Next week, @andrewleduc.bsky.social will present at the CSHL Systems Biology: Global Regulation of Gene Expression meeting. His talk will focus on in vivo protein regulation in single cells, including results from this preprint: www.biorxiv.org/content/10.1...

These 3-L bottles contain one million tiny colored spheres each. One sphere is black (1 ppm). Finding the black sphere is comparable to detecting a protein present at ~ 6,000 copies in the proteome of a human cell. Quantifying the protein requires analyzing multiple jars.

When designing antibodies for cell surface proteins, how much do the PTMs (glycosilation specifically) affect how well proteins can bind. Presumably these things are not possible to model with current approaches so I am surprised they apparently work so well

Check out our recent work interpreting the contribution of transcription, translation, and protein clearance on regulating protein abundance across cell types and single cells from a mammalian tissue!

Some proteins are primarily regulated by one mechanism: RNA abundance, translation, or clearance. The regulation of most proteins is dominated by different regulatory mechanisms across cell types. Gratifyingly, this complex regulation defines simple rules ⬇️ www.biorxiv.org/content/10.1...

We quantified mRNA abundance, translation, protein abundance, protein degradation and cell growth across thousands of single cells from a mammalian tissue. The results revealed 𝐜𝐨𝐦𝐩𝐥𝐞𝐱 regulation & 𝐬𝐢𝐦𝐩𝐥𝐞 organizing principles: www.biorxiv.org/content/10.1... 🧵

What is the best way to compute the correlation of two transcripts across single cells?

Help me build a virtual version of my apartment by training a hugeee (like so huge) neural network on temperature data from my stove. Call to action from the community to achive this ambitious goal!

* Transcript abundance predictor model

Is it well appreciated that droplet mRNA seq methods massively under-captures nuclear encoded mitochondrial transcripts? They are essentially entirely unquantified by 10x sample preparation, probably because cell lysis is not sufficiently strong.

Anyone out there working on single cell ribo seq, this is potentially an interesting alternative/complementary approach. There are some differences in the information they give and would be interesting to explore.

The aspiration to directly measure the 𝐫𝐚𝐭𝐞𝐬 of protein synthesis and degradation and control mechanisms of gene expression in the individual cells comprising mammalian tissues has always been a significant motivating factor for me to develop single-cell proteomic technologies. 1/n

How do different cell types regulate protein concentrations? Transcription is only part of the story! Our project focuses on better understanding the regulation of protein abundance by measuring transcription, translation, and protein clearance in single cells.

The talk by @andrewleduc.bsky.social at #SCP2025 is on YouTube: 𝐐𝐮𝐚𝐧𝐭𝐢𝐟𝐢𝐜𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐠𝐞𝐧𝐞 𝐞𝐱𝐩𝐫𝐞𝐬𝐬𝐢𝐨𝐧 𝐜𝐨𝐧𝐭𝐫𝐨𝐥 𝐢𝐧 𝐚 𝐦𝐚𝐦𝐦𝐚𝐥𝐢𝐚𝐧 𝐭𝐢𝐬𝐬𝐮𝐞 𝐚𝐭 𝐬𝐢𝐧𝐠𝐥𝐞 𝐜𝐞𝐥𝐥 𝐫𝐞𝐬𝐨𝐥𝐮𝐭𝐢𝐨𝐧 youtu.be/adkY6txDyqs?...

You ever just flip through genes for a while reading the functions on uniprot and just think, Wow cells do so much stuff

Yes, testis are special but not the only tissues in which we see substantial discrepancies. We have seen them in all tissues that we have analyzed, and @andrewleduc.bsky.social has even more compelling examples from mouse trachea ... soon to be published!

must be incredibly frustrating and disheartening to have federal funding that was promised to you for important work suddenly and arbitrarily ripped away

You can't comply your way out of fascism

mitochondrial function, stress response, apoptosis, and autophagy experts, is this right

Congratulations Dr. Rahul Ragunathan on a successful defense @fanglab.org 🎉🎉

More evidence for the role of protein degradation in significantly shaping the proteome of brain tissue!

Julia presented remarkably simple and interpretable models from sophisticated measurements.

Multiplexed single cell proteomics to the moon 🚀 🚀

📊 Using stable isotopes of C/N/O, PSMtags increased protein datapoints from 4,340 (label-free) to 28,359 in the same time. We demonstrate 240 samples per day, but over 1,000 are possible with shorter runs. That’s millions of protein data points per day.

