
PhD candidate studying the role of somatic mutations in human aging with Vijg & Sidoli Labs @EinsteinMed
Bronx, NY
Joined June 2018
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Ronnie Cutler retweeted
Our paper is out in @NatureAging. We looked for factors that make old cells' gene expression young without erasing their identity. SRSF1 came out as a promising rejuvenation target that reduced aging hallmarks in human cells and extended median lifespan of aged mice by 14%.
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ALT Watercolor-style graphic of two overlapping cells split by a curved diagonal. On the left, a muted gray cell with a dark nucleus and faint white circuit traces. On the right, the same form in luminous blue, its circuitry lit up. Short dashes standing for RNA transcripts scatter loosely in gray on the left and fan outward in blue and pale green arcs on the right. Art by Helen H. Wang.
Finally, confidence scores!
AlphaGenome made predictions for all 9B single nucleotide variants, but can you trust them? The models are still far from accurate!
Check out our updated preprint (now a full paper, upgraded from our early pre-CSHL AI symposium draft):
biorxiv.org/content/10.64898…
Ronnie Cutler retweeted
Very good news for the future of longevity trials!
HHS has announced the SURPASS program to develop new methods to make clinical trials faster, less expensive, and less burdensome to patients.
Researchers could make better decisions as evidence accumulates and test new treatments without rebuilding the infrastructure for each study.
For longevity, more efficient trials could expand the range of treatments we can afford to test. Promising biology can only become medicine if we can study it in people. When trials are too costly or difficult to run, treatments can be ruled out before we learn whether they work.
SURPASS could give more longevity medicines that chance:
hhs.gov/press-room/hhs-arpa-…
Ronnie Cutler retweeted
We are all mosaics with our cells accumulating somatic mutations as we age. Now that is getting fully comprehensively quantified @CellCellPress
cell.com/cell/fulltext/S0092…
Ronnie Cutler retweeted
Our Nature Medicine paper is out: menopause isn't a slow slope. Across 300M+ lab tests from 1M+ women, many body systems jump at the final menstrual period. Men show no such jump. 1/4
nature.com/articles/s41591-0…
Ronnie Cutler retweeted
Thrilled to share that our work reconstructing a cell fate map of the mouse embryo is out now in @CellCellPress! doi.org/10.1016/j.cell.2026.…
Ronnie Cutler retweeted
Incredibly, incredibly excited to introduce SpliceAI2, the next generation of splicing prediction! 🧬🚀🧵
Ronnie Cutler retweeted
Out now in @CellCellPress: ✨SPARCS✨, a
platform for discovering the genes behind complex cellular phenotypes.
SPARCS combines Al-powered image analysis with automated laser microdissection to precisely isolate cells from large mutant libraries.
Paper and highlights👇(1/9)
Ronnie Cutler retweeted
Just a few quick things.
1. Nice rigorous study of the importance of being careful with performance metrics and taking into account data issues.
2. This should be done BEFOFE one fits big models & make lots of big claims. Nevertheless better late than never. 2/
The "Single-cell foundation models don't work for perturbation prediction" narrative was a measurement problem.
Our new paper is out in @NatureBiotech : "Deep Learning Perturbation Models Can Outperform Baselines on Calibrated Metrics"
Last year, several papers concluded that deep learning perturbation models couldn't beat simple baselines, a finding that cast doubt on the entire Virtual Cell direction.
We asked a different question: can the metrics used in those comparisons reliably tell a good prediction from a bad one?
Often, they can't.
Common metrics like MSE and control-referenced Pearson Δ frequently rank uninformative baselines above positive controls. With calibrated alternatives (eg, WMSE, weighted R²Δ, NIR), deep learning models do outperform mean, control, and linear baselines.
The data matters too. Norman19 is approximately 96% additive, and models see less than 1% of possible gene combinations during training. The ceiling for beating an additive baseline is nearly zero, and the training signal for non-additive interactions is almost absent. Some dataset rankings aren't model rankings, but just noise!
To address this, we developed the Dynamic Range Fraction (DRF): a measure of metric calibration. Before trusting a model ranking, verify that your benchmark can detect a useful prediction at all.
The models aren't shiny toys. The field just needed better rulers.
Paper: nature.com/articles/s41587-0…
Code: github.com/shiftbioscience/P…
Huge congratulations to the first authors @Henrymiller2012 and Gabriel Mejia, and the team of Shift Bio!
Ronnie Cutler retweeted
Written in development and lost in ageing: the grammar of cellular identity
nature.com/articles/s41586-0…
Ronnie Cutler retweeted
Interpreting human genetic variation at atomic resolution
nature.com/articles/s41588-0…
Ronnie Cutler retweeted
Protein interactions reveal the hidden wiring of the genome
nature.com/articles/s41588-0…
Some seem more like engineering problems but aging seems more in reach than figuring out the origin of life
In light of the progress in mathematics, we at Edison Scientific and FutureHouse have assembled a set of Millennium Problems for Biology. They are chosen to be very hard to solve but very easy to validate in a simple laboratory environment. Any of these, if solved, would mark a major advance in biotechnology, and most of them would contribute materially towards curing disease. These are, in some sense, the “last reasonable eval” for AI in biology. This was work primarily by @MichaelaThinks and myself, with contributions from many others.
Short descriptions below. The full descriptions of the problems with acceptance criteria are at the Bio Millennium Problems website, linked in the next post. Share more if you have ideas. If they meet our criteria, we’ll add them to our list (with attribution and permission).
Ronnie Cutler retweeted
Cell–cell interactions are key to all biological processes, but there hasn't been a good way to perform inter-cellular screens for genetic regulators of these interactions in vivo.
We developed match-seq (multiplexed associative tagging of cell interaction histories) - using engineered virus-like particles to transfer barcoded mRNAs from 'sender' to neighboring 'receiver' cells, so you can reconstruct cellular interactions with sequencing alone, no imaging required.
We coupled match-seq with CRISPR + scRNA-seq in cancer, revealing cancer-immune interaction neighborhoods at scale, and new cancer genes that can be targeted for tumor rejection via immune cell interactions.
Led by the brilliant @peterdu_ with Bassik lab!
biorxiv.org/content/10.64898…
Ronnie Cutler retweeted
Beautiful paper on how to tease apart cis vs. trans contributions to differences in gene expression. Work of Ingileif Hallgrímsdóttir and Maria Carilli just out in Genetics academic.oup.com/genetics/ad…
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Ronnie Cutler retweeted
cGAS-deficient mice display premature aging associated with derepression of LINE1 elements and inflammation
nature.com/articles/s43587-0…
Ronnie Cutler retweeted
Inspired by Gibson cloning, we describe prime assembly, now published, for in cellulo targeted integration of gene-sized DNA fragments using prime editing. nature.com/articles/s41586-0…
Ronnie Cutler retweeted
When we started Loyal there was no FDA pathway for a any lifespan extension drug.
Today the FDA accepted our third one!
LOY-003, our daily pill for helping large dogs live longer (and healthier) lives, has earned RXE efficacy approval.
Ronnie Cutler retweeted
Millions of PBMCs have been analyzed by scRNA-seq. Have we seen it all ?
We profiled thousands of single PBMCs — proteomes and transcriptomes side by side — and uncovered functional coordination undetectable in the deepest scRNA-seq we could perform.
biorxiv.org/content/10.64898…
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Ronnie Cutler retweeted
Check out our new preprint on thousands of novel recursive exons in the human genome (if you don't know about recursive exons, they are pretty cool), led by PhD student David Bass: biorxiv.org/content/10.64898…



























