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    2023-24 Takeda Fellows: Advancing research at the intersection of AI and health

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    The School of Engineering has selected 13 new Takeda Fellows for the 2023-24 academic year. With support from Takeda, the graduate students will conduct pathbreaking research ranging from remote health monitoring for virtual clinical trials to ingestible devices for at-home, long-term diagnostics.

    Now in its fourth year, the MIT-Takeda Program, a collaboration between MIT’s School of Engineering and Takeda, fuels the development and application of artificial intelligence capabilities to benefit human health and drug development. Part of the Abdul Latif Jameel Clinic for Machine Learning in Health, the program coalesces disparate disciplines, merges theory and practical implementation, combines algorithm and hardware innovations, and creates multidimensional collaborations between academia and industry.

    The 2023-24 Takeda Fellows are:

    Adam Gierlach

    Adam Gierlach is a PhD candidate in the Department of Electrical Engineering and Computer Science. Gierlach’s work combines innovative biotechnology with machine learning to create ingestible devices for advanced diagnostics and delivery of therapeutics. In his previous work, Gierlach developed a non-invasive, ingestible device for long-term gastric recordings in free-moving patients. With the support of a Takeda Fellowship, he will build on this pathbreaking work by developing smart, energy-efficient, ingestible devices powered by application-specific integrated circuits for at-home, long-term diagnostics. These revolutionary devices — capable of identifying, characterizing, and even correcting gastrointestinal diseases — represent the leading edge of biotechnology. Gierlach’s innovative contributions will help to advance fundamental research on the enteric nervous system and help develop a better understanding of gut-brain axis dysfunctions in Parkinson’s disease, autism spectrum disorder, and other prevalent disorders and conditions.

    Vivek Gopalakrishnan

    Vivek Gopalakrishnan is a PhD candidate in the Harvard-MIT Program in Health Sciences and Technology. Gopalakrishnan’s goal is to develop biomedical machine-learning methods to improve the study and treatment of human disease. Specifically, he employs computational modeling to advance new approaches for minimally invasive, image-guided neurosurgery, offering a safe alternative to open brain and spinal procedures. With the support of a Takeda Fellowship, Gopalakrishnan will develop real-time computer vision algorithms that deliver high-quality, 3D intraoperative image guidance by extracting and fusing information from multimodal neuroimaging data. These algorithms could allow surgeons to reconstruct 3D neurovasculature from X-ray angiography, thereby enhancing the precision of device deployment and enabling more accurate localization of healthy versus pathologic anatomy.

    Hao He

    Hao He is a PhD candidate in the Department of Electrical Engineering and Computer Science. His research interests lie at the intersection of generative AI, machine learning, and their applications in medicine and human health, with a particular emphasis on passive, continuous, remote health monitoring to support virtual clinical trials and health-care management. More specifically, He aims to develop trustworthy AI models that promote equitable access and deliver fair performance independent of race, gender, and age. In his past work, He has developed monitoring systems applied in clinical studies of Parkinson’s disease, Alzheimer’s disease, and epilepsy. Supported by a Takeda Fellowship, He will develop a novel technology for the passive monitoring of sleep stages (using radio signaling) that seeks to address existing gaps in performance across different demographic groups. His project will tackle the problem of imbalance in available datasets and account for intrinsic differences across subpopulations, using generative AI and multi-modality/multi-domain learning, with the goal of learning robust features that are invariant to different subpopulations. He’s work holds great promise for delivering advanced, equitable health-care services to all people and could significantly impact health care and AI.

    Chengyi Long

    Chengyi Long is a PhD candidate in the Department of Civil and Environmental Engineering. Long’s interdisciplinary research integrates the methodology of physics, mathematics, and computer science to investigate questions in ecology. Specifically, Long is developing a series of potentially groundbreaking techniques to explain and predict the temporal dynamics of ecological systems, including human microbiota, which are essential subjects in health and medical research. His current work, supported by a Takeda Fellowship, is focused on developing a conceptual, mathematical, and practical framework to understand the interplay between external perturbations and internal community dynamics in microbial systems, which may serve as a key step toward finding bio solutions to health management. A broader perspective of his research is to develop AI-assisted platforms to anticipate the changing behavior of microbial systems, which may help to differentiate between healthy and unhealthy hosts and design probiotics for the prevention and mitigation of pathogen infections. By creating novel methods to address these issues, Long’s research has the potential to offer powerful contributions to medicine and global health.

