Naveen C

inter alia

[Naveen C @naveennav25]

Away from the jamboree, cocooned in my own small world of dreams and slight disruptions

[Biology+AI Daily @BiologyAIDaily]

Traiblazer: generative multicellular perturbation model of biology

1. TRAILBLAZER introduces a transformer‑based encoder that treats each patient sample as an unordered set of single‑cell profiles, using a small number of learned latent tokens to aggregate and redistribute global context while maintaining near‑linear computational scaling.

2. The model couples this encoder to a hyperspherical latent space that is explicitly shaped by a frozen library of mechanism directions derived from a separate segmentation network. Healthy states are pulled toward the center and perturbations lie on the unit sphere, allowing biologically meaningful vector arithmetic.

3. By aligning perturbation vectors with these calibrated directions, TRAILBLAZER can compose and extrapolate intervention effects, achieving accurate zero‑shot predictions for unseen treatments such as IL‑15, IL‑10, and IFN‑γ, and ranking immunomodulators with a rediscovery rank that improves from random to top‑5 after latent shaping.

4. Compared to state‑of‑the‑art single‑cell and multicellular baselines (CellFlow, STACK, LPM), TRAILBLAZER consistently delivers lower reconstruction error, higher fidelity in gene‑expression distributional matches, and stronger generalization to new donors, laboratories, and perturbations.

5. In a virtual breast‑cancer trial, the model simulates counterfactual post‑PD‑1 treatment states for naive patients, feeds them into a multicellular responder classifier, and reproduces clinical response probabilities with an ROC AUC of ~0.93, outperforming baseline classifiers that lack virtual simulation.

6. The latent arithmetic framework also enables patient‑specific ranking of combination therapies: by projecting the required shift toward a responder phenotype onto the mechanism library, TRAILBLAZER identifies synergistic partners (e.g., IL‑15, IFN‑γ) that are corroborated by literature, while providing per‑cell importance maps that highlight which immune populations drive predicted outcomes.

7. The authors acknowledge trade‑offs such as a modest increase in reconstruction error after latent shaping and the current reliance on harmonized gene sets; future work will extend the decoder to multimodal data, incorporate dosage and scheduling, and explore cross‑species alignment to support preclinical translation.

8. Overall, TRAILBLAZER offers a practical framework for mechanistically informed simulation of multicellular responses, paving the way for predictive foundation models that can guide therapeutic discovery and virtual clinical trial design.

📜Paper: https://t.co/ltrKdlbCbx
#ComputationalBiology #SingleCell #AIinMedicine #VirtualTrials #MulticellularModel #DrugDiscovery #PrecisionMedicine

[Naval @naval]

If you aren’t getting happier as you get older, you’re doing it wrong.

[Naveen C @naveennav25]

@sanjeevsanyal You cannot use it as a bargaining chip if you stop asking. But agree should not lose leverage over that issue.

[Naveen C @naveennav25]

@pranamanam @rohitsingh8080 Wow

[scott belsky @scottbelsky]

“When you're playing a point, it has to be the most important thing in the world. And it is. But when it's behind you, it's behind you.” - @rogerfederer

[Reads with Ravi @readswithravi]

“I am a slow walker, but I never walk back.”

— Abraham Lincoln

[Naveen C @naveennav25]

@mairal @parakala A husband who turned vile and bitter with every passing success of his wife. Unfortunate.

[Sahil Bloom @SahilBloom]

Andy Weir's short story, The Egg, is one of the most mind-blowing things you will ever read.

Do yourself a favor and find 10 minutes to enjoy it.

(bookmark this for later)

[Naveen C @naveennav25]

@svaradarajan I feel sad for the people who suffer on the ground because people of your ilk hijack their cause to fuel your own ulterior motives and political objectives.

[Naveen C @naveennav25]

India voted in favor of an amendment that would have also condemned the terror attacks on Israel while calling for a ceasefire in Gaza. If you were fair and sensible, you would appreciate that nuance and criticize those who defeated that amendment and a larger consensus for a ceasefire. Instead, you use this to diss India. 👏👏👏

[Trey Yingst @TreyYingst]

Imagine the worst things possible that can be done to humans.

Hamas did all of that and more to Israeli civilians. Babies beheaded. People burned alive in their homes. Women raped and dragged through the streets.

Don’t look away.

[Naveen C @naveennav25]

@sachin_rt Mainstreaming and encouraging the idea of photographing these animals in the wild may not be wise. Let them be. The last thing we need is more humans in Indian forests with noisy camera clicks.

[Naveen C @naveennav25]

Here I am stuck with a blue tick as I tried to pay my way out of #RateLimitExceeded

[Phillip Compeau @PhillipCompeau]

This is the best video to introduce a computational biology course. There will never be a better one

https://t.co/K59A2iQWFU

[Bo Jacobsson @BoJacobsson]

Genetic conflict with the fetus determines when women give birth

Nineteen years of collaborative work.

https://t.co/0GI0i2OQ9y

[Naveen C @naveennav25]

@drkohilathas Prof. Colin Campbell, formerly at Cornell, interestingly has a similar take on reductionist vs ‘wholistic’ approaches to understanding human health

[Naveen C @naveennav25]

@nealkhosla What an underrated tweet this is! The tendency to over optimise in various transactions, business or otherwise, is high among elite young adults as a result of lacking that normal adult experience.

[Likai Tan 谭力凯 @likai_tan]

Totally shocked. #GPT-4

[Naveen C @naveennav25]

See that a lot

[Cory Doctorow NO LONGER ON TWIT TER @doctorow]

Doug @Rushkoff says that the ethic of today's "entrepreneur" is to #GoMeta - don't provide a product or a service, simply find a way to be a predatory squatter on a chokepoint between people who do useful things and people who use those things.

[Science girl @sciencegirl]

Emergency workers rescuing a dog from under rubble in Iskenderun, Turkey