09:00:00 -0800

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 multiomics

And

· What they hope to see at the next US HUPO

Chapters:

00:00 – Introduction

01:47 – Things Parag and Andreas were most excited about going into US HUPO

06:19 - 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 platforms

11:44 – The rising prominence of proteoforms at US HUPO

15:50 – The future of proteomics as informed by US HUPO

18:06 – What Parag and Andreas hope to see at the next US HUPO

19:57 - Outro

Science Communication and Proteomics - Benefits, Barriers, and Solutions with Ben Neely and Ben Orsburn

Wed, 19 Feb 2025 09:00:00 -0800

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 public

Chapters:

00:00 – 03:04 – Intro

03:04 – 07:23 – Why the Bens created "The Proteomics Show"

07:23 – 10:42 – Ways the proteomics show has impacted the Bens’ research

10:42 – 16:44 – Every scientist is interesting!

16:44 – 20:36 – Ways the Bens' communication efforts have changed their research

20:36 – 25:08 – Trends in proteomics

25:08 – 35:34 – Barriers to communication between the proteomics community and others in the life science

34:34-48:34 - Barriers to communication between the proteomics community and the broader public

48:34 - End - Outro

Resources

The 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?

The Future of Food in a Proteomics World

Wed, 05 Feb 2025 09:00:00 -0800

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 proteomics

Chapters

00:00 – 01:23 – Introduction

01:23 – 03:27 – Proteomics and alcohol fermentation

03:27 – 05:24 – Food properties and their relationship with molecular composition

05:24 – 07: 42 – How can we use proteoforms to improve food quality?

07:42 – 11:49 – Proteomics to aid plant and animal breeding

11:49 – 14:35 – Proteomics, Food Safety, and Food Security

14:35 – 17:05 – Proteomics and food authenticity

17:05 – 20:36 – Proteomics and terroir

20:36 – 22:48 – Proteomics, the microbiome, and health

22:48 – 24:29 – A fun party trick

24:29 – 30:24 – Creating new foods and flavors

30:24 – 34:33 – Designing food for space

34:33 – End – Outro

Resources

The 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 foam

Heat 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 tenderness

Comprehensive 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 bread

Differential 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

Combating the Reproducibility Crisis in Computational Proteomics

Wed, 22 Jan 2025 09:00:00 -0800

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 reproducible

Chapters

00:00 – 01:20 – Introduction

01:20– 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 reproducibility

05:42 – 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 workflows

11:30 – 14:00 – The need to create repositories of analytical workflows codified in a structured way that AI can learn from

14:00 – 15:24 – A role for dedicated data curators

15:24 – 18:31 – Moving beyond the idea of study endpoints and recognizing data as part of a larger whole

18:31 – 21:32 – How does AI fit into the continuous analysis and incorporation of new datasets

21:32 – 23:36 – The role of AI in helping researchers design experiments

23:36 – 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 tools

27:25 – End – Outro

Resources

Parag’s Gilbert S. Omenn Computational Proteomics Award Lecture

o In this lecture, Parag describes his vision for a more reproducible future in proteomics

Nature Special on “Challenges in irreproducible research”

o A list of articles and perspective pieces discussing the “reproducibility crisis” in research

Why Most Published Research Findings Are False (Ioannidis 2005)

o Article outlining many of the issues that make it difficult to reproduce research findings

Reproducibility Project: Cancer Biology

o eLife initiative investigating reproducibility in preclinical cancer research

Center for Open Science Preregistration Initiative

o Resources for preregistering a hypothesis as part of a study

National Institute of Standards and Technology (NIST)

o US government agency that aims to be “the world’s leader in creating critical measurement solutions and promoting equitable standards.”

MSstats

o Open source software for mass spec data analysis from Bioconductor

National Institute of General Medical Sciences

o US government agency focused on “basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment, and prevention.”

Chan Zuckerberg Initiative – Essential Open Source Software for Science

o CZI program supporting “software maintenance, growth, development, and community engagement for critical open source tools.”

