人类基因组所有单碱基变化的预测图谱

September 8, 2026 ScienceHow predicting the molecular impact of every possible single-letter DNA variant in the human genome will help accelerate our understanding of biology.Today, we are introducing AlphaGenome Atlas: a platform (detailed in our paper) containing predictions for the effects of 9 billion single-nucleotide variants — every single-letter change possible — in the human genome. It is the most comprehensive catalogue of how genetic mutations affect molecular biology, and it is available for academic research through an intuitive and free-to-use website portal.DNA is the language of life. Mastering it is a grand challenge that could transform our ability to understand biology and treat disease. But progress has been limited by a fundamental problem: interpreting how genetic variations impact biology at a molecular level. With roughly 9 billion possible single-letter mutations in the human genome, testing each one in the lab is practically impossible.Google DeepMind has already made progress on this challenge with AlphaGenome, an artificial intelligence (AI) model that can predict how genetic variants impact biological processes. AlphaGenome is helpful for analyzing specific variants and has found widespread use in research, but we wanted to show researchers a big-picture view of variants across the entire genome.By precomputing AlphaGenome’s predictions at scale, we have created an easily accessible resource that vastly expands the model's reach. Just as an atlas is a collection of maps, linking together features of the land like altitude and location, AlphaGenome Atlas charts the molecular effects of DNA variants across the genome.To help scientists quickly find the most impactful genetic changes, we are also releasing the AlphaGenome Variant Impact (AVI) score. The AVI combines the strengths of AlphaGenome and AlphaMissense — our model for predicting the impact of protein-altering DNA variants — condensing both models’ predictions into a single number. Now, researchers can rapidly rank variants and interpret their molecular effects at the same time.Our trusted external collaborators have already used AlphaGenome Atlas to identify and experimentally verify key variants in unsolved rare disease research and find rare variants associated with common traits.AlphaGenome Atlas is available today through an intuitive website portal, our AlphaGenome API, and as a skill in Google Antigravity.AlphaGenome AtlasAlphaGenome Atlas is a massive 1-petabyte dataset, more than 30 times larger than the AlphaFold Database. When we expanded the AlphaFold Database in 2022, we grew the 3D structure information available from around 190K experimental structures to more than 200M structure predictions — covering nearly all catalogued proteins known to science. The database provided a portal that researchers with no coding experience could use, providing intuitive visualizations and making it easier to do large-scale protein structure analysis. It quickly became a crucial resource that drove discoveries across the life sciences and continues to accelerate researchers’ important work in countless fields.In building AlphaGenome Atlas, we also aspire to make predictions more accessible and give scientists an intuitive way to explore a vast dataset.AlphaGenome Atlas provides several powerful, interconnected resources, allowing researchers to link variants directly to the functional DNA sequences they disrupt.Molecular effect predictions Atlas contains thousands of molecular effect predictions for each variant, across multiple important aspects of gene regulation, spanning hundreds of human and mouse cell types and tissues. This serves as the starting point for further resources.AVI score A single number describing the impact for each genetic variant.AVI feature attributions Each AVI score is also linked to distinct biological features driving it, such as the aspects of gene regulation predicted by AlphaGenome or the protein impact score from AlphaMissense.DNA sequence motifs A comprehensive collection of over 2,500 recurrent DNA sequences — the "words" of the genome — and their locations.Together, these resources support researchers for a wide range of genetic research tasks, from rapid variant ranking to deep dives into variant functions.Extensive community collaboration guided the design of AlphaGenome Atlas. The AVI score helps researchers rapidly score and rank variants based on their potential impact. Crucially, it works for both coding regions (the 2% of the genome that codes for proteins) and non-coding regions (the remaining 98%), which orchestrates gene activity and houses most trait-associated variants.Our testing shows that the AVI score provides best-in-class performance across many variant pathogenicity and rare disease benchmarks. To help interpret these scores, we also calculated AVI feature attributions that highlight which molecular processes — like RNA splicing or gene expression — are predicted to be most disrupted by each variant.Overview of the AlphaGenome Atlas.(1) Precomputed effects are generated genome-wide for over 9 billion single-nucleotide variants. (2) From this, an allelic-resolution AlphaGenome Variant Impact (AVI) score is derived for each variant. To facilitate variant interpretation, AlphaGenome Atlas then decomposes the AVI score into additive feature contributions across interpretable categories such as chromatin accessibility, splicing, and conservation. (3) The precomputed variant effects, AVI score and the AVI feature attributions are linked, together with a compendium of genome-wide de novo motifs, which enables high-resolution mechanistic insights into variant function.Real-world impact: From rare diseases to population genetics and molecular biologyAlphaGenome Atlas provides a high-resolution, global view of the genome. These large-scale predictions become most useful when applied to targeted research questions. By translating this data into actionable biological insights, our academic partners are already uncovering links between genetic variation and disease.Understanding unsolved rare diseases. A major hurdle in understanding rare diseases is the daunting task of pinpointing the few causal variants hidden among thousands of candidates. In collaboration with the GREGoR Consortium, researchers applied the AVI score to prioritize these needle-in-a-haystack genetic