Nikolai Slavov

Mapping cryptic phosphorylation sites in the human proteome | The EMBO Journal imageimageThe study reports a class of phosphorylation sites, named cryptic phosphosites, buried within protein cores. Their transient exposure during folding suggests a novel regulatory mechanism lin...

Mapping cryptic phosphorylation sites in the human proteome

www.embopress.org/doi/full/10....

Nascent proteins may be phosphorylated during translation & the phosphosite buried in the protein’s inner core

Such buried phosphosite are found in ~ 1/3 of the phosphorylated human proteins.

They can influence protein abundance (👇), providing another example for proteoform specific regulation.

Protein degradation plays major roles in aging physiology & pathology.

We can start analyzing it quantitatively at higher resolution & scale.

A promising new direction for aging research 🚀

@slavov-n.bsky.social and @anshulkundaje.bsky.social on current trends of escalating hype in #AntiScience

... the changes in protein abundance.

These changes in protein abundance and clearance are functionally coordinated and affect multiple pathways, including proteasomes, spliceosomes, and chromatin regulators.

Aging is associated with changes in protein abundance in many organs and tissues.

We find that the protein changes are cell-type specific, and thus muted in previous bulk analysis.

Protein clearance rates change with age and drive the ...

www.biorxiv.org/content/10.1...

Valor Very few human acts are more inspiring than courage and defiance in the face of insuperable evil. While such defiance and courage might appear foolish and futile, they may be decisive for beating e…

I reread an old blog post that seems current.

Let's have courage to defend what is right even against overwhelming might.

blog.slavovlab.net/2015/06/15/v...

The human inactive X chromosome modulates expression of the active X chromosome Through RNA sequencing of individuals with sex chromosome aneuploidy, San Roman et al. identify modular “active” (Xa) and “inactive” (Xi) X chromosome transcriptomes. Looking beyond classical X inacti...

The human inactive X chromosome modulates expression of the active X chromosome

www.cell.com/cell-genomic...

Quantitative assessment of Xi contributions to X chromosome gene expression.

The ‘‘inactive’’ X chromosome (Xi) is active.

Xi regulates gene expression from the active X.

1/n

Mechanotransduction in the nucleus

Multiple TFs transmit mechanical forces into transcriptional regulation.

Nuclear shape, size, and chromatin abnormalities are common features of many diseases.

Protein restriction reprograms the multi-organ proteomic landscape of mouse aging Comprehensive proteomic analysis of 41 mouse tissues reveals tissue-specific aging hallmarks and demonstrates that dietary protein restriction mitigates age-related molecular changes, improves adipose...

Clearly, protein regulation is central to aging:

Protein restriction reprograms the multi-organ proteomic landscape of mouse aging

www.cell.com/cell/abstrac...

Principles of protein abundance regulation across single cells in a mammalian tissue Protein synthesis and clearance are major regulatory steps of gene expression, but their in vivo regulatory roles across the cells comprising complex tissues remains unexplored. Here, we systematicall...

The authors report that protein restriction mitigated aging associated changes in protein abundance and improved adipose tissue functions.

This makes it very curious about its impact on protein synthesis and degradation rates. What are the regulatory mechanism ? doi.org/10.1101/2025...

High-protein diets are in vogue, often based on dubious quality supplements.

Yet, low-protein diets appear to have aging benefits.

Those are the subject of this new article in Cell:

Protein restriction reprograms the multi-organ proteomic landscape of mouse aging

The antibodies don’t work! The race to rid labs of molecules that ruin experiments Poorly performing antibodies have plagued biomedical sciences for decades. Several fresh initiatives hope to change this.

The antibodies don’t work! The race to rid labs of molecules that ruin experiments

Poorly performing antibodies have plagued biomedical sciences for decades. Several fresh initiatives hope to change this.

www.nature.com/articles/d41...

Many articles reported using an antibody ... that didn’t even bind the key protein in Laflamme’s testing. Those articles had been cited over 3,000 times.

