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We report many proteins not predicted by the genetic code.

They are stable & abundant O( 10³ ) copies / cell.

Generative mechanisms include codon-anticodon mismatches & RNA modifications.

Their abundance depends on codon frequency & protein stability.

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Biology advances in leaps, and the leaps follow measurement. Sequencing DNA gave us genomes and transcriptomes.

The next leap will come from embracing the molecules and processes animating life.

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Replying to @slavov_n
In pursuit of this new direction, our team at @ParallelSqTech developed multiple timePlex implementations.

They demonstrate strong potential. A few highlights include:
biorxiv.org/content/10.110…

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A major update on combinatorial scaling of proteomics throughput using time-encoded multiplexing.

Mass spec proteomics has long multiplexed samples in the mass domain (with mass tags). timePlex multiplexes in the time domain, setting a direction with new possibilities.

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Participating in the rapid evolution of this technology, from proof of principle to a robust, quantitative methodology, has been a thrilling adventure.

Writing this perspective revived many wonderful memories and brought a bright smile to my face.
New ACS Editors' Choice from @J_ASMS!

Congratulations to Nikolai Slavov! His Perspective explores a decade of advances in single-cell proteomics and the new possibilities they're opening for biology.

Read more: doi.org/10.1021/jasms.…

#JASMS #TeamMassSpec #MassSpectrometry
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Realizing this workflow for single-cell proteomics benefited from discussions at the 2025 single-cell proteomics conference.

Facilitating such collaborations is a core part of @SCP_meeting's mission !
Parallel Squared Technology Institute aims to scale the throughput of sensitive proteomics without compromising quantitative accuracy, depth or specificity.

Today, we share a step in this direction:
🔹 A workflow supporting the analysis of 1,130 single-cell samples per day depth and quantitative accuracy.

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Slavov Laboratory retweeted
Parallel Squared Technology Institute aims to scale the throughput of sensitive proteomics without compromising quantitative accuracy, depth or specificity.

Today, we share a step in this direction:
🔹 A workflow supporting the analysis of 1,130 single-cell samples per day depth and quantitative accuracy.

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Protein functions depend on the full amino acid sequence, including isoforms, cleavage products, and modified residues that distinguish proteoform states.

To capture these modifications, we and @ParallelSqTech introduce multiDIA to increases proteome sequence coverage.
Proteomics has long faced a choice: Go deep, or go fast.

Deep, high-confidence coverage of protein sequences has traditionally required extensive chromatographic fractionation, large sample inputs and data acquisition times too long to be practical for analyzing human cohort data-independent acquisition (DIA) workflows handle many samples quickly, but detect less of each protein and with lower confidence.

Our new preprint introduces multiDIA: It gets more from each sample without fractionation.

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Proteomics has long faced a choice: Go deep, or go fast.

Deep, high-confidence coverage of protein sequences has traditionally required extensive chromatographic fractionation, large sample inputs and data acquisition times too long to be practical for analyzing human cohort data-independent acquisition (DIA) workflows handle many samples quickly, but detect less of each protein and with lower confidence.

Our new preprint introduces multiDIA: It gets more from each sample without fractionation.

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Congratulations to Luke Khoury on the successful defense of his dissertation.

Working, learning and growing together has been fun.
I am proud of his scientific growth.

Our research has opened a fresh perspective on peripheral immune cells:

doi.org/10.64898/2026.…
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The regulatory variation within a cell type is remarkably informative and interesting.
This gets particularly interesting in single cells from the same cell type.

Working at the cell type level misses much of the action.

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Replying to @slavov_n
This gets particularly interesting in single cells from the same cell type.

Working at the cell type level misses much of the action.

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Join the Dissertation Defense of Luke Khoury:

Decoding Cell-Type-Specific Functional Coordination in Primary Human Immune Cells

Thursday, October 15, 2026 | 9:30am-11:30am EST
Richards Hall 229
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Join the Dissertation Defense of Luke Khoury:

Decoding Cell-Type-Specific Functional Coordination in Primary Human Immune Cells

Thursday, October 15, 2026 | 9:30am-11:30am EST

Richards Hall 229
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Slavov Laboratory retweeted
Do you need an intro to analyzing (prote)omics data?

This series of lectures may be helpful.
We aimed to make them short & accessible.

Enjoy watching & learning !

youtube.com/playlist?list=…
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Read the methods before reading the results
Read the methods before reading the conclusions
Read the methods before evaluating the conclusions
Read the methods before making conclusions

Read the methods!
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A video summary of our recent preprint

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How much data would it take to describe human biology ?

A very crude description of molecular abundance requires 1,000× more bites than all digital data humanity stores.

We need more than scale to close the gap.

blog.slavovlab.net/2026/09/27/how…
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Using single-cell proteomics, we discovered protein (and functional) symmetry breaking in early mammalian embryos influencing cell fates.

These proteomic asymmetries are detectable at the zygote stage, intensify by the 2-cell and 4-cell stage, and correlate with the sperm entry lization as a symmetry-breaking event. The clear protein differences allowed us to define two types of blastomeres, termed alpha and beta.
⬛ These differences predict the developmental potential of the blastomeres. Similar clustering and protein enrichment patterns found in human 2-cell embryos suggest this early asymmetry might be conserved.

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Beyond heterogeneity, single-cell analysis can reveal functional coherence.

Coherence, regularity and principles advance science.

Full recording: youtube.com/watch?v=z0dIhG…
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Millions of PBMCs have been analyzed by scRNA-seq. Have we seen it all ?

We profiled thousands of single PBMCs — proteomes and transcriptomes side by side — and uncovered functional coordination undetectable in the deepest scRNA-seq we could perform.

biorxiv.org/content/10.648…

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