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    Using generative AI to improve software testing

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    Generative AI is getting plenty of attention for its ability to create text and images. But those media represent only a fraction of the data that proliferate in our society today. Data are generated every time a patient goes through a medical system, a storm impacts a flight, or a person interacts with a software application.

    Using generative AI to create realistic synthetic data around those scenarios can help organizations more effectively treat patients, reroute planes, or improve software platforms — especially in scenarios where real-world data are limited or sensitive.

    For the last three years, the MIT spinout DataCebo has offered a generative software system called the Synthetic Data Vault to help organizations create synthetic data to do things like test software applications and train machine learning models.

    The Synthetic Data Vault, or SDV, has been downloaded more than 1 million times, with more than 10,000 data scientists using the open-source library for generating synthetic tabular data. The founders — Principal Research Scientist Kalyan Veeramachaneni and alumna Neha Patki ’15, SM ’16 — believe the company’s success is due to SDV’s ability to revolutionize software testing.

    SDV goes viral

    In 2016, Veeramachaneni’s group in the Data to AI Lab unveiled a suite of open-source generative AI tools to help organizations create synthetic data that matched the statistical properties of real data.

    Companies can use synthetic data instead of sensitive information in programs while still preserving the statistical relationships between datapoints. Companies can also use synthetic data to run new software through simulations to see how it performs before releasing it to the public.

    Veeramachaneni’s group came across the problem because it was working with companies that wanted to share their data for research.

    “MIT helps you see all these different use cases,” Patki explains. “You work with finance companies and health care companies, and all those projects are useful to formulate solutions across industries.”

    In 2020, the researchers founded DataCebo to build more SDV features for larger organizations. Since then, the use cases have been as impressive as they’ve been varied.

    With DataCebo’s new flight simulator, for instance, airlines can plan for rare weather events in a way that would be impossible using only historic data. In another application, SDV users synthesized medical records to predict health outcomes for patients with cystic fibrosis. A team from Norway recently used SDV to create synthetic student data to evaluate whether various admissions policies were meritocratic and free from bias.

    In 2021, the data science platform Kaggle hosted a competition for data scientists that used SDV to create synthetic data sets to avoid using proprietary data. Roughly 30,000 data scientists participated, building solutions and predicting outcomes based on the company’s realistic data.

    And as DataCebo has grown, it’s stayed true to its MIT roots: All of the company’s current employees are MIT alumni.

    Supercharging software testing

    Although their open-source tools are being used for a variety of use cases, the company is focused on growing its traction in software testing.

    “You need data to test these software applications,” Veeramachaneni says. “Traditionally, developers manually write scripts to create synthetic data. With generative models, created using SDV, you can learn from a sample of data collected and then sample a large volume of synthetic data (which has the same properties as real data), or create specific scenarios and edge cases, and use the data to test your application.”

    For example, if a bank wanted to test a program designed to reject transfers from accounts with no money in them, it would have to simulate many accounts simultaneously transacting. Doing that with data created manually would take a lot of time. With DataCebo’s generative models, customers can create any edge case they want to test.

    “It’s common for industries to have data that is sensitive in some capacity,” Patki says. “Often when you’re in a domain with sensitive data you’re dealing with regulations, and even if there aren’t legal regulations, it’s in companies’ best interest to be diligent about who gets access to what at which time. So, synthetic data is always better from a privacy perspective.”

    Scaling synthetic data

    Veeramachaneni believes DataCebo is advancing the field of what it calls synthetic enterprise data, or data generated from user behavior on large companies’ software applications.

    “Enterprise data of this kind is complex, and there is no universal availability of it, unlike language data,” Veeramachaneni says. “When folks use our publicly available software and report back if works on a certain pattern, we learn a lot of these unique patterns, and it allows us to improve our algorithms. From one perspective, we are building a corpus of these complex patterns, which for language and images is readily available. “

    DataCebo also recently released features to improve SDV’s usefulness, including tools to assess the “realism” of the generated data, called the SDMetrics library as well as a way to compare models’ performances called SDGym.

    “It’s about ensuring organizations trust this new data,” Veeramachaneni says. “[Our tools offer] programmable synthetic data, which means we allow enterprises to insert their specific insight and intuition to build more transparent models.”

    As companies in every industry rush to adopt AI and other data science tools, DataCebo is ultimately helping them do so in a way that is more transparent and responsible.

    “In the next few years, synthetic data from generative models will transform all data work,” Veeramachaneni says. “We believe 90 percent of enterprise operations can be done with synthetic data.” More

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      Dealing with the limitations of our noisy world

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      Tamara Broderick first set foot on MIT’s campus when she was a high school student, as a participant in the inaugural Women’s Technology Program. The monthlong summer academic experience gives young women a hands-on introduction to engineering and computer science.

      What is the probability that she would return to MIT years later, this time as a faculty member?