A key question is:

◼️ 𝐂𝐚𝐧 𝐩𝐫𝐨𝐭𝐞𝐢𝐧 𝐛𝐢𝐧𝐝𝐞𝐫𝐬 𝐚𝐜𝐡𝐢𝐞𝐯𝐞 𝐡𝐢𝐠𝐡 𝐬𝐩𝐞𝐜𝐢𝐟𝐢𝐜𝐢𝐭𝐲 𝐟𝐨𝐫 𝐞𝐯𝐞𝐫𝐲 𝐞𝐩𝐢𝐭𝐨𝐩𝐞 & 𝐩𝐫𝐨𝐭𝐞𝐨𝐟𝐨𝐫𝐦?

Some investors assume an answer.

Largest study of its kind shows AI assistants misrepresent news content 45% of the time – regardless of language or territory An intensive international study was coordinated by the European Broadcasting Union (EBU) and led by the BBC

AI assistants misrepresent news content 45% of the time

- 45% of all AI answers had at least one significant issue.

- 31% of responses showed serious sourcing problems

- 20% contained major accuracy issues

www.bbc.co.uk/mediacentre/...

Very concerning.

New research coordinated by the European Broadcasting Union (EBU) and led by the BBC has found that AI assistants – already a daily information gateway for millions of people – routinely misrepresent news content no matter which language, territory, or AI platform is tested.

ADTnorm: robust integration of single-cell protein measurement across CITE-seq datasets - Nature Communications Here the authors present a computational method that expands the potential of multimodal single-cell analyses by delivering an accurate, fast, and user-friendly approach for normalizing and comparing ...

Source:

ADTnorm: robust integration of single-cell protein measurement across CITE-seq datasets

www.nature.com/articles/s41...

How quantitative are protein abundance estimates based on affinity reagents ?

These distributions of T cell lineage markers (CD3, CD4) were estimated by CITE-seq.

They benefit from using some of the best antibodies available.

Yet, they are highly variable across batches.

...

1. Communication silos and intellectual barriers.

2. Low accessibility of the tools, especially for scalable commercial enterprises.

My recent meetings with pharma leadership were united by a resonant theme:

- "𝑀𝑦 𝑡𝑎𝑟𝑔𝑒𝑡𝑠 𝑎𝑟𝑒 𝑝𝑟𝑜𝑡𝑒𝑖𝑛𝑠, 𝑎𝑛𝑑 𝐼 𝑛𝑒𝑒𝑑 𝑡𝑜 𝑚𝑒𝑎𝑠𝑢𝑟𝑒 𝑡ℎ𝑒𝑚 𝑑𝑖𝑟𝑒𝑐𝑡𝑙𝑦"

Remarkably, very smart colleagues were unaware of the tools that can support their objectives.

This is due to ...

The Science Sanz Hub did a podcast highlighting our recent preprint.

www.youtube.com/watch?v=LZTX...

When Variant Proteins Aren't Actually the Variant Ones

When the weirdo variant protein versions outnumber the “real” ones:

YouTube video by Nikolai Slavov Proteomics: The arc of progress in life sciences | Research Fest by PTI

The big picture:

Tracing the arc of conceptual milestones in life sciences over the past century, centered around major discoveries driven by evolving technologies.

We are excited about the progress & the research enabled by tech from @ParallelSqTech.

youtu.be/SrzoLGBVTsY?...

In silico biological discovery with large perturbation models - Nature Computational Science A large perturbation model that integrates diverse laboratory experiments is presented to predict biological responses to chemical or genetic perturbations and support various biological discovery tas...

In silico biological discovery with large perturbation models

www.nature.com/articles/s43...

Deep-learning integrates heterogeneous perturbation experiments, models the context, and achieves good predictions.

I like the name:
- large perturbation model (LPM)

It describes the model without unrealistic overstatements.

A thoughtful highlight of our results on alternate RNA decoding:

Highlight: www.science.org/content/blog...

Preprint: www.biorxiv.org/content/10.1...

Mechanical confinement can trigger cancer invasion.

Mechanical forces regulate the switching of melanoma cell behavior between proliferation and invasion.

This community is building foundational capabilities for technological progress.

Its nonprofit initiatives allow broadly sharing these capabilities.

I am happy to support this mission 🚀