    Omar Mohd

    Omar Mohd is a PhD candidate in the Department of Electrical Engineering and Computer Science. Mohd’s research is focused on developing new technologies for the spatial profiling of microRNAs, with potentially important applications in cancer research. Through innovative combinations of micro-technologies and AI-enabled image analysis to measure the spatial variations of microRNAs within tissue samples, Mohd hopes to gain new insights into drug resistance in cancer. This work, supported by a Takeda Fellowship, falls within the emerging field of spatial transcriptomics, which seeks to understand cancer and other diseases by examining the relative locations of cells and their contents within tissues. The ultimate goal of Mohd’s current project is to find multidimensional patterns in tissues that may have prognostic value for cancer patients. One valuable component of his work is an open-source AI program developed with collaborators at Beth Israel Deaconess Medical Center and Harvard Medical School to auto-detect cancer epithelial cells from other cell types in a tissue sample and to correlate their abundance with the spatial variations of microRNAs. Through his research, Mohd is making innovative contributions at the interface of microsystem technology, AI-based image analysis, and cancer treatment, which could significantly impact medicine and human health.

    Sanghyun Park

    Sanghyun Park is a PhD candidate in the Department of Mechanical Engineering. Park specializes in the integration of AI and biomedical engineering to address complex challenges in human health. Drawing on his expertise in polymer physics, drug delivery, and rheology, his research focuses on the pioneering field of in-situ forming implants (ISFIs) for drug delivery. Supported by a Takeda Fellowship, Park is currently developing an injectable formulation designed for long-term drug delivery. The primary goal of his research is to unravel the compaction mechanism of drug particles in ISFI formulations through comprehensive modeling and in-vitro characterization studies utilizing advanced AI tools. He aims to gain a thorough understanding of this unique compaction mechanism and apply it to drug microcrystals to achieve properties optimal for long-term drug delivery. Beyond these fundamental studies, Park’s research also focuses on translating this knowledge into practical applications in a clinical setting through animal studies specifically aimed at extending drug release duration and improving mechanical properties. The innovative use of AI in developing advanced drug delivery systems, coupled with Park’s valuable insights into the compaction mechanism, could contribute to improving long-term drug delivery. This work has the potential to pave the way for effective management of chronic diseases, benefiting patients, clinicians, and the pharmaceutical industry.

    Huaiyao Peng

    Huaiyao Peng is a PhD candidate in the Department of Biological Engineering. Peng’s research interests are focused on engineered tissue, microfabrication platforms, cancer metastasis, and the tumor microenvironment. Specifically, she is advancing novel AI techniques for the development of pre-cancer organoid models of high-grade serous ovarian cancer (HGSOC), an especially lethal and difficult-to-treat cancer, with the goal of gaining new insights into progression and effective treatments. Peng’s project, supported by a Takeda Fellowship, will be one of the first to use cells from serous tubal intraepithelial carcinoma lesions found in the fallopian tubes of many HGSOC patients. By examining the cellular and molecular changes that occur in response to treatment with small molecule inhibitors, she hopes to identify potential biomarkers and promising therapeutic targets for HGSOC, including personalized treatment options for HGSOC patients, ultimately improving their clinical outcomes. Peng’s work has the potential to bring about important advances in cancer treatment and spur innovative new applications of AI in health care. 

    Priyanka Raghavan

    Priyanka Raghavan is a PhD candidate in the Department of Chemical Engineering. Raghavan’s research interests lie at the frontier of predictive chemistry, integrating computational and experimental approaches to build powerful new predictive tools for societally important applications, including drug discovery. Specifically, Raghavan is developing novel models to predict small-molecule substrate reactivity and compatibility in regimes where little data is available (the most realistic regimes). A Takeda Fellowship will enable Raghavan to push the boundaries of her research, making innovative use of low-data and multi-task machine learning approaches, synthetic chemistry, and robotic laboratory automation, with the goal of creating an autonomous, closed-loop system for the discovery of high-yielding organic small molecules in the context of underexplored reactions. Raghavan’s work aims to identify new, versatile reactions to broaden a chemist’s synthetic toolbox with novel scaffolds and substrates that could form the basis of essential drugs. Her work has the potential for far-reaching impacts in early-stage, small-molecule discovery and could help make the lengthy drug-discovery process significantly faster and cheaper.

