DNA is crucial for life, and its organization has been a significant scientific challenge. GROVER, a model developed by BIOTEC, decodes DNA like text, promising advancements in genomics and personalized medicine.
DNA holds the essential information required to sustain life. Deciphering how this information is stored and organized has been one of the greatest scientific challenges of the past century. Now, with GROVER, a new large language model trained on human DNA, researchers can attempt to decode the intricate information concealed within our genome. Developed by a team at the Biotechnology Center (BIOTEC) of Dresden University of Technology, GROVER treats human DNA as text, learning its rules and context to extract functional information about DNA sequences. Published in Nature Machine Intelligence, this innovative tool has the potential to revolutionize genomics and accelerate personalized medicine.
Since the discovery of the double helix, scientists have sought to understand the information encoded in DNA. 70 years later, it is clear that the information hidden in the DNA is multilayered. Only 1-2 % of the genome consists of genes, the sequences that code for proteins.
"DNA has many functions beyond coding for proteins. Some sequences regulate genes, others serve structural purposes, and most sequences serve multiple functions at once. Currently, we don't understand the meaning of most of the DNA. When it comes to understanding the non-coding regions of the DNA, it seems that we have only started to scratch the surface. This is where AI and large language models can help," says Dr. Anna Poetsch, research group leader at the BIOTEC.
DNA as a Language
Large language models, like GPT, have transformed our understanding of language. Trained exclusively on text, the large language models developed the ability to use the language in many contexts.
"DNA is the code of life. Why not treat it like a language?" says Dr. Poetsch. The Poetsch team trained a large language model on a reference human genome. The resulting tool named GROVER, or "Genome Rules Obtained via Extracted Representations", can be used to extract biological meaning from the DNA.
"GROVER learned the rules of DNA. In terms of language, we are talking about grammar, syntax, and semantics. For DNA this means learning the rules governing the sequences, the order of the nucleotides and sequences, and the meaning of the sequences. Like GPT models learning human languages, GROVER has basically learned how to 'speak' DNA," explains Dr. Melissa Sanabria, the researcher behind the project.
The team showed that GROVER can not only accurately predict the following DNA sequences but can also be used to extract contextual information that has biological meaning, e.g., identify gene promoters or protein binding sites on DNA. GROVER also learns processes that are generally considered to be "epigenetic", i.e., regulatory processes that happen on top of the DNA rather than being encoded.
"It is fascinating that by training GROVER with only the DNA sequence, without any annotations of functions, we are actually able to extract information on biological function. To us, it shows that the function, including some of the epigenetic information, is also encoded in the sequence," says Dr. Sanabria.
The DNA Dictionary
"DNA resembles language. It has four letters that build sequences and the sequences carry a meaning. However, unlike a language, DNA has no defined words," says Dr. Poetsch. DNA consists of four letters (A, T, G, and C) and genes, but there are no predefined sequences of different lengths that combine to build genes or other meaningful sequences.
To train GROVER, the team had to first create a DNA dictionary. They used a trick from compression algorithms. "This step is crucial and sets our DNA language model apart from the previous attempts," says Dr. Poetsch.
"We analyzed the whole genome and looked for combinations of letters that occur most often. We started with two letters and went over the DNA, again and again, to build it up to the most common multi-letter combinations. In this way, in about 600 cycles, we have fragmented the DNA into 'words' that let GROVER perform the best when it comes to predicting the next sequence," explains Dr. Sanabria.
The Promise of AI in Genomics
GROVER promises to unlock the different layers of genetic code. DNA holds key information on what makes us human, our disease predispositions, and our responses to treatments.
"We believe that understanding the rules of DNA through a language model is going to help us uncover the depths of biological meaning hidden in the DNA, advancing both genomics and personalized medicine," says Dr. Poetsch.
Reference: "DNA language model GROVER learns sequence context in the human genome" by Melissa Sanabria, Jonas Hirsch, Pierre M. Joubert and Anna R. Poetsch, 23 July 2024, Nature Machine Intelligence.
DOI: 10.1038/s42256-024-00872-0
News
It’s Not “All in Your Head”: Scientists Develop Revolutionary Blood Test for Chronic Fatigue Syndrome
A 96% accurate blood test for ME/CFS could transform diagnosis and pave the way for future long COVID detection. Researchers from the University of East Anglia and Oxford Biodynamics have created a highly accurate [...]
How Far Can the Body Go? Scientists Find the Ultimate Limit of Human Endurance
Even the most elite endurance athletes can’t outrun biology. A new study finds that humans hit a metabolic ceiling at about 2.5 times their resting energy burn. When ultra-runners take on races that last [...]
World’s Rivers “Overdosing” on Human Antibiotics, Study Finds
Researchers estimate that approximately 8,500 tons of antibiotics enter river systems each year after passing through the human body and wastewater treatment processes. Rivers spanning millions of kilometers across the globe are contaminated with [...]
Yale Scientists Solve a Century-Old Brain Wave Mystery
Yale scientists traced gamma brain waves to thalamus-cortex interactions. The discovery could reveal how brain rhythms shape perception and disease. For more than a century, scientists have observed rhythmic waves of synchronized neuronal activity [...]
Can introducing peanuts early prevent allergies? Real-world data confirms it helps
New evidence from a large U.S. primary care network shows that early peanut introduction, endorsed in 2015 and 2017 guidelines, was followed by a marked decline in clinician-diagnosed peanut and overall food allergies among [...]
Nanoparticle blueprints reveal path to smarter medicines
Lipid nanoparticles (LNPs) are the delivery vehicles of modern medicine, carrying cancer drugs, gene therapies and vaccines into cells. Until recently, many scientists assumed that all LNPs followed more or less the same blueprint, [...]
How nanomedicine and AI are teaming up to tackle neurodegenerative diseases
When I first realized the scale of the challenge posed by neurodegenerative diseases, such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS), I felt simultaneously humbled and motivated. These disorders are not caused [...]
Self-Organizing Light Could Transform Computing and Communications
USC engineers have demonstrated a new kind of optical device that lets light organize its own route using the principles of thermodynamics. Instead of relying on switches or digital control, the light finds its own [...]
Groundbreaking New Way of Measuring Blood Pressure Could Save Thousands of Lives
A new method that improves the accuracy of interpreting blood pressure measurements taken at the ankle could be vital for individuals who are unable to have their blood pressure measured on the arm. A newly developed [...]
Scientist tackles key roadblock for AI in drug discovery
The drug development pipeline is a costly and lengthy process. Identifying high-quality "hit" compounds—those with high potency, selectivity, and favorable metabolic properties—at the earliest stages is important for reducing cost and accelerating the path [...]
Nanoplastics with environmental coatings can sneak past the skin’s defenses
Plastic is ubiquitous in the modern world, and it's notorious for taking a long time to completely break down in the environment - if it ever does. But even without breaking down completely, plastic [...]
Chernobyl scientists discover black fungus feeding on deadly radiation
It looks pretty sinister, but it might actually be incredibly helpful When reactor number four in Chernobyl exploded, it triggered the worst nuclear disaster in history, one which the surrounding area still has not [...]
Long COVID Is Taking A Silent Toll On Mental Health, Here’s What Experts Say
Months after recovering from COVID-19, many people continue to feel unwell. They speak of exhaustion that doesn’t fade, difficulty breathing, or an unsettling mental haze. What’s becoming increasingly clear is that recovery from the [...]
Study Delivers Cancer Drugs Directly to the Tumor Nucleus
A new peptide-based nanotube treatment sneaks chemo into drug-resistant cancer cells, providing a unique workaround to one of oncology’s toughest hurdles. CiQUS researchers have developed a novel molecular strategy that allows a chemotherapy drug to [...]
Scientists Begin $14.2 Million Project To Decode the Body’s “Hidden Sixth Sense”
An NIH-supported initiative seeks to unravel how the nervous system tracks and regulates the body’s internal organs. How does your brain recognize when it’s time to take a breath, when your blood pressure has [...]
Scientists Discover a New Form of Ice That Shouldn’t Exist
Researchers at the European XFEL and DESY are investigating unusual forms of ice that can exist at room temperature when subjected to extreme pressure. Ice comes in many forms, even when made of nothing but water [...]