      That’s a question Broderick could probably answer quantitatively using Bayesian inference, a statistical approach to probability that tries to quantify uncertainty by continuously updating one’s assumptions as new data are obtained.

      In her lab at MIT, the newly tenured associate professor in the Department of Electrical Engineering and Computer Science (EECS) uses Bayesian inference to quantify uncertainty and measure the robustness of data analysis techniques.

      “I’ve always been really interested in understanding not just ‘What do we know from data analysis,’ but ‘How well do we know it?’” says Broderick, who is also a member of the Laboratory for Information and Decision Systems and the Institute for Data, Systems, and Society. “The reality is that we live in a noisy world, and we can’t always get exactly the data that we want. How do we learn from data but at the same time recognize that there are limitations and deal appropriately with them?”

      Broadly, her focus is on helping people understand the confines of the statistical tools available to them and, sometimes, working with them to craft better tools for a particular situation.

      For instance, her group recently collaborated with oceanographers to develop a machine-learning model that can make more accurate predictions about ocean currents. In another project, she and others worked with degenerative disease specialists on a tool that helps severely motor-impaired individuals utilize a computer’s graphical user interface by manipulating a single switch.

      A common thread woven through her work is an emphasis on collaboration.

      “Working in data analysis, you get to hang out in everybody’s backyard, so to speak. You really can’t get bored because you can always be learning about some other field and thinking about how we can apply machine learning there,” she says.

      Hanging out in many academic “backyards” is especially appealing to Broderick, who struggled even from a young age to narrow down her interests.

      A math mindset

      Growing up in a suburb of Cleveland, Ohio, Broderick had an interest in math for as long as she can remember. She recalls being fascinated by the idea of what would happen if you kept adding a number to itself, starting with 1+1=2 and then 2+2=4.

      “I was maybe 5 years old, so I didn’t know what ‘powers of two’ were or anything like that. I was just really into math,” she says.

      Her father recognized her interest in the subject and enrolled her in a Johns Hopkins program called the Center for Talented Youth, which gave Broderick the opportunity to take three-week summer classes on a range of subjects, from astronomy to number theory to computer science.

      Later, in high school, she conducted astrophysics research with a postdoc at Case Western University. In the summer of 2002, she spent four weeks at MIT as a member of the first class of the Women’s Technology Program.

      She especially enjoyed the freedom offered by the program, and its focus on using intuition and ingenuity to achieve high-level goals. For instance, the cohort was tasked with building a device with LEGOs that they could use to biopsy a grape suspended in Jell-O.

      The program showed her how much creativity is involved in engineering and computer science, and piqued her interest in pursuing an academic career.

      “But when I got into college at Princeton, I could not decide — math, physics, computer science — they all seemed super-cool. I wanted to do all of it,” she says.

      She settled on pursuing an undergraduate math degree but took all the physics and computer science courses she could cram into her schedule.

      Digging into data analysis

      After receiving a Marshall Scholarship, Broderick spent two years at Cambridge University in the United Kingdom, earning a master of advanced study in mathematics and a master of philosophy in physics.

      In the UK, she took a number of statistics and data analysis classes, including her first class on Bayesian data analysis in the field of machine learning.

      It was a transformative experience, she recalls.

      “During my time in the U.K., I realized that I really like solving real-world problems that matter to people, and Bayesian inference was being used in some of the most important problems out there,” she says.

      Back in the U.S., Broderick headed to the University of California at Berkeley, where she joined the lab of Professor Michael I. Jordan as a grad student. She earned a PhD in statistics with a focus on Bayesian data analysis. 

      She decided to pursue a career in academia and was drawn to MIT by the collaborative nature of the EECS department and by how passionate and friendly her would-be colleagues were.

      Her first impressions panned out, and Broderick says she has found a community at MIT that helps her be creative and explore hard, impactful problems with wide-ranging applications.

      “I’ve been lucky to work with a really amazing set of students and postdocs in my lab — brilliant and hard-working people whose hearts are in the right place,” she says.

      One of her team’s recent projects involves a collaboration with an economist who studies the use of microcredit, or the lending of small amounts of money at very low interest rates, in impoverished areas.

      The goal of microcredit programs is to raise people out of poverty. Economists run randomized control trials of villages in a region that receive or don’t receive microcredit. They want to generalize the study results, predicting the expected outcome if one applies microcredit to other villages outside of their study.

      But Broderick and her collaborators have found that results of some microcredit studies can be very brittle. Removing one or a few data points from the dataset can completely change the results. One issue is that researchers often use empirical averages, where a few very high or low data points can skew the results.

      Using machine learning, she and her collaborators developed a method that can determine how many data points must be dropped to change the substantive conclusion of the study. With their tool, a scientist can see how brittle the results are.

      “Sometimes dropping a very small fraction of data can change the major results of a data analysis, and then we might worry how far those conclusions generalize to new scenarios. Are there ways we can flag that for people? That is what we are getting at with this work,” she explains.

