I’m very pleased to introduce AlphaGenome 2, @GoogleDeepMind’s next-generation genomics model that deciphers how DNA changes affect cells.

I’m very pleased to introduce AlphaGenome 2, @GoogleDeepMind’s next-generation genomics model that deciphers how DNA changes affect cells.

Cells are the basic units of life and key to our understanding of biology. It is an ongoing challenge to predict how DNA changes affect the functioning of different cells, such as for a heart muscle cell or an immune cell fighting an infection, and to uncover cellular drivers of disease.

To make progress on this challenge, we needed to design the architecture of AlphaGenome 2 so its predictions were conditional on cell types and states. This new design enables AlphaGenome 2 to predict variant effects across hundreds of human cell types and adapt to unseen cell and disease states without retraining.

When evaluated on the TenK10K immune cell dataset, AlphaGenome 2 demonstrated a major leap in accuracy over its predecessor. It reliably identified nearly twice as many causal variants (30% vs. 16%) and directional gene effects (43% vs. 23%) compared to the original AlphaGenome. This step-change improvement in precision helps researchers pinpoint previously overlooked disease-relevant variants with high confidence.

Using analysis on retrospective case studies, we were able to show AG2’s real world utility in disease understanding. A landmark study had previously shown that a variant in a distant regulatory switch drives irritable bowel disease by overactivating the ETS2 gene in gut macrophages. When used to make predictions across various immune cell types in the gut, AlphaGenome 2 singled out the exact causal variant and showed that it selectively boosts the ETS2 gene in gut macrophages, leaving other cell types and genes largely unaffected.

I would like to thank my colleagues Adam Gayoso @adamgayoso, Žiga Avsec @Avsecz, and our entire genomics team for their incredible contributions and dedication to bringing this model to life.

We are making AlphaGenome 2 available for non-commercial academic research via the AlphaGenome API, and soon we will release AlphaGenome 2 Skills in Google Antigravity. I’m incredibly excited to see how scientists around the world use this model to make progress on biological understanding and treating disease.

Read more on our blog here:
https://deepmind.google/blog/alphagenome-2-deciphering-how-cells-read-dna-to-better-understand-disease/