    Zhiye Song

    Zhiye “Zoey” Song is a PhD candidate in the Department of Electrical Engineering and Computer Science. Song’s research integrates cutting-edge approaches in machine learning (ML) and hardware optimization to create next-generation, wearable medical devices. Specifically, Song is developing novel approaches for the energy-efficient implementation of ML computation in low-power medical devices, including a wearable ultrasound “patch” that captures and processes images for real-time decision-making capabilities. Her recent work, conducted in collaboration with clinicians, has centered on bladder volume monitoring; other potential applications include blood pressure monitoring, muscle diagnosis, and neuromodulation. With the support of a Takeda Fellowship, Song will build on that promising work and pursue key improvements to existing wearable device technologies, including developing low-compute and low-memory ML algorithms and low-power chips to enable ML on smart wearable devices. The technologies emerging from Song’s research could offer exciting new capabilities in health care, enabling powerful and cost-effective point-of-care diagnostics and expanding individual access to autonomous and continuous medical monitoring.

    Peiqi Wang

    Peiqi Wang is a PhD candidate in the Department of Electrical Engineering and Computer Science. Wang’s research aims to develop machine learning methods for learning and interpretation from medical images and associated clinical data to support clinical decision-making. He is developing a multimodal representation learning approach that aligns knowledge captured in large amounts of medical image and text data to transfer this knowledge to new tasks and applications. Supported by a Takeda Fellowship, Wang will advance this promising line of work to build robust tools that interpret images, learn from sparse human feedback, and reason like doctors, with potentially major benefits to important stakeholders in health care.

    Oscar Wu

    Haoyang “Oscar” Wu is a PhD candidate in the Department of Chemical Engineering. Wu’s research integrates quantum chemistry and deep learning methods to accelerate the process of small-molecule screening in the development of new drugs. By identifying and automating reliable methods for finding transition state geometries and calculating barrier heights for new reactions, Wu’s work could make it possible to conduct the high-throughput ab initio calculations of reaction rates needed to screen the reactivity of large numbers of active pharmaceutical ingredients (APIs). A Takeda Fellowship will support his current project to: (1) develop open-source software for high-throughput quantum chemistry calculations, focusing on the reactivity of drug-like molecules, and (2) develop deep learning models that can quantitatively predict the oxidative stability of APIs. The tools and insights resulting from Wu’s research could help to transform and accelerate the drug-discovery process, offering significant benefits to the pharmaceutical and medical fields and to patients.

    Soojung Yang

    Soojung Yang is a PhD candidate in the Department of Materials Science and Engineering. Yang’s research applies cutting-edge methods in geometric deep learning and generative modeling, along with atomistic simulations, to better understand and model protein dynamics. Specifically, Yang is developing novel tools in generative AI to explore protein conformational landscapes that offer greater speed and detail than physics-based simulations at a substantially lower cost. With the support of a Takeda Fellowship, she will build upon her successful work on the reverse transformation of coarse-grained proteins to the all-atom resolution, aiming to build machine-learning models that bridge multiple size scales of protein conformation diversity (all-atom, residue-level, and domain-level). Yang’s research holds the potential to provide a powerful and widely applicable new tool for researchers who seek to understand the complex protein functions at work in human diseases and to design drugs to treat and cure those diseases.

    Yuzhe Yang

    Yuzhe Yang is a PhD candidate in the Department of Electrical Engineering and Computer Science. Yang’s research interests lie at the intersection of machine learning and health care. In his past and current work, Yang has developed and applied innovative machine-learning models that address key challenges in disease diagnosis and tracking. His many notable achievements include the creation of one of the first machine learning-based solutions using nocturnal breathing signals to detect Parkinson’s disease (PD), estimate disease severity, and track PD progression. With the support of a Takeda Fellowship, Yang will expand this promising work to develop an AI-based diagnosis model for Alzheimer’s disease (AD) using sleep-breathing data that is significantly more reliable, flexible, and economical than current diagnostic tools. This passive, in-home, contactless monitoring system — resembling a simple home Wi-Fi router — will also enable remote disease assessment and continuous progression tracking. Yang’s groundbreaking work has the potential to advance the diagnosis and treatment of prevalent diseases like PD and AD, and it offers exciting possibilities for addressing many health challenges with reliable, affordable machine-learning tools.  More

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      Neurodegenerative disease can progress in newly identified patterns

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      Neurodegenerative diseases — like amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), Alzheimer’s, and Parkinson’s — are complicated, chronic ailments that can present with a variety of symptoms, worsen at different rates, and have many underlying genetic and environmental causes, some of which are unknown. ALS, in particular, affects voluntary muscle movement and is always fatal, but while most people survive for only a few years after diagnosis, others live with the disease for decades. Manifestations of ALS can also vary significantly; often slower disease development correlates with onset in the limbs and affecting fine motor skills, while the more serious, bulbar ALS impacts swallowing, speaking, breathing, and mobility. Therefore, understanding the progression of diseases like ALS is critical to enrollment in clinical trials, analysis of potential interventions, and discovery of root causes.