      At the same time, she is continuing to collaborate with researchers in a range of fields, such as genetics, to understand the pros and cons of different machine-learning techniques and other data analysis tools.

      Happy trails

      Exploration is what drives Broderick as a researcher, and it also fuels one of her passions outside the lab. She and her husband enjoy collecting patches they earn by hiking all the trails in a park or trail system.

      “I think my hobby really combines my interests of being outdoors and spreadsheets,” she says. “With these hiking patches, you have to explore everything and then you see areas you wouldn’t normally see. It is adventurous, in that way.”

      They’ve discovered some amazing hikes they would never have known about, but also embarked on more than a few “total disaster hikes,” she says. But each hike, whether a hidden gem or an overgrown mess, offers its own rewards.

      And just like in her research, curiosity, open-mindedness, and a passion for problem-solving have never led her astray. More

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      New AI model could streamline operations in a robotic warehouse

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      Hundreds of robots zip back and forth across the floor of a colossal robotic warehouse, grabbing items and delivering them to human workers for packing and shipping. Such warehouses are increasingly becoming part of the supply chain in many industries, from e-commerce to automotive production.

      However, getting 800 robots to and from their destinations efficiently while keeping them from crashing into each other is no easy task. It is such a complex problem that even the best path-finding algorithms struggle to keep up with the breakneck pace of e-commerce or manufacturing. 

      In a sense, these robots are like cars trying to navigate a crowded city center. So, a group of MIT researchers who use AI to mitigate traffic congestion applied ideas from that domain to tackle this problem.

      They built a deep-learning model that encodes important information about the warehouse, including the robots, planned paths, tasks, and obstacles, and uses it to predict the best areas of the warehouse to decongest to improve overall efficiency.

      Their technique divides the warehouse robots into groups, so these smaller groups of robots can be decongested faster with traditional algorithms used to coordinate robots. In the end, their method decongests the robots nearly four times faster than a strong random search method.

      In addition to streamlining warehouse operations, this deep learning approach could be used in other complex planning tasks, like computer chip design or pipe routing in large buildings.

      “We devised a new neural network architecture that is actually suitable for real-time operations at the scale and complexity of these warehouses. It can encode hundreds of robots in terms of their trajectories, origins, destinations, and relationships with other robots, and it can do this in an efficient manner that reuses computation across groups of robots,” says Cathy Wu, the Gilbert W. Winslow Career Development Assistant Professor in Civil and Environmental Engineering (CEE), and a member of a member of the Laboratory for Information and Decision Systems (LIDS) and the Institute for Data, Systems, and Society (IDSS).

      Wu, senior author of a paper on this technique, is joined by lead author Zhongxia Yan, a graduate student in electrical engineering and computer science. The work will be presented at the International Conference on Learning Representations.

      Robotic Tetris

      From a bird’s eye view, the floor of a robotic e-commerce warehouse looks a bit like a fast-paced game of “Tetris.”

      When a customer order comes in, a robot travels to an area of the warehouse, grabs the shelf that holds the requested item, and delivers it to a human operator who picks and packs the item. Hundreds of robots do this simultaneously, and if two robots’ paths conflict as they cross the massive warehouse, they might crash.

      Traditional search-based algorithms avoid potential crashes by keeping one robot on its course and replanning a trajectory for the other. But with so many robots and potential collisions, the problem quickly grows exponentially.

      “Because the warehouse is operating online, the robots are replanned about every 100 milliseconds. That means that every second, a robot is replanned 10 times. So, these operations need to be very fast,” Wu says.

      Because time is so critical during replanning, the MIT researchers use machine learning to focus the replanning on the most actionable areas of congestion — where there exists the most potential to reduce the total travel time of robots.

      Wu and Yan built a neural network architecture that considers smaller groups of robots at the same time. For instance, in a warehouse with 800 robots, the network might cut the warehouse floor into smaller groups that contain 40 robots each.

      Then, it predicts which group has the most potential to improve the overall solution if a search-based solver were used to coordinate trajectories of robots in that group.

      An iterative process, the overall algorithm picks the most promising robot group with the neural network, decongests the group with the search-based solver, then picks the next most promising group with the neural network, and so on.

      Considering relationships

      The neural network can reason about groups of robots efficiently because it captures complicated relationships that exist between individual robots. For example, even though one robot may be far away from another initially, their paths could still cross during their trips.

      The technique also streamlines computation by encoding constraints only once, rather than repeating the process for each subproblem. For instance, in a warehouse with 800 robots, decongesting a group of 40 robots requires holding the other 760 robots as constraints. Other approaches require reasoning about all 800 robots once per group in each iteration.

      Instead, the researchers’ approach only requires reasoning about the 800 robots once across all groups in each iteration.

      “The warehouse is one big setting, so a lot of these robot groups will have some shared aspects of the larger problem. We designed our architecture to make use of this common information,” she adds.