Amazing amount of progress made advancing high throughput proteomics in such a short time from the team at @parallelsq.bsky.social 🚀

We are excited to introduce ‘time’ as a new domain for proteomics multiplexing! It enables: -Label-free multiplexing -Combinatorial multiplexing with plexDIA Using combined 9-plexDIA and 3-timePlex we demonstrate 27-plex DIA 🚀

Read our new paper in Nature Comms: SPIED-DIA = spike-in enhanced DIA phosphoproteomics -> Boosts detection of key phosphosites -> Reveals JNK activation upon MEK inhibition in CRC cells -> Dual MEK/JNK targeting impairs growth 🔗 rdcu.be/enPF2 #proteomics #DIA #cancer

We have projects available on single-cell proteomics, including methods development, and applications to antiviral development and resistance. If you have a strong background in proteomics and are considering an MSCA, get in touch! marie-sklodowska-curie-actions.ec.europa.eu/news/msca-op...

So you’re telling us the radical transparency people are against… transparency? www.politico.com/news/2025/05...

The scientific literature is at risk of becoming flooded with papers that make misleading health claims. www.nature.com/articles/d41...

NEW: Under Trump, the National Science Foundation is awarding grants at the slowest pace in decades. We took a detailed look at every area of science affected by the funding lag. Here's a gift link: www.nytimes.com/interactive/...

When I was starting out modeling data, I always assumed that I needed to learn lots of fancy techniques and read different statistics text books to do useful analysis. However, intuition has gotten me much farther than time spent reading about complicated techniques.

Tune in to hear me give a talk on our work quantifying mechanisms protein abundance regulation in single cells from primary tissues!

This week, PTI will be sharing 4 preprints, including: ⬛️ New tools & mass tags for plexDIA ⬛️ 27-plex DIA enabling 500 samples / day ⬛️ Improved de novo sequencing of peptides ⬛️ Protein degradation dysregulation in Alzheimer's Check out @parallelsq.bsky.social for updates 🚀

You might have guessed where I'm going with this:

 Who is going to do this today? America is giving up its scientists, driving them out with racism, closed-mindedness, and a simple lack of funding, just as Europe did 100 years ago. Who are the random department store owners who will hire them?

Slow growth rates mean stable proteins have time to accumulate inside cells. The resulting consequence is that protein concentrations strongly depend on proteins degradation rates

𝐓𝐨 𝐮𝐧𝐝𝐞𝐫𝐬𝐭𝐚𝐧𝐝 𝐭𝐡𝐞 𝐛𝐫𝐚𝐢𝐧, we need to understand what shapes its molecular composition. What are the contributions of protein synthesis and degradation rates to determining protein abundance in the brain ? www.biorxiv.org/content/10.1...

@bsky.app Why are there no polls??

I just ran a sample that nearly out performed the state of the art in the beginning of my PhD 6 years ago, using 1/4000th the amount of sample in ~1/4th the time. That is pretty amazing.

We think this artifact may be more pronounced in single cell proteomics as compared to transcriptomics as proteins are a considerably smaller than the transcript that encodes them

This project started with an exciting discovery. As @andrewleduc.bsky.social and team interrogated deeper, we found artifactual contributions. So, we developed methods (scp.slavovlab.net/QuantQC) to reduce such artifacts. nature.com/articles/s41... rdcu.be/ekKTq 🧵

Our paper on the impact of protein leakage due to loss of membrane integrity for single cell proteomic sample prep is out in @natcomms.nature.com! We analyze thousands of primary single cells from murine tracheal tissue and record membrane permeability (sytox-green)🧵 www.nature.com/articles/s41...

The most profound insights are often also the most simple: growth-rate, by setting the dilution rate of intra-cellular molecules, controls the sensitivity of gene regulatory circuits. In retrospect it seems crazy that this effect seems to have been overlooked so far. www.science.org/doi/10.1126/...

Great to see confirmed that dilution rates have a major effect on protein concentrations in mammalian cells as well. Crucially, some of these proteins are regulators, and our work specifically investigates how this dilution effect propagates to affect the behavior of gene regulatory circuitry.

Confounders are a major bottleneck to understanding biology. Interactions confounded by unobserved regulators (variables) cannot be causality inferred. Gazillion data points from the observed variables cannot compensate for unmeasured confounders. What can help ... 1/2

We measured degradation rate for over 10,000 proteins from over 115,000 peptide sequences which allowed us to explore how the stability of alternative splicing products affects their abundance. We found a strong overall relationship and visualize a few compelling examples!

www.sciencedirect.com/science/arti... Really fun weekend read! Definitely came a way from it favoring programmed aging.

Congrats! @pierresabatier.bsky.social Finding from figure 7C that long lived proteins have lower abundance in dividing cells is indeed striking! Our paper on dilution due to cell division impacting abundance in a deg rate dependent manner explains this phenomenon. www.biorxiv.org/content/10.1...

In vitro cell lines grow fast and protein abundance variation is explained largely by protein synthesis rate: RNA abundance & translation efficiency In contrast, protein degradation is a major - sometimes dominant - factor in differentiated cells from tissues. Why ? 👇

Analysis by altmetric shows increasing posting of research content on Bluesky but more sharing (reposting) on X. We need to increase Bluesky connectivity and share more.