      However, assessing disease evolution is far from straightforward. Current clinical studies typically assume that health declines on a downward linear trajectory on a symptom rating scale, and use these linear models to evaluate whether drugs are slowing disease progression. However, data indicate that ALS often follows nonlinear trajectories, with periods where symptoms are stable alternating with periods when they are rapidly changing. Since data can be sparse, and health assessments often rely on subjective rating metrics measured at uneven time intervals, comparisons across patient populations are difficult. These heterogenous data and progression, in turn, complicate analyses of invention effectiveness and potentially mask disease origin.

      Now, a new machine-learning method developed by researchers from MIT, IBM Research, and elsewhere aims to better characterize ALS disease progression patterns to inform clinical trial design.

      “There are groups of individuals that share progression patterns. For example, some seem to have really fast-progressing ALS and others that have slow-progressing ALS that varies over time,” says Divya Ramamoorthy PhD ’22, a research specialist at MIT and lead author of a new paper on the work that was published this month in Nature Computational Science. “The question we were asking is: can we use machine learning to identify if, and to what extent, those types of consistent patterns across individuals exist?”

      Their technique, indeed, identified discrete and robust clinical patterns in ALS progression, many of which are non-linear. Further, these disease progression subtypes were consistent across patient populations and disease metrics. The team additionally found that their method can be applied to Alzheimer’s and Parkinson’s diseases as well.

      Joining Ramamoorthy on the paper are MIT-IBM Watson AI Lab members Ernest Fraenkel, a professor in the MIT Department of Biological Engineering; Research Scientist Soumya Ghosh of IBM Research; and Principal Research Scientist Kenney Ng, also of IBM Research. Additional authors include Kristen Severson PhD ’18, a senior researcher at Microsoft Research and former member of the Watson Lab and of IBM Research; Karen Sachs PhD ’06 of Next Generation Analytics; a team of researchers with Answer ALS; Jonathan D. Glass and Christina N. Fournier of the Emory University School of Medicine; the Pooled Resource Open-Access ALS Clinical Trials Consortium; ALS/MND Natural History Consortium; Todd M. Herrington of Massachusetts General Hospital (MGH) and Harvard Medical School; and James D. Berry of MGH.

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      MIT Professor Ernest Fraenkel describes early stages of his research looking at root causes of amyotrophic lateral sclerosis (ALS).

      Reshaping health decline

      After consulting with clinicians, the team of machine learning researchers and neurologists let the data speak for itself. They designed an unsupervised machine-learning model that employed two methods: Gaussian process regression and Dirichlet process clustering. These inferred the health trajectories directly from patient data and automatically grouped similar trajectories together without prescribing the number of clusters or the shape of the curves, forming ALS progression “subtypes.” Their method incorporated prior clinical knowledge in the way of a bias for negative trajectories — consistent with expectations for neurodegenerative disease progressions — but did not assume any linearity. “We know that linearity is not reflective of what’s actually observed,” says Ng. “The methods and models that we use here were more flexible, in the sense that, they capture what was seen in the data,” without the need for expensive labeled data and prescription of parameters.

      Primarily, they applied the model to five longitudinal datasets from ALS clinical trials and observational studies. These used the gold standard to measure symptom development: the ALS functional rating scale revised (ALSFRS-R), which captures a global picture of patient neurological impairment but can be a bit of a “messy metric.” Additionally, performance on survivability probabilities, forced vital capacity (a measurement of respiratory function), and subscores of ALSFRS-R, which looks at individual bodily functions, were incorporated.

      New regimes of progression and utility

      When their population-level model was trained and tested on these metrics, four dominant patterns of disease popped out of the many trajectories — sigmoidal fast progression, stable slow progression, unstable slow progression, and unstable moderate progression — many with strong nonlinear characteristics. Notably, it captured trajectories where patients experienced a sudden loss of ability, called a functional cliff, which would significantly impact treatments, enrollment in clinical trials, and quality of life.

