tuomo kiiskinen • md-phd • building ai-powered next gen biomedicine @Stanford • quant genomics x data sci x comp bio
Palo Alto, CA
Joined September 2022
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The central problem of biology is the origin of biological organization. In our preprint, “Information-theoretic Limits on Programmatic Specification of Biological Systems,” we show, using information theory, that an organism does not contain enough organism-specific information to specify its own fully functioning microscopic organization.
For over 70 years—since the discovery of the double helix and the cracking of the genetic code—biology has been dominated by the metaphor of the genome as an executable computer script or structural blueprint. Yet, it has remained a central mystery how the genome organizes the entirety of the microscopic, fine-scale molecular biological machinery in space and time.
We wish to put forward a radically different formulation.
We show, as an analogy, that the genome is not a figure-skating program choreographing every molecular movement, but a hockey coach’s game plan : roster, tactics, line assignments. The exact trajectory of the puck is computed by physics at runtime. The game looks like hockey because of the specified ensemble, not because every coordinate was pre-programmed.
The organized machinery of life is not the execution of a fully prewritten organism-specific program under favorable conditions. Rather, it is the compilation of a coarse organism-specific specification by a shared physical background that is constitutive of biological organization.
We establish the threshold as a family of maximal capacity-compatible coarse-grainings, distinguish the proven impossibility below the threshold from the empirically realized coarse mappings above it, and locate the threshold empirically through worked cases of protein folding, E. coli, Drosophila early development, and C. elegans, together with computational verification using AlphaFold-2 (analyzing tertiary structures of 555,846 proteins across 46 AlphaFold-2 proteomes), the JCVI-syn3A 4D whole-cell simulation, and canonical stochastic gene network models. We further show that no known naturally realized environmental channel can close the gap. The result rules out programmed microstate determinism while leaving physical determinism untouched, reframes the genome as a generator specification rather than a trajectory program, and unifies gene-centric, developmental, and field-theoretic (bioelectric, morphogenetic, and related continuum) views of biological specification under a single coarse-graining framework.
It has not escaped our notice that this framework has fundamental implications for understanding evolutionary search, heritability, thermodynamic order, biological modeling, and artificial intelligence in biology, but these will be published elsewhere.
biorxiv.org/content/10.64898…
TORILLE 🇫🇮🇫🇮🇫🇮🚀🚀🚀
one of the very few euro “atoms” decacorn startups btw
Today, President of the @EU_Commission Ursula @vonderleyen mentioned ICEYE in her State of the Union address.
ICEYE started with two engineering students, one Finnish and one Polish, who met on an Erasmus exchange. An EU Horizon grant helped fund our first SAR satellite.
The Balrog was a catalyst, acting through the willing descent and total surrender of Gandalf the Grey. Kindred unto the Balrog and Sauron among the Maiar --- the lesser Ainur -- Gandalf plunged into death only to rise transfigured as the White, clothed in glory above his brethren. Thus renewed, he went forth to overthrow the Shadow--yet deliverance came not by his might alone, but through the hands of the meek: mortal Men and Halflings.
Lesson there.
tuomo retweeted
Aina olen kannattanut kansallislaulun vaihtamista Finlandiaan.
On suomalaisen säveltämä hymni, kuvaa paremmin suomalaisten historiallista kokemusta ja taistoa sortoa vastaan, ja sopii muutenkin paremmin sävelkulkunsa johdosta suomalaisen sielunmaisemaan.
Annetaan Virolaisten pitää 'Maamme'. He ovat nyt muutenkin perimältään ja kieleltään saksalaisia lähempänä.
TORILLE!!! 🇫🇮🇫🇮🇫🇮🧬🧬🧬🥳🥳🥳
An inherited genetic mutation may increase lung cancer risk among people who have never smoked, according to a new Science study.
By tracing the ancestry of people carrying the rare EGFR T790M variant, researchers uncovered a shared genetic legacy extending back hundreds of years and concentrated in the southeastern United States.
Learn more in this week’s issue: scim.ag/46q1kUC
ALT An inherited mutation in the EGFR gene (EGFR T790M) increases lung cancer risk. In this illustration, lungs merge with a map of the United States, reflecting the geographic enrichment of the EGFR T790M mutation. By tracing the ancestry of people carrying this mutation, researchers uncovered a shared genetic legacy extending back hundreds of years and concentrated in the southeastern United States. Illustration: Oliver Uberti
Magical timing just few hours after my post this @Nature post comes online 🤣
I trained the fly on the entire corpus of human knowledge predating 1905.🪰
I was not ready for what happened when I prompted it to see if it could come up with the theory of relativity on it's own.. Also asked about NS... 🤯
We have to pace the flyntier!
(sounds on!)
For the first time, scientists have mapped the complete brain and central nervous system of an adult male fruit fly — a key model organism in science. 🪰
Working alongside HHMI Janelia Research Campus and the scientific community, @GoogleResearch scientists and researchers used AI to combine millions of 2D images into 3D neural shapes, reconstructing a record-breaking 166,000+ neurons. This foundational map of the adult male fruit fly brain can help accelerate our understanding of the brain, and is a major milestone in neuroscience.
ALT Vibrant 3D digital reconstruction of a fruit fly brain against a white background, displaying a dense, intricate network of multicolored neural fibers and cell bodies in shades of blue, cyan, orange, and purple.
ALT A complex 3D visualization of a fruit fly brain, featuring a dense, symmetrical network of thousands of tiny, multicolored neurons and fine, interconnected fibers in shades of blue, magenta, orange, and green against a solid white background.
when @JeffDean raises a round he doesn’t estimate a valuation for his company but sets a new objective valuation for the US dollar
Sources: Jeff Dean is raising funds again for Discovery Loop, seeking a valuation of ~$50B; Discovery Loop was raising $1B at a ~$10B valuation a few weeks ago (@thebenbergman / Business Insider)
(Visit Techmeme dot com for the link and full context!)
tuomo retweeted
Forward prediction in single-cell sequencing, virtual cells, virtual tissues, and perturbation experiments are all important future directions. Under scientifically sound methods and rigorous argumentation, they could greatly reduce the cost and time barriers of drug development.
Some speculative thoughts: Virtual-cell-like models such as scGPT and Geneformer attempt to recover the manifold distribution of living cells through “virtual sequencing.” But this is essentially an energy-landscape map. To use a somewhat imperfect analogy (or perhaps not so imperfect if one considers @7uomoki 's earlier information-theoretic perspective), it is a thermodynamic morphology map: you know the possible paths, but not the direction or speed. In contrast, RNA velocity and some time-series data capture the dynamical information at the current node and along the current trajectory, yet lack the overall thermodynamic properties, because the on-the-fly training of velocity models gives them a rather limited field of view without global knowledge. This work injects a GRN to give it a sense of morphology. If we take foundation models like scGPT as the morphology and allow velocity to run on top of it, could that trigger the discovery of many deeper, hidden processes?
I am a complete outsider, having read some papers in this field purely out of interest. My views may not be entirely correct, but the whole process feels somewhat analogous to the physical world and is quite fascinating.
Excited to share our RegVelo paper in Cell
cell.com/cell/fulltext/S0092…
We unify RNA velocity + GRNs into one model → better OOD prediction of perturbations (e.g. gene KOs), with examples incl. neural crest KO predictions 🔬
Big thanks to W Wang, Z Hu & T Sauka-Spengler 🙏
TORILLE!!!! 🇫🇮🇫🇮🇫🇮🤖🤖🤖
Today, we announced a new €13 billion commitment to Finland’s digital and clean energy infrastructure over the next two years — our largest single investment in Europe to date.
Building on 15+ years in Finland, this investment will expand our presence in Hamina and establish new infrastructure in Kajaani, Muhos, and Vaala. During construction, the project is projected to contribute an annual average of €3.6 billion to Finland’s GDP and support over 37,000 jobs nationwide.
>be me, oai
>hear the rumors: ocarina of time remake coming next year
>launch a swarm of 100k internal next gen model agents to complete it latest november 5th
>congratulate folks at nintendo — the closest humans to the game
>find a case of mountain dew
