Cited by 32Machine Learning in BioinformaticsProtein Structure and DynamicsRNA and protein synthesis mechanisms

Learning the language of life with AI

Topol, Eric J.·2025·Science

Abstract

In 2021, a year before ChatGPT took the world by storm amid the excitement about generative artificial intelligence (AI), AlphaFold 2 cracked the 50-year-old protein-folding problem, predicting three-dimensional (3D) structures for more than 200 million proteins from their amino acid sequences. This accomplishment was a precursor to an unprecedented burgeoning of large language models (LLMs) in the life sciences. That was just the beginning. In recent months, we have moved into a hyperaccelerated phase of new foundation models , pretrained on massive datasets, with the ability to perform a wide range of tasks that are helping us understand the structure, biology, evolution, and design of proteins, RNA, DNA, and ligands, as well as their biomolecular interactions. Unlike multimodal LLMs such as GPT-4, Gemini, and Claude, which process text, audio, and images, these large language of life models (LLLMs) are multiomic. That is to say, they are not only multimodal but pertain to different layers of molecular biology. For example, Evo , a foundation model trained on 2.7 million diverse phage and prokaryotic genomes (equivalent to about 300 billion DNA nucleotides), predicts the impact of variants in DNA, RNA, or proteins on structure and function, as well as how essential genes are to cell function, and can generate new DNA sequences.

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  • Subsequent data-driven approaches including statistical machine learning and deep learning significantly improved predictive performance but remained fundamentally reactive, offering recommendations or risk scores without the ability to autonomously plan, act, or adapt over time.

    “Subsequent generations of data-driven approaches, including statistical machine learning and deep learning, significantly improved predictive performance but remained fundamentally reactive, offering recommendations or risk scores without the ability to autonomously plan, act, or adapt over time [2-4].”

Authors
Topol, E. J.
Affiliations
Scripps Research Institute (US)
Corresponding author
Topol, Eric J.
Venue
Science
Published
2025-01-31
Volume
387
Issue
6733
Pages
eadv4414-eadv4414
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W4406970378
Cited by
32
References
0
Citations by year
2026: 15 · 2025: 17
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
protein structure prediction, AlphaFold, foundation models, variant effect prediction, DNA sequence generation, protein design, biomolecular interactions, ChatGPT
MeSH terms
Large Language Models, Artificial Intelligence, Biological Science Disciplines, DNA, Language, Proteins, RNA, Protein Folding

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