Expanding the Drug Development Toolkit with Proteomics

Wed, 08 Jan 2025 16:00:00 -0800

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 trials

Chapters

00:00 – 01:06 – Introduction

01:06 – 06:51 – Proteomics in pre-clinical studies

06:51 – 11:40 – The importance of choosing the right model for preclinical work

11:40 – 17:10 – How proteomics is used in Phase I/II clinical trials

17:10 – 19:29 – Proteomics tools in patient selection

19:29 – 24:33 – Useful information that we get from proteomics that we can’t get from genomics or transcriptomics

24:33 – 28:14 – Proteomics in Phase III clinical trials and picking the best indications of drug efficacy

28:14 – 29:19 - Understanding why clinical trials fail

29:19 – End - Outro

Resources

The National Cancer Institute’s webpage covering how clinical trials work
Preprint on the miBrain model - An example of a new in vitro brain model
Geary et al., 2021 - Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
Wasko et al., 2024 - Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer
The NCI-MATCH trail: Lessons for precision oncology – Report on a large-scale trial using genomic biomarkers to match cancer patients to treatments
Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer – Study using proteomics to understand mechanisms of resistance to a cancer drug

2024 Year-End Special: 3 Exciting Examples of Proteomics Research

Wed, 18 Dec 2024 15:00:00 -0800

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 research
Proteomics in basic research
Technology development in proteomics

Synopses 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 proteomics

In 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 turnover

As 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 to 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 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.

Find the publication here.

Multi-pass, single-molecule nanopore reading of long protein strands

Single-molecule protein sequencing is a long sought after goal of the proteomics field. Nanopore-based sequencers thread single protein molecules through tiny pores imbedded in membranes. Changes in the electrical properties of the pores due to protein threading can theoretically be measured to sequence the threaded proteins. To date, the complex signals coming from full protein molecules cannot be effectively interpreted to determine complete protein sequences. In this work from Professor Jeff Nivala’s lab at the University of Washington, researchers bring the field one step closer to full protein sequencing by showing they can use nanopore-based devices to effectively conduct long reads and identify single amino acid substitutions in repetitive protein sequences with otherwise highly similar readouts. In addition, they develop a method that makes it possible to conduct repeated reads of the same protein molecule and thereby improve read accuracy. They leverage their methodology to show they can design protein barcodes, identify PTMs on otherwise identical protein molecules, and identify traces indicative of particular proteins. While they do not sequence full proteins, these researchers suggest their techniques can be used for proteoform identification and the creation of millions to billions of individually distinguishable barcodes.

Find the publication here.

Additional exciting work in proteomics from 2024

While not discussed in this podcast, Parag and Andreas also loved the papers listed below. Do you have any favorites that aren’t featured here? Please share them in the comments or email them to us at translatingproteomics@nautilus.bio. We can’t wait to hear from you.

Additional favorites from Parag and Andreas:

· Exploring structural diversity across the protein universe with the Encyclopedia of Domains

· Atlas of the plasma proteome in health and disease in 53,026 adults

· Integrating multiplexed imaging and multiscale modeling identifies tumor phenotype conversion as a critical component of therapeutic T cell efficacy

· Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection

AI and Biotech - The Promise and the Pitfalls with Matt McIlwain and Vijay Pande

Wed, 04 Dec 2024 09:00:00 -0800

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 learning
How founders are applying AI and machine learning in biotech
The future of AI and machine learning in biotech

Chapters

00:00 - Introduction

04:37 - How did Vijay and Matt get into AI and ML

07:33 - The importance of structured data, advances in compute, and algorithmic advances in driving the boom in machine learning

18:44 - The Intersection of AI and biology

21:57 - The evolution of biological models

31:55 - The Complexity of biological data

39:42 - Ways founders and biotech startups are using AI

43:25 - Favorite/Impactful applications of AI/ML

47:00 - AI for experimental design

50:13 - The future of AI in bio/health

Resources

A New Era In Alzheimer's Research with Sarah DeVos

Wed, 30 Oct 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 research
Recent Alzheimer’s drug approvals
The 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*

Chapters

00:00 – Introduction

01:54 – Why Sarah began studying Alzheimer’s

03:39 – Current tools and needs for future Alzheimer’s diagnostics

09:52 – Recent drug approvals in the Alzheimer’s space and their relationship to diagnostics

14:26 – 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’s

19:33 – The genetics of Alzheimer’s

22:19 – 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 models

34:33 – Sarah’s hopes for the next 10 years of Alzheimer’s research

41:39 - Outro

Resources

Dominant Inherited Alzheimer’s Network (DIAN) trials research updates

o 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 disease

Resurrecting 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 Alzheimer’s

o Nautilus blog post about this paper

Plasma Proteomics - The Dream and the Nightmare

Mon, 28 Oct 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 proteomics

What 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.

