I just ran the first n=1 dynamic regulome experiment. On myself. A 72-hour fast where we tracked all 4,000+ components of the genome regulatory 'software' to see how they respond. And over 30% changed, most never mentioned in fasting literature. Why does this matter?. Well, why

report: tech access application:

Do most transcription factors already have an off-switch? . Map of degrons across every human TF from Fia Larsen, @CagiadaMatteo, @_amelie_rocks + team. Could be new handles to design precise gene circuits and leveraged for the 'undruggable' drug hunt.

RT @BowTiedBiotech: 12/ 💬 BTBIO take-away:. Capstan won because it showed human data, modular engineering, and pipeline speed. If you’re b….

Wow! Not every day you see a new class of regulatory element. This “range extender” can't turn genes on, but lets enhancers talk across large distances. Do we know what's binding those tandem [C/T]AATTA motifs? LHX2/LHX9? Excited to see.

RT @minjunesh: Short Sleep Variants Do Not Replicate. In March Kristjan Moore from deCODE genetics emailed me urging me to stop working on….

Paper:

3. Structural models can’t keep up. AlphaFold failed to predict the interactions of DNA-dependent TF–TF complexes. Why?. This is a whole new class of biological interaction and we’re going to need new data, new models, and new assumptions to decode it.

2. These motifs are precise. Most active TF pairs bind within 5bp of each other. A 1bp shift can flip the switch off, may be a way to organize messy inputs and make crisp decisions. And probably a way that evolution programs logic gates into the regulome

1. TFs act in dense combinatorial networks. There are ~1.6 million possible TF–TF pairs in the human genome. This study tested just 58,000 and still uncovered 1,131 new motif binding sites. Many of these sites were invisible to standard motif or accessibility assays

Congrats to @IlyaSokolov314 and team who discovered 2,198 new connections in the regulome. with a very elegant extension of SELEX. They mapped how transcription factors (TFs) work together and illuminate a critical layer of logic in our genome. My 3 takaways

RT @ycombinator: In collaboration with @reindsummit and @newindustrials, we are releasing a request for startups motivated by a simple beli….

@talusbio Link to apply: Preprint describing the tech:

Are you working at the frontier of biology?. We’re looking for a few fellow explorers to map the regulome together. The @talusbio Regulome Early Access Program opens today, join us in charting the cell’s decision-making system in real time. We’ll work side by side to deploy the

Link to primate study: .Senescence-resistant human mesenchymal progenitor cells counter aging in primates: Cell Link to regulome atlas:

Our regulome atlas shows FOXO3 binding DNA across diverse tissues, but AlphaFold, Boltz, etc can't predict a structure. Super strong activity in multiple myeloma (plasma cells cancer). Taking a deeper look into early small molecule FOXO3 activators.

FOXO3 seems to work as a stress and nutrient sensor node within the regulome. When insulin/IGF levels fall, it slides into the nucleus and activates DNA repair, autophagy, antioxidant programs, while shutting off senescence. Strong genetic links to FOXO1 in centinatians too

Added to the 'most wanted transcription factors' list: FOXO3. Profound anti-aging effects in a primate model. Gene-edited stem cells with always-on FOXO3 reversed biological age in 61 tissues (no tumors, sharper brains, younger skin, stronger bones)

Patrick Collison: "We have never cured a complex disease". Maybe we've never had the right data? . Genetic predisposition + environmental factors = complex disease. The regulome integrates environmental inputs to coordinate genomic outputs.

RT @vitrupo: Patrick Collison says humanity has never cured a complex disease. Not cancer. Not Alzheimer’s. Not Type 1 diabetes. His Arc I….