Andrew Leduc

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.

Also the cells are sorted by growth rate so idk some meaning to the ordering

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

Yeah its not great, it just made comparisons of the different modalities a bit easier to visualize than when we plotted a scatter but will revisit. Thanks for feedback!

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!

I have admittedly been on the non-PI side of this only to realize how true this must be after receiving a blank stare 😅

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...

🧵

Trust me, its better than whatever harm "doing their jobs" will cause...

What about predictions that involve many proteins interacting together?

Yeah, for sure not true but also probably looking under the lamp post effect as well!

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

Once you have a certain level of aggregation, it does become hard to imagine removing it easily. What if the aggregate is too large to fit in a lysosome? I dont know I guess what the size scales are

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.

What do you use to measure blood sugar?

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.

YouTube video by Nikolai Slavov Quantification of gene expression control in a mammalian tissue at single cell resolution | SCP2025

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?...

All ideas != create equal 😅

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

Congrats! You should check out transfer learning workflows applied to RT calibration in alphaDIA from Wallmann et al. Worth a citation I think.

If the idea has obvious significance utility over existing tools, its much more likely to be implemented well at some point in some form

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

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