Chapters

00:00 – 01:01 – Intro

01:02 – 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 proteomics

19:57 – 22:31 – Pros and cons of fractionating the plasma proteome to discover biomarkers

22:31 – 28:14 – Progress in identifying multiomic plasma biomarkers and the path forward

28:14 – End – Outro

Resources

Nano-omics: nanotechnology-based multidimensional harvesting of the blood-circulating cancerome (Gardner et al. 2022)

o Review from focused on the development multiomics liquid biopsies

Multicompartment modeling of protein shedding kinetics during vascularized tumor growth (Machiraju et al. 2020)

o Work from Parag’s Lab investigating tumor protein shedding

Simulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor (Frieboes et al. 2015)

o Tumor protein shedding work from Parag’s Lab

Mathematical 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 tumors

The human plasma proteome: history, character, and diagnostic prospects (Anderson and Anderson 2002)

o Review discussing the clinical importance of the plasma proteome and the wide range of protein abundance in the plasma proteome

Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care (Palmqvist et al. 2024)

o An example of the potential power of blood plasma as a source of biomarkers

Plasma Proteome Project

Protein Function 201 with Kathryn Lilley

Thu, 17 Oct 2024 08:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 function
Factors that give rise to the dynamic complexity of protein function including proteoforms, protein localization, and moonlighting
Steps we can take to better understand and teach others about the complexities of protein function

Research diving into the complexities of protein function

Research 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 resources

MoonProt - A database for moonlight proteins from Professor Constance Jeffrey's Lab
Translating Proteomics Episode 5 - Why the Biology Surrounding Biology's Central Dogma is Wrong

Are Proteins A Myth? With Special Guest Professor Neil Kelleher

Wed, 02 Oct 2024 17:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 are
Examples of the importance of proteoforms
The scale of and technological advances needed to meet the challenges of proteoform biology.

Some examples of the power of proteoforms covered in this episode

Recent 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 resources

Expanding the Druggable Universe with Proteomics

Wed, 26 Jun 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 proteomics

08:16 - Advancing personalized medicine through proteomics

10:58 - How proteomics technologies have changed drug development

15:13 - New abilities next-generation proteomics technologies give us in drug development

Learn about proteomics and biomarker discovery:

https://youtu.be/8rcAxHSRGYs?si=kZ0UX42TJ8tWIaSN

Learn more about proteomics and precision medicine:

https://youtu.be/bzRlM45agBY?si=eop2XcGLc_oLeiVc

Harnessing Proteoforms to Understand Life's Complexity

Wed, 19 Jun 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 proteoforms

09:38 - Evidence that proteoforms are important and how we can use proteoform data

19:28 - Technology advances needed to understand proteoform biology

The Future of AI in Biomedicine

Wed, 05 Jun 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 biomedicine
05:28 – Difficulties and potential solutions when applying AI to biology
14:20 – How AI will impact the study of proteins
19:34 – Risks of AI in biomedicine

Why the Dogma around Biology's Central Dogma Is Wrong

Wed, 22 May 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 biology

11:58 – The need for new models in biology

Single-protein Biomarkers Don't Cut It

Wed, 08 May 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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.

Some key points of discussion:

Biomarkers are difficult to find because of the methods we use to find them and because there is a ton of variability in natural biological systems
Most proteins are biomarkers
We need more proteome-scale data over space and time to find new biomarkers

Learn more about biomarkers.

Let us know what you think about the podcast.

Biology in Space and Time

Wed, 24 Apr 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 systems

04:45 - How current experimental designs rarely take space and time into account

11:54 - The tools necessary to sufficiently measure biology in space and time

Some key takeaways from the conversation:

Different biological processes occur at very different time scales
Complex, multiomic interactions can only be understood over time and space
We need to properly collect, annotate, and share omics-level data in order to understand the rules that govern complex biology

Let us know what you think about the podcast.

Putting Proteomics to Work

Tue, 02 Apr 2024 09:15:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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.

Let us know what you think about the podcast.

Learn more about applications of proteomics

In this episode, Parag mentions work from Matthias Selbach's Lab. Learn more about the Selbach Lab here.

Poised for a Proteomics Breakthrough

Tue, 02 Apr 2024 09:00:00 -0800

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

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 reality
Why past efforts to broadly leverage proteomics did not work out
What we've learned from the past
What's changed in proteomics and science in general that makes a proteomics breakthrough possible

Learn more about proteomics

Let us know what you think about the podcast.