Parallel Squared Technology Institute (PTI)

Appreciating the unknown helps us discover it. Great oceans of truth lay all undiscovered by modern science. One of them is them is the proteome: nikolai.slavovlab.net/Proteome-secre…

A deeper dive into the article we published last week in @Nature. I will start with the framing and methodology as they are key to understanding the surprising results: Proteomics experiments usually begin with an assumption. nature.com/articles/s4158… 1/

As usually, the Single-Cell Proteomics Conference aims to maximize accessibility.

#SCP2026 will enable virtual attendance via Zoom. It's free but requires registration at single-cell.net Only presentations by speakers who consent to Zoom broadcast will be included in the virtual program.

🔗 Links: Nature Article: nature.com/articles/s4158… OA version: biorxiv.org/content/10.110… Science highlight: science.org/content/blog-p…

The findings reveal a layer of proteome diversity that is largely invisible to DNA and RNA sequences alone. Our knowledge of the proteome remains relatively limited:  It is the next big Scientific Frontier nikolai.slavovlab.net/Proteome-secre… and Parallel Squared Technology Institute (@ParallelSqTech) is building tools to explore it.

Since the 1960s, the genetic code has been used to predict protein sequences from DNA and mRNA sequences.  Our @Nature article demonstrates that these predictions miss thousands of protein sequences present in human tissues. Across >1,000 human samples, we identified numerous abundant proteins whose amino acid sequences differ from those predicted by the genetic code. These proteins are not rare translation byproducts. They accumulate to thousands of copies per cell. Some are more abundant than the proteins predicted by the genetic code from the same transcripts. Their abundance reflects a combination of alternate RNA decoding mechanisms — including codon-anticodon mismatches, tRNA abundance, and RNA modifications — and selective stabilization of the resulting proteins. The last factor – protein stability – emerges as a major determinant of protein abundance across proteins, proteoforms and cell types: #Proteostasis" target="_blank" rel="nofollow noopener">slavovlab.net/research.htm#P… Alternate RNA decoding is pervasive across functional groups of proteins, healthy and diseased tissues. It affects proteins playing key roles in neurodegeneration, and some alternately decoded proteins show strong enrichment in tumors compared to their surrounding tissues. This discovery has been a long and exhilarating journey with Shira Tsour and the @slavovLab team. It started in 2019 and proceeded through many challenges and thrilling highs. A journey that has opened new perspectives that we long to explore! 1/

Go Nikolai!

What are the biggest opportunities in biology today? Understanding the proteome is a huge one. It motivated us to launch @ParallelSqTech: > To increase the sensitivity, scale and resolution for exploring one of biology's most exciting frontiers: youtu.be/9Gz6km1J9Wo?si…

Boston is an amazing city for science, but it's an expensive place to visit. To help make SCP2026 more affordable and accessible, we've secured conference housing for $115 / night. We hope this enables broader participation from students, trainees, and researchers around the world.

The program for #SCP2026 is online. The talks span diverse technologies and biological questions. Join the discussions, flash talks, and hands-on workshop. 🗓️ July 14-16, 2026 | Boston, USA 🔗 Check out the full program: single-cell.net/proteomics/scp…

I feel deeply honored by this recognition of research from @slavovLab, @ParallelSqTech and many collaborators and colleagues. It is very fitting to celebrate the advances in this field with the community that has contributed the most to developing these methodologies. This is recognition of just the first steps of an amazingly promising research endeavor poised to widen, deepen, and reshape our scientific understanding.

Mass spectrometry proteomics loves benchmarks. But I have not seen an important one: - Accuracy of proteome quantification when using short LC gradients. timsTOF and Orbitrap Astral instruments allow quantifying 7 - 9k proteins from 200ng samples using very short short separation times affording the analysis of 200 – 500 samples / day. ⬛ Have you seen accuracy benchmarks for this workflow ?

The annual meeting of the American Society For Mass Spectrometry (@asmsnews) has been very special for me as the Biemann Medal recognized our contributions to developing single-cell proteomic technologies and using them to open new perspectives through which we can discover and understand biological phenomena. The journey is made more wonderful by sharing it with a collaborative and thoughtful community. I am deeply grateful to all who have contributed to the research recognized by the Biemann medal, a very special distinction and recognition for research that is gaining momentum.

Single-cell proteomics illuminated new mechanisms of mammalian development. We found that spatially polarized protein distributions and intracellular protein gradients emerge during the earliest stages of mammalian embryogenesis and help bias subsequent cell fate decisions. Critically, these developmental mechanisms are not reflected in mRNA abundance: the key biology resides in the spatial organization, abundance, and asymmetric localization of proteins within and between cells. The results show that early developmental patterning is associated with polarized localization of specific proteins and coordinated proteomic asymmetries across blastomeres, linking protein organization directly to lineage specification. These findings support a model in which cell fate in the mammalian embryo is not determined solely by stochastic transcriptional programs, but is strongly shaped by inherited and dynamically regulated protein states that establish developmental competence before overt differentiation: cell.com/cell/fulltext/… Our results depended critically on single-cell proteomics analysis, on direct measurement of the molecular effectors that execute developmental decisions — capturing gradients, localization, stoichiometry, and post-transcriptional regulation. The future of developmental biology will depend increasingly on quantitative single-cell protein measurements capable of resolving the molecular architecture of cell fate determination: doi.org/10.1242/dev.20…

The final version of our @AnnualReviews article is now published OA: annualreviews.org/content/journa…

These numbers are key to understanding RNA and protein analysis. The different counting statistics fundamentally shape technological challenges and opportunities. nature.com/articles/s4159…

Congratulations to Nikolai Slavov, recipient of the 2026 ASMS Biemann Medal! This award recognizes significant early-career achievement and highlights emerging leaders shaping the future of #massspectrometry. #TeamMassSpec

Intrinsically disordered regions do not lack structure: Rather, they encode structural plasticity. This plasticity is not a limitation of biology, but one of its most powerful design principles. This research frontier inspires our team at Parallel Squared Technology Institute (@ParallelSqTech) to develop experimental and computational approaches to measure, model and understand the ensembles of protein conformations that underpin biological functions.

Next Monday (May 11), I will be in Madrid to share our research. I will present results from @ParallelSqTech and @slavovLab, including our latest proteomic technologies and the biological questions they are answering.