@biorxivpreprint.bsky.social Scalable transcription factor mapping uncovers the regulatory dynamics of natural and synthetic transcription factors in human T cell states
www.biorxiv.org/content/10.1...

🚨 new glioblastoma preprint alert!

we present the first spatially resolved single cell atlas comparing radionecrotic changes (RN) and recurrent IDH-wildtype glioblastoma (GB) –– shedding light on a long-standing diagnostic challenge.

🧵 1/

How many papers are truly irreproducible and how many show a possible causal path which often isn’t the limiting factor and is conditional on important context (eg mutations, genetics, environment of the experiment)?

Thinking about omnigenic model, “mechanistic bias” in medicine, personalised PRS.

Hepatic acetyl-CoA metabolism modulates neuroinflammation and depression susceptibility via acetate @cp-cellmetabolism.bsky.social
www.cell.com/cell-metabol...

Congratulations on getting this out🎉!

It is really cool that it seems to be possible to learn important non-coding variation from cell type agnostic data - ei can you find sequences that are CREs/enhancers at least is some cell type in the body without collecting the data from all cell types?

Very impressive work and interesting modelling ideas 💡:

By training GPN-Star on vertebrate, mammal, and primate alignments, we reveal task-dependent advantages of modeling deeper versus more recent evolution. These findings offer new biological insights and practical guidance for developing future gLMs and evolutionary models.
(6/n)

This is truly an incredible breakthrough IMO. Really exemplifies what you get when deep domain expertise (popgen/evolution/disease genetics in this case) fuses with cleverly crafted ML. What u get r sleek, well thought out architectures that absolutely destroy the behemoths. Wow!! 1/

Ideally of course - like work laptop, email and slack - the noise cancelling headphones 🎧 will be a part of the starter package 📦.

£40 for earplugs sounds ridiculous but they are infinitely reusable and very comfortable.

£200-300 for headphones sounds pretty expensive but lost energy, effort and productivity is ultimately much more expensive.

If you start your PhD next month get both ASAP in the first 1-3 months.

I also recommend loop earplugs especially for sleep but they are less functional for work because you can still hear people through them - whereas noise cancelling headphones music can pretty much mute everything else.

If you feel like you need noise canceling headphones 🎧 - you probably actually need to buy them right now. Don’t delay this decision and loose time trying to operate without them.

Noise cancelling headphones are like your work email+slack - you may be able to work without them but it’s pretty hard.

Has anyone ever seen a house/flat in the UK/Cambridge that had an HRV or ERV system?

If you can’t have windows open at night due to security concerns how are you supposed to ventilate?

I tried closing windows and even with the fan on max CO2 levels never got below 850ppm (bad for sleep quality).

With unprecedented 38× coverage, our atlas resolves single neuron clusters and shows that separate waves of neurogenesis use different modes of molecular identity encoding: discrete in early born and continuous in late born. 3/8

Neuronal diversity is written in transcriptional codes 🧬. But what is the logic of these codes that define cell types and wiring patterns?
To find out we built a #scRNAseq developmental atlas of the Drosophila nerve cord and linked it to the #connectome 🪰🧠
#preprint thread ⬇️1/8

Soft equating the two tasks leads to a number of problems

* overestimated complexity of perturbation prediction problem
* overlooking other tasks needed for reversing disease state
* overoptimistic assessment of success for reversing disease state based on success of perturbation prediction
…

And he made it again!...tour the force from JIa-Wei´s Wang lab using comparative sc-transcriptomes, and developing new analytical tools, to tackle evolutionary trajectories of plant cell types!. Amazing work as usual! www.cell.com/cell/abstrac...

That task requires substantial additional input into the models and deeper considerations of assumptions (eg whether mechanisms used to drive change are reversible) than a more narrowly specified task of perturbation prediction.

An example of using biological terms at a wrong level of abstraction is perturbation prediction where a paper by @const-ae.bsky.social recently showed that DL doesn’t outperform linear baselines. The real task is predicting how to reverse disease associated decisions to switch on/off specific genes.

Ended up coming back to these points to articulate state of the GRN field in the paper/fellowship introduction. Introductions need to be specific about the task specification and model-task mismatch in existing work. Task specification need to match biology terms at the right level of abstraction.

👀 we are involved in projects 1 & 6 on the list:

1️⃣ Multicellular molecular characterisation of inflammatory bowel disease
6️⃣ Designing Efficient Single-Cell Perturbation Experiments with Lab-in-the-Loop AI Agents

📅 Application deadline is 30th September ❗

Welcome @timcoorens.bsky.social ‪ ‬🇳🇱, our new Research Group Leader.

Find out how Tim’s group is exploring using large-scale single-cell and spatial data to trace cell lineages, understand cancer origins, and uncover how mutations drive disease.

www.ebi.ac.uk/about/news/p...
🖥️🧬

Just saw this talk yesterday youtu.be/fHWFF_pnqDk?...

Looks like it’s exactly what they recommend - only use it when you can verify easily and also in parts of the codebase that are not likely to be used elsewhere. My interpretation - fine for results visualisation plots but not model code.

Posting what you think about political issues on these public platforms is not a good idea. Too much risk. Maybe it’s fine for some people but not for everyone.

So you see 10-20% of science and can only say extremely general things about politics. Not very productive use of time 🕰️.