variants for unsolved rare disease research. When Laura Covill and Anne O’Donnell-Luria from the Broad Institute and their colleagues used the AVI score to prioritize variants, driving a rare disease, that were overlooked in previous research, the team discovered a variant affecting a gene called DNM1, which is strongly linked to epileptic encephalopathy.Crucially, the AlphaGenome predictions underlying the AVI score showed exactly how the variant functioned: it created an incorrect splice site (a mistake in the cell’s genetic instructions) that led to an abnormal extension of the resulting protein. Experimental screens validated the research prediction and found nearby variants with similar effects, showing that Atlas is a powerful tool for understanding impactful genomic variation.Mapping rare variants associated with protein levels and complex traits. Moving beyond individual rare disease research, AlphaGenome Atlas can help uncover the genetic architecture of common traits in the general population. Identifying which rare, non-coding variants are associated with a specific trait or disease is notoriously difficult because the sheer volume of harmless genetic changes creates a statistical 'background noise'.To test how AlphaGenome Atlas can improve our ability to find non-coding variants affecting human traits, Gareth Hawkes, a Medical Research Council fellow at the University of Exeter, applied AlphaGenome Atlas to whole-genome data from over 54,000 UK Biobank participants, which made these elusive signals more obvious. By grouping rare variants based on their predicted molecular effects, Hawkes uncovered 22% more non-coding genetic associations, which would otherwise have not been detectable in the statistical noise. This let Hawkes pinpoint specific regulatory variants driving the abundance of critical proteins circulating in the human body, including PLA2G7 (linked to aging) and EGLN1 (a vital cellular oxygen sensor).Taking this approach even further, Hawkes used AlphaGenome Atlas to look at how hundreds of millions of non-coding variants in the UK Biobank might be linked to body mass index. By focusing on the 1% of non-coding variants which Atlas predicts to be most impactful, he identified 19 genetic regions, which could help direct the next stage of targeted research into this trait.Identifying the regulatory ‘words’ of the genome. Atlas can also be used to identify which recurring short sequences, or motifs, are driving different molecular processes in different cell types for different genes. These motifs can provide key clues, such as locating binding sites of transcription factors (proteins that turn genes on or off) and providing additional interpretation of non-coding variants. Julia Zeitlinger and Melanie Weilert at the Stowers Institute for Medical Research used this resource, for example, to categorize which transcription factors only affect the accessibility of DNA versus which ones are also able to turn genes on and off.Accelerating genomic discoveryWith AlphaGenome Atlas we are creating new layers of information that will help further our understanding of the human genetic code. We hope that this will be a valuable resource for scientists, but we also view it as a baseline rather than an endpoint. As our AI models like AlphaGenome improve, our maps of the entire human genome will become increasingly comprehensive and precise.AlphaGenome Atlas is powerful in isolation, but it also represents a step towards our vision of a broad, unified solution for biologists. Its resources can be integrated into our broader agentic systems, like Google Antigravity, to help enhance end-to-end scientific workflows.It is also important that AlphaGenome Atlas’ scientific knowledge is widely available, so we have made it accessible for non-commercial use through our website from today, as well as for commercial use on Google Cloud soon. (The AlphaGenome base model is already available for academic use on GitHub and via the AlphaGenome API, and also is available for commercial use on Cloud via Model Garden).Together, these tools will enable researchers and industry partners to accelerate the pace of biological discovery: finding novel therapeutic targets, better understanding genetic disorders, and driving the next wave of targeted experimental validation.AcknowledgementsWe are grateful to our research collaborators at University of Exeter, Broad Institute, Boston Children’s Hospital, Stowers Institute for Medical Research, Harvard University, Memorial Sloan Kettering Cancer Center, Center for Genomic Medicine at Massachusetts General Hospital, and the University of Kansas Medical Center.This work was done thanks to the contributions of Jun Cheng, Kyle R. Taylor, Lauren Nicolaisen, Joshua Pan, Clare Bycroft, Matteo Perino, Tom Ward, Raina W. Thomas, Natasha Latysheva, Gareth Hawkes, Laura E. Covill, Melanie Weilert, Maile J. Hirschmann, Xi Dawn Chen, Robin N Beaumont, V Kartik Chundru, Michael N Weedon, Simon Bourdareau, Hoyin Chu, Dhavi Hariharan, Thais Kagohara, Lucas Tenório, Yosuke Ushigome, Amanda Stafford, Courtney A. Shearer, Barbara Ikica, Ada Fang, Mouad Naciri, Victoria Johnston, Richard Green, Elisa Lai Hong Wong, Vincent Dutordoir, Anne Mottram, Adam Gayoso, Eirini Arvaniti, Guido Novati, Heidi L. Rehm, Fei Chen, Caleb A. Lareau, Caroline F Wright, Anne O'Donnell-Luria, Julia Zeitlinger, Pushmeet Kohli, Žiga Avsec.We wish to thank our teammates and collaborators for their technical support, feedback, including Kathryn Tunyasuvunakool, Alexander Karollus, Risha Patel, Francesca Pietra, Alisha Eastep, Doga Fadillioglu, Charlie Taylor, Raphael Aboyeji, Uchechi Okereke, Gemma Gibbs, Olufemi Duduyemi, Juan Mateos-Garcia, Mariana Felix, Sahar Abdulrahman, Antonia Mould, Rachael Tremlett, Chang Yun, Salil Deshpande, Anshul Kundaje, Samantha Bryen, Greg Findlay, Phoebe Dace, Kinga Bujakowska, Emma Sherrill, Aubrie Soucy Verran, Boxun Zhao, Tim Yu, Francesca Pietra, Brendah Namugamba, Cassie Gray, Daniel MacArthur, Lingyi Wang, Marc Mansour, Mohamad Hajjari, Mounica Vallurupalli, Philip Montgomery, Phoebe Dace, Roisin Sullivan, Sam Bryen, Teresa Niccoli,Finally we wish to thank Evie Gray, Adriana Fernandez Lara, Alex Wilkins, Danielle Breen, Mariana Montes, Inês Ayer, Ryan Smith, Ross West and Gaby Pearl for their expertise in communicating this work.AlphaGenomeAlphaGenome: AI for better understanding the genome