      The researchers compared their method against other commonly used linear and nonlinear approaches in the field to separate the contribution of clustering and linearity to the model’s accuracy. The new work outperformed them, even patient-specific models, and found that subtype patterns were consistent across measures. Impressively, when data were withheld, the model was able to interpolate missing values, and, critically, could forecast future health measures. The model could also be trained on one ALSFRS-R dataset and predict cluster membership in others, making it robust, generalizable, and accurate with scarce data. So long as 6-12 months of data were available, health trajectories could be inferred with higher confidence than conventional methods.

      The researchers’ approach also provided insights into Alzheimer’s and Parkinson’s diseases, both of which can have a range of symptom presentations and progression. For Alzheimer’s, the new technique could identify distinct disease patterns, in particular variations in the rates of conversion of mild to severe disease. The Parkinson’s analysis demonstrated a relationship between progression trajectories for off-medication scores and disease phenotypes, such as the tremor-dominant or postural instability/gait difficulty forms of Parkinson’s disease.

      The work makes significant strides to find the signal amongst the noise in the time-series of complex neurodegenerative disease. “The patterns that we see are reproducible across studies, which I don’t believe had been shown before, and that may have implications for how we subtype the [ALS] disease,” says Fraenkel. As the FDA has been considering the impact of non-linearity in clinical trial designs, the team notes that their work is particularly pertinent.

      As new ways to understand disease mechanisms come online, this model provides another tool to pick apart illnesses like ALS, Alzheimer’s, and Parkinson’s from a systems biology perspective.

      “We have a lot of molecular data from the same patients, and so our long-term goal is to see whether there are subtypes of the disease,” says Fraenkel, whose lab looks at cellular changes to understand the etiology of diseases and possible targets for cures. “One approach is to start with the symptoms … and see if people with different patterns of disease progression are also different at the molecular level. That might lead you to a therapy. Then there’s the bottom-up approach, where you start with the molecules” and try to reconstruct biological pathways that might be affected. “We’re going [to be tackling this] from both ends … and finding if something meets in the middle.”

      This research was supported, in part, by the MIT-IBM Watson AI Lab, the Muscular Dystrophy Association, Department of Veterans Affairs of Research and Development, the Department of Defense, NSF Gradate Research Fellowship Program, Siebel Scholars Fellowship, Answer ALS, the United States Army Medical Research Acquisition Activity, National Institutes of Health, and the NIH/NINDS. More

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      An “oracle” for predicting the evolution of gene regulation

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      Despite the sheer number of genes that each human cell contains, these so-called “coding” DNA sequences comprise just 1 percent of our entire genome. The remaining 99 percent is made up of “non-coding” DNA — which, unlike coding DNA, does not carry the instructions to build proteins.

      One vital function of this non-coding DNA, also called “regulatory” DNA, is to help turn genes on and off, controlling how much (if any) of a protein is made. Over time, as cells replicate their DNA to grow and divide, mutations often crop up in these non-coding regions — sometimes tweaking their function and changing the way they control gene expression. Many of these mutations are trivial, and some are even beneficial. Occasionally, though, they can be associated with increased risk of common diseases, such as Type 2 diabetes, or more life-threatening ones, including cancer.

      To better understand the repercussions of such mutations, researchers have been hard at work on mathematical maps that allow them to look at an organism’s genome, predict which genes will be expressed, and determine how that expression will affect the organism’s observable traits. These maps, called fitness landscapes, were conceptualized roughly a century ago to understand how genetic makeup influences one common measure of organismal fitness in particular: reproductive success. Early fitness landscapes were very simple, often focusing on a limited number of mutations. Much richer datasets are now available, but researchers still require additional tools to characterize and visualize such complex data. This ability would not only facilitate a better understanding of how individual genes have evolved over time, but would also help to predict what sequence and expression changes might occur in the future.

      In a new study published on March 9 in Nature, a team of scientists has developed a framework for studying the fitness landscapes of regulatory DNA. They created a neural network model that, when trained on hundreds of millions of experimental measurements, was capable of predicting how changes to these non-coding sequences in yeast affected gene expression. They also devised a unique way of representing the landscapes in two dimensions, making it easy to understand the past and forecast the future evolution of non-coding sequences in organisms beyond yeast — and even design custom gene expression patterns for gene therapies and industrial applications.

      “We now have an ‘oracle’ that can be queried to ask: What if we tried all possible mutations of this sequence? Or, what new sequence should we design to give us a desired expression?” says Aviv Regev, a professor of biology at MIT (on leave), core member of the Broad Institute of Harvard and MIT (on leave), head of Genentech Research and Early Development, and the study’s senior author. “Scientists can now use the model for their own evolutionary question or scenario, and for other problems like making sequences that control gene expression in desired ways. I am also excited about the possibilities for machine learning researchers interested in interpretability; they can ask their questions in reverse, to better understand the underlying biology.”

      Prior to this study, many researchers had simply trained their models on known mutations (or slight variations thereof) that exist in nature. However, Regev’s team wanted to go a step further by creating their own unbiased models capable of predicting an organism’s fitness and gene expression based on any possible DNA sequence — even sequences they’d never seen before. This would also enable researchers to use such models to engineer cells for pharmaceutical purposes, including new treatments for cancer and autoimmune disorders.

      To accomplish this goal, Eeshit Dhaval Vaishnav, a graduate student at MIT and co-first author; Carl de Boer, now an assistant professor at the University of British Columbia; and their colleagues created a neural network model to predict gene expression. They trained it on a dataset generated by inserting millions of totally random non-coding DNA sequences into yeast, and observing how each random sequence affected gene expression. They focused on a particular subset of non-coding DNA sequences called promoters, which serve as binding sites for proteins that can switch nearby genes on or off.

      “This work highlights what possibilities open up when we design new kinds of experiments to generate the right data to train models,” Regev says. “In the broader sense, I believe these kinds of approaches will be important for many problems — like understanding genetic variants in regulatory regions that confer disease risk in the human genome, but also for predicting the impact of combinations of mutations, or designing new molecules.”

      Regev, Vaishnav, de Boer, and their coauthors went on to test their model’s predictive abilities in a variety of ways, in order to show how it could help demystify the evolutionary past — and possible future — of certain promoters. “Creating an accurate model was certainly an accomplishment, but, to me, it was really just a starting point,” Vaishnav explains.

      First, to determine whether their model could help with synthetic biology applications like producing antibiotics, enzymes, and food, the researchers practiced using it to design promoters that could generate desired expression levels for any gene of interest. They then scoured other scientific papers to identify fundamental evolutionary questions, in order to see if their model could help answer them. The team even went so far as to feed their model a real-world population dataset from one existing study, which contained genetic information from yeast strains around the world. In doing so, they were able to delineate thousands of years of past selection pressures that sculpted the genomes of today’s yeast.

      But, in order to create a powerful tool that could probe any genome, the researchers knew they’d need to find a way to forecast the evolution of non-coding sequences even without such a comprehensive population dataset. To address this goal, Vaishnav and his colleagues devised a computational technique that allowed them to plot the predictions from their framework onto a two-dimensional graph. This helped them show, in a remarkably simple manner, how any non-coding DNA sequence would affect gene expression and fitness, without needing to conduct any time-consuming experiments at the lab bench.

      “One of the unsolved problems in fitness landscapes was that we didn’t have an approach for visualizing them in a way that meaningfully captured the evolutionary properties of sequences,” Vaishnav explains. “I really wanted to find a way to fill that gap, and contribute to the long-standing vision of creating a complete fitness landscape.”

      Martin Taylor, a professor of genetics at the University of Edinburgh’s Medical Research Council Human Genetics Unit who was not involved in the research, says the study shows that artificial intelligence can not only predict the effect of regulatory DNA changes, but also reveal the underlying principles that govern millions of years of evolution.

      Despite the fact that the model was trained on just a fraction of yeast regulatory DNA in a few growth conditions, he’s impressed that it’s capable of making such useful predictions about the evolution of gene regulation in mammals.

      “There are obvious near-term applications, such as the custom design of regulatory DNA for yeast in brewing, baking, and biotechnology,” he explains. “But extensions of this work could also help identify disease mutations in human regulatory DNA that are currently difficult to find and largely overlooked in the clinic. This work suggests there is a bright future for AI models of gene regulation trained on richer, more complex, and more diverse datasets.”

      Even before the study was formally published, Vaishnav began receiving queries from other researchers hoping to use the model to devise non-coding DNA sequences for use in gene therapies.

      “People have been studying regulatory evolution and fitness landscapes for decades now,” Vaishnav says. “I think our framework will go a long way in answering fundamental, open questions about the evolution and evolvability of gene regulatory DNA — and even help us design biological sequences for exciting new applications.” More