      They tested their technique in several simulated environments, including some set up like warehouses, some with random obstacles, and even maze-like settings that emulate building interiors.

      By identifying more effective groups to decongest, their learning-based approach decongests the warehouse up to four times faster than strong, non-learning-based approaches. Even when they factored in the additional computational overhead of running the neural network, their approach still solved the problem 3.5 times faster.

      In the future, the researchers want to derive simple, rule-based insights from their neural model, since the decisions of the neural network can be opaque and difficult to interpret. Simpler, rule-based methods could also be easier to implement and maintain in actual robotic warehouse settings.

      “This approach is based on a novel architecture where convolution and attention mechanisms interact effectively and efficiently. Impressively, this leads to being able to take into account the spatiotemporal component of the constructed paths without the need of problem-specific feature engineering. The results are outstanding: Not only is it possible to improve on state-of-the-art large neighborhood search methods in terms of quality of the solution and speed, but the model generalizes to unseen cases wonderfully,” says Andrea Lodi, the Andrew H. and Ann R. Tisch Professor at Cornell Tech, and who was not involved with this research.

      This work was supported by Amazon and the MIT Amazon Science Hub. More

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      Automated method helps researchers quantify uncertainty in their predictions

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      Pollsters trying to predict presidential election results and physicists searching for distant exoplanets have at least one thing in common: They often use a tried-and-true scientific technique called Bayesian inference.

      Bayesian inference allows these scientists to effectively estimate some unknown parameter — like the winner of an election — from data such as poll results. But Bayesian inference can be slow, sometimes consuming weeks or even months of computation time or requiring a researcher to spend hours deriving tedious equations by hand. 

      Researchers from MIT and elsewhere have introduced an optimization technique that speeds things up without requiring a scientist to do a lot of additional work. Their method can achieve more accurate results faster than another popular approach for accelerating Bayesian inference.

      Using this new automated technique, a scientist could simply input their model and then the optimization method does all the calculations under the hood to provide an approximation of some unknown parameter. The method also offers reliable uncertainty estimates that can help a researcher understand when to trust its predictions.

      This versatile technique could be applied to a wide array of scientific quandaries that incorporate Bayesian inference. For instance, it could be used by economists studying the impact of microcredit loans in developing nations or sports analysts using a model to rank top tennis players.

      “When you actually dig into what people are doing in the social sciences, physics, chemistry, or biology, they are often using a lot of the same tools under the hood. There are so many Bayesian analyses out there. If we can build a really great tool that makes these researchers lives easier, then we can really make a difference to a lot of people in many different research areas,” says senior author Tamara Broderick, an associate professor in MIT’s Department of Electrical Engineering and Computer Science (EECS) and a member of the Laboratory for Information and Decision Systems and the Institute for Data, Systems, and Society.

      Broderick is joined on the paper by co-lead authors Ryan Giordano, an assistant professor of statistics at the University of California at Berkeley; and Martin Ingram, a data scientist at the AI company KONUX. The paper was recently published in the Journal of Machine Learning Research.

      Faster results

      When researchers seek a faster form of Bayesian inference, they often turn to a technique called automatic differentiation variational inference (ADVI), which is often both fast to run and easy to use.

      But Broderick and her collaborators have found a number of practical issues with ADVI. It has to solve an optimization problem and can do so only approximately. So, ADVI can still require a lot of computation time and user effort to determine whether the approximate solution is good enough. And once it arrives at a solution, it tends to provide poor uncertainty estimates.

      Rather than reinventing the wheel, the team took many ideas from ADVI but turned them around to create a technique called deterministic ADVI (DADVI) that doesn’t have these downsides.

      With DADVI, it is very clear when the optimization is finished, so a user won’t need to spend extra computation time to ensure that the best solution has been found. DADVI also permits the incorporation of more powerful optimization methods that give it an additional speed and performance boost.

      Once it reaches a result, DADVI is set up to allow the use of uncertainty corrections. These corrections make its uncertainty estimates much more accurate than those of ADVI.

      DADVI also enables the user to clearly see how much error they have incurred in the approximation to the optimization problem. This prevents a user from needlessly running the optimization again and again with more and more resources to try and reduce the error.

      “We wanted to see if we could live up to the promise of black-box inference in the sense of, once the user makes their model, they can just run Bayesian inference and don’t have to derive everything by hand, they don’t need to figure out when to stop their algorithm, and they have a sense of how accurate their approximate solution is,” Broderick says.

      Defying conventional wisdom

      DADVI can be more effective than ADVI because it uses an efficient approximation method, called sample average approximation, which estimates an unknown quantity by taking a series of exact steps.

      Because the steps along the way are exact, it is clear when the objective has been reached. Plus, getting to that objective typically requires fewer steps.

      Often, researchers expect sample average approximation to be more computationally intensive than a more popular method, known as stochastic gradient, which is used by ADVI. But Broderick and her collaborators showed that, in many applications, this is not the case.

      “A lot of problems really do have special structure, and you can be so much more efficient and get better performance by taking advantage of that special structure. That is something we have really seen in this paper,” she adds.

      They tested DADVI on a number of real-world models and datasets, including a model used by economists to evaluate the effectiveness of microcredit loans and one used in ecology to determine whether a species is present at a particular site.

      Across the board, they found that DADVI can estimate unknown parameters faster and more reliably than other methods, and achieves as good or better accuracy than ADVI. Because it is easier to use than other techniques, DADVI could offer a boost to scientists in a wide variety of fields.

      In the future, the researchers want to dig deeper into correction methods for uncertainty estimates so they can better understand why these corrections can produce such accurate uncertainties, and when they could fall short.

      “In applied statistics, we often have to use approximate algorithms for problems that are too complex or high-dimensional to allow exact solutions to be computed in reasonable time. This new paper offers an interesting set of theory and empirical results that point to an improvement in a popular existing approximate algorithm for Bayesian inference,” says Andrew Gelman ’85, ’86, a professor of statistics and political science at Columbia University, who was not involved with the study. “As one of the team involved in the creation of that earlier work, I’m happy to see our algorithm superseded by something more stable.”

      This research was supported by a National Science Foundation CAREER Award and the U.S. Office of Naval Research.  More

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      AI accelerates problem-solving in complex scenarios

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      While Santa Claus may have a magical sleigh and nine plucky reindeer to help him deliver presents, for companies like FedEx, the optimization problem of efficiently routing holiday packages is so complicated that they often employ specialized software to find a solution.

      This software, called a mixed-integer linear programming (MILP) solver, splits a massive optimization problem into smaller pieces and uses generic algorithms to try and find the best solution. However, the solver could take hours — or even days — to arrive at a solution.

      The process is so onerous that a company often must stop the software partway through, accepting a solution that is not ideal but the best that could be generated in a set amount of time.

      Researchers from MIT and ETH Zurich used machine learning to speed things up.

      They identified a key intermediate step in MILP solvers that has so many potential solutions it takes an enormous amount of time to unravel, which slows the entire process. The researchers employed a filtering technique to simplify this step, then used machine learning to find the optimal solution for a specific type of problem.

      Their data-driven approach enables a company to use its own data to tailor a general-purpose MILP solver to the problem at hand.

      This new technique sped up MILP solvers between 30 and 70 percent, without any drop in accuracy. One could use this method to obtain an optimal solution more quickly or, for especially complex problems, a better solution in a tractable amount of time.

      This approach could be used wherever MILP solvers are employed, such as by ride-hailing services, electric grid operators, vaccination distributors, or any entity faced with a thorny resource-allocation problem.

      “Sometimes, in a field like optimization, it is very common for folks to think of solutions as either purely machine learning or purely classical. I am a firm believer that we want to get the best of both worlds, and this is a really strong instantiation of that hybrid approach,” says senior author Cathy Wu, the Gilbert W. Winslow Career Development Assistant Professor in Civil and Environmental Engineering (CEE), and a member of a member of the Laboratory for Information and Decision Systems (LIDS) and the Institute for Data, Systems, and Society (IDSS).

      Wu wrote the paper with co-lead authors Siriu Li, an IDSS graduate student, and Wenbin Ouyang, a CEE graduate student; as well as Max Paulus, a graduate student at ETH Zurich. The research will be presented at the Conference on Neural Information Processing Systems.

      Tough to solve

      MILP problems have an exponential number of potential solutions. For instance, say a traveling salesperson wants to find the shortest path to visit several cities and then return to their city of origin. If there are many cities which could be visited in any order, the number of potential solutions might be greater than the number of atoms in the universe.  

      “These problems are called NP-hard, which means it is very unlikely there is an efficient algorithm to solve them. When the problem is big enough, we can only hope to achieve some suboptimal performance,” Wu explains.

      An MILP solver employs an array of techniques and practical tricks that can achieve reasonable solutions in a tractable amount of time.

      A typical solver uses a divide-and-conquer approach, first splitting the space of potential solutions into smaller pieces with a technique called branching. Then, the solver employs a technique called cutting to tighten up these smaller pieces so they can be searched faster.

      Cutting uses a set of rules that tighten the search space without removing any feasible solutions. These rules are generated by a few dozen algorithms, known as separators, that have been created for different kinds of MILP problems. 

      Wu and her team found that the process of identifying the ideal combination of separator algorithms to use is, in itself, a problem with an exponential number of solutions.

      “Separator management is a core part of every solver, but this is an underappreciated aspect of the problem space. One of the contributions of this work is identifying the problem of separator management as a machine learning task to begin with,” she says.

      Shrinking the solution space

      She and her collaborators devised a filtering mechanism that reduces this separator search space from more than 130,000 potential combinations to around 20 options. This filtering mechanism draws on the principle of diminishing marginal returns, which says that the most benefit would come from a small set of algorithms, and adding additional algorithms won’t bring much extra improvement.

      Then they use a machine-learning model to pick the best combination of algorithms from among the 20 remaining options.

      This model is trained with a dataset specific to the user’s optimization problem, so it learns to choose algorithms that best suit the user’s particular task. Since a company like FedEx has solved routing problems many times before, using real data gleaned from past experience should lead to better solutions than starting from scratch each time.

      The model’s iterative learning process, known as contextual bandits, a form of reinforcement learning, involves picking a potential solution, getting feedback on how good it was, and then trying again to find a better solution.

      This data-driven approach accelerated MILP solvers between 30 and 70 percent without any drop in accuracy. Moreover, the speedup was similar when they applied it to a simpler, open-source solver and a more powerful, commercial solver.

      In the future, Wu and her collaborators want to apply this approach to even more complex MILP problems, where gathering labeled data to train the model could be especially challenging. Perhaps they can train the model on a smaller dataset and then tweak it to tackle a much larger optimization problem, she says. The researchers are also interested in interpreting the learned model to better understand the effectiveness of different separator algorithms.

      This research is supported, in part, by Mathworks, the National Science Foundation (NSF), the MIT Amazon Science Hub, and MIT’s Research Support Committee. More

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      A more effective experimental design for engineering a cell into a new state

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      A strategy for cellular reprogramming involves using targeted genetic interventions to engineer a cell into a new state. The technique holds great promise in immunotherapy, for instance, where researchers could reprogram a patient’s T-cells so they are more potent cancer killers. Someday, the approach could also help identify life-saving cancer treatments or regenerative therapies that repair disease-ravaged organs.

      But the human body has about 20,000 genes, and a genetic perturbation could be on a combination of genes or on any of the over 1,000 transcription factors that regulate the genes. Because the search space is vast and genetic experiments are costly, scientists often struggle to find the ideal perturbation for their particular application.   

      Researchers from MIT and Harvard University developed a new, computational approach that can efficiently identify optimal genetic perturbations based on a much smaller number of experiments than traditional methods.

      Their algorithmic technique leverages the cause-and-effect relationship between factors in a complex system, such as genome regulation, to prioritize the best intervention in each round of sequential experiments.

      The researchers conducted a rigorous theoretical analysis to determine that their technique did, indeed, identify optimal interventions. With that theoretical framework in place, they applied the algorithms to real biological data designed to mimic a cellular reprogramming experiment. Their algorithms were the most efficient and effective.

      “Too often, large-scale experiments are designed empirically. A careful causal framework for sequential experimentation may allow identifying optimal interventions with fewer trials, thereby reducing experimental costs,” says co-senior author Caroline Uhler, a professor in the Department of Electrical Engineering and Computer Science (EECS) who is also co-director of the Eric and Wendy Schmidt Center at the Broad Institute of MIT and Harvard, and a researcher at MIT’s Laboratory for Information and Decision Systems (LIDS) and Institute for Data, Systems and Society (IDSS).

      Joining Uhler on the paper, which appears today in Nature Machine Intelligence, are lead author Jiaqi Zhang, a graduate student and Eric and Wendy Schmidt Center Fellow; co-senior author Themistoklis P. Sapsis, professor of mechanical and ocean engineering at MIT and a member of IDSS; and others at Harvard and MIT.

      Active learning

      When scientists try to design an effective intervention for a complex system, like in cellular reprogramming, they often perform experiments sequentially. Such settings are ideally suited for the use of a machine-learning approach called active learning. Data samples are collected and used to learn a model of the system that incorporates the knowledge gathered so far. From this model, an acquisition function is designed — an equation that evaluates all potential interventions and picks the best one to test in the next trial.

      This process is repeated until an optimal intervention is identified (or resources to fund subsequent experiments run out).

      “While there are several generic acquisition functions to sequentially design experiments, these are not effective for problems of such complexity, leading to very slow convergence,” Sapsis explains.

      Acquisition functions typically consider correlation between factors, such as which genes are co-expressed. But focusing only on correlation ignores the regulatory relationships or causal structure of the system. For instance, a genetic intervention can only affect the expression of downstream genes, but a correlation-based approach would not be able to distinguish between genes that are upstream or downstream.

      “You can learn some of this causal knowledge from the data and use that to design an intervention more efficiently,” Zhang explains.

      The MIT and Harvard researchers leveraged this underlying causal structure for their technique. First, they carefully constructed an algorithm so it can only learn models of the system that account for causal relationships.

      Then the researchers designed the acquisition function so it automatically evaluates interventions using information on these causal relationships. They crafted this function so it prioritizes the most informative interventions, meaning those most likely to lead to the optimal intervention in subsequent experiments.

      “By considering causal models instead of correlation-based models, we can already rule out certain interventions. Then, whenever you get new data, you can learn a more accurate causal model and thereby further shrink the space of interventions,” Uhler explains.

      This smaller search space, coupled with the acquisition function’s special focus on the most informative interventions, is what makes their approach so efficient.

      The researchers further improved their acquisition function using a technique known as output weighting, inspired by the study of extreme events in complex systems. This method carefully emphasizes interventions that are likely to be closer to the optimal intervention.

      “Essentially, we view an optimal intervention as an ‘extreme event’ within the space of all possible, suboptimal interventions and use some of the ideas we have developed for these problems,” Sapsis says.    

      Enhanced efficiency

      They tested their algorithms using real biological data in a simulated cellular reprogramming experiment. For this test, they sought a genetic perturbation that would result in a desired shift in average gene expression. Their acquisition functions consistently identified better interventions than baseline methods through every step in the multi-stage experiment.

      “If you cut the experiment off at any stage, ours would still be more efficient than the baselines. This means you could run fewer experiments and get the same or better results,” Zhang says.

      The researchers are currently working with experimentalists to apply their technique toward cellular reprogramming in the lab.

      Their approach could also be applied to problems outside genomics, such as identifying optimal prices for consumer products or enabling optimal feedback control in fluid mechanics applications.

      In the future, they plan to enhance their technique for optimizations beyond those that seek to match a desired mean. In addition, their method assumes that scientists already understand the causal relationships in their system, but future work could explore how to use AI to learn that information, as well.

      This work was funded, in part, by the Office of Naval Research, the MIT-IBM Watson AI Lab, the MIT J-Clinic for Machine Learning and Health, the Eric and Wendy Schmidt Center at the Broad Institute, a Simons Investigator Award, the Air Force Office of Scientific Research, and a National Science Foundation Graduate Fellowship. More

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      Artificial intelligence for augmentation and productivity

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      The MIT Stephen A. Schwarzman College of Computing has awarded seed grants to seven projects that are exploring how artificial intelligence and human-computer interaction can be leveraged to enhance modern work spaces to achieve better management and higher productivity.

      Funded by Andrew W. Houston ’05 and Dropbox Inc., the projects are intended to be interdisciplinary and bring together researchers from computing, social sciences, and management.

      The seed grants can enable the project teams to conduct research that leads to bigger endeavors in this rapidly evolving area, as well as build community around questions related to AI-augmented management.

      The seven selected projects and research leads include:

      “LLMex: Implementing Vannevar Bush’s Vision of the Memex Using Large Language Models,” led by Patti Maes of the Media Lab and David Karger of the Department of Electrical Engineering and Computer Science (EECS) and the Computer Science and Artificial Intelligence Laboratory (CSAIL). Inspired by Vannevar Bush’s Memex, this project proposes to design, implement, and test the concept of memory prosthetics using large language models (LLMs). The AI-based system will intelligently help an individual keep track of vast amounts of information, accelerate productivity, and reduce errors by automatically recording their work actions and meetings, supporting retrieval based on metadata and vague descriptions, and suggesting relevant, personalized information proactively based on the user’s current focus and context.

      “Using AI Agents to Simulate Social Scenarios,” led by John Horton of the MIT Sloan School of Management and Jacob Andreas of EECS and CSAIL. This project imagines the ability to easily simulate policies, organizational arrangements, and communication tools with AI agents before implementation. Tapping into the capabilities of modern LLMs to serve as a computational model of humans makes this vision of social simulation more realistic, and potentially more predictive.

      “Human Expertise in the Age of AI: Can We Have Our Cake and Eat it Too?” led by Manish Raghavan of MIT Sloan and EECS, and Devavrat Shah of EECS and the Laboratory for Information and Decision Systems. Progress in machine learning, AI, and in algorithmic decision aids has raised the prospect that algorithms may complement human decision-making in a wide variety of settings. Rather than replacing human professionals, this project sees a future where AI and algorithmic decision aids play a role that is complementary to human expertise.

      “Implementing Generative AI in U.S. Hospitals,” led by Julie Shah of the Department of Aeronautics and Astronautics and CSAIL, Retsef Levi of MIT Sloan and the Operations Research Center, Kate Kellog of MIT Sloan, and Ben Armstrong of the Industrial Performance Center. In recent years, studies have linked a rise in burnout from doctors and nurses in the United States with increased administrative burdens associated with electronic health records and other technologies. This project aims to develop a holistic framework to study how generative AI technologies can both increase productivity for organizations and improve job quality for workers in health care settings.

      “Generative AI Augmented Software Tools to Democratize Programming,” led by Harold Abelson of EECS and CSAIL, Cynthia Breazeal of the Media Lab, and Eric Klopfer of the Comparative Media Studies/Writing. Progress in generative AI over the past year is fomenting an upheaval in assumptions about future careers in software and deprecating the role of coding. This project will stimulate a similar transformation in computing education for those who have no prior technical training by creating a software tool that could eliminate much of the need for learners to deal with code when creating applications.

      “Acquiring Expertise and Societal Productivity in a World of Artificial Intelligence,” led by David Atkin and Martin Beraja of the Department of Economics, and Danielle Li of MIT Sloan. Generative AI is thought to augment the capabilities of workers performing cognitive tasks. This project seeks to better understand how the arrival of AI technologies may impact skill acquisition and productivity, and to explore complementary policy interventions that will allow society to maximize the gains from such technologies.

      “AI Augmented Onboarding and Support,” led by Tim Kraska of EECS and CSAIL, and Christoph Paus of the Department of Physics. While LLMs have made enormous leaps forward in recent years and are poised to fundamentally change the way students and professionals learn about new tools and systems, there is often a steep learning curve which people have to climb in order to make full use of the resource. To help mitigate the issue, this project proposes the development of new LLM-powered onboarding and support systems that will positively impact the way support teams operate and improve the user experience. More

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      The tenured engineers of 2023

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      In 2023, MIT granted tenure to nine faculty members across the School of Engineering. This year’s tenured engineers hold appointments in the departments of Biological Engineering, Civil and Environmental Engineering, Electrical Engineering and Computer Science (which reports jointly to the School of Engineering and MIT Schwarzman College of Computing), Materials Science and Engineering, and Mechanical Engineering, as well as the Institute for Medical Engineering and Science (IMES).

      “I am truly inspired by this remarkable group of talented faculty members,” says Anantha Chandrakasan, dean of the School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “The work they are doing, both in the lab and in the classroom, has made a tremendous impact at MIT and in the wider world. Their important research has applications in a diverse range of fields and industries. I am thrilled to congratulate them on the milestone of receiving tenure.”

      This year’s newly tenured engineering faculty include:

      Michael Birnbaum, Class of 1956 Career Development Professor, associate professor of biological engineering, and faculty member at the Koch Institute for Integrative Cancer Research at MIT, works on understanding and manipulating immune recognition in cancer and infections. By using a variety of techniques to study the antigen recognition of T cells, he and his team aim to develop the next generation of immunotherapies.  
      Tamara Broderick, associate professor of electrical engineering and computer science and member of the MIT Laboratory for Information and Decision Systems (LIDS) and the MIT Institute for Data, Systems, and Society (IDSS), works to provide fast and reliable quantification of uncertainty and robustness in modern data analysis procedures. Broderick and her research group develop data analysis tools with applications in fields, including genetics, economics, and assistive technology. 
      Tal Cohen, associate professor of civil and environmental engineering and mechanical engineering, uses nonlinear solid mechanics to understand how materials behave under extreme conditions. By studying material instabilities, extreme dynamic loading conditions, growth, and chemical coupling, Cohen and her team combine theoretical models and experiments to shape our understanding of the observed phenomena and apply those insights in the design and characterization of material systems. 
      Betar Gallant, Class of 1922 Career Development Professor and associate professor of mechanical engineering, develops advanced materials and chemistries for next-generation lithium-ion and lithium primary batteries and electrochemical carbon dioxide mitigation technologies. Her group’s work could lead to higher-energy and more sustainable batteries for electric vehicles, longer-lasting implantable medical devices, and new methods of carbon capture and conversion. 
      Rafael Jaramillo, Thomas Lord Career Development Professor and associate professor of materials science and engineering, studies the synthesis, properties, and applications of electronic materials, particularly chalcogenide compound semiconductors. His work has applications in microelectronics, integrated photonics, telecommunications, and photovoltaics. 
      Benedetto Marelli, associate professor of civil and environmental engineering, conducts research on the synthesis, assembly, and nanomanufacturing of structural biopolymers. He and his research team develop biomaterials for applications in agriculture, food security, and food safety. 
      Ellen Roche, Latham Family Career Development Professor, an associate professor of mechanical engineering, and a core faculty of IMES, designs and develops implantable, biomimetic therapeutic devices and soft robotics that mechanically assist and repair tissue, deliver therapies, and enable enhanced preclinical testing. Her devices have a wide range of applications in human health, including cardiovascular and respiratory disease. 
      Serguei Saavedra, associate professor of civil and environmental engineering, uses systems thinking, synthesis, and mathematical modeling to study the persistence of ecological systems under changing environments. His theoretical research is used to develop hypotheses and corroborate predictions of how ecological systems respond to climate change. 
      Justin Solomon, associate professor of electrical engineering and computer science and member of the MIT Computer Science and Artificial Intelligence Laboratory and MIT Center for Computational Science and Engineering, works at the intersection of geometry, large-scale optimization, computer graphics, and machine learning. His research has diverse applications in machine learning, computer graphics, and geometric data processing.  More

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      The curse of variety in transportation systems

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      Cathy Wu has always delighted in systems that run smoothly. In high school, she designed a project to optimize the best route for getting to class on time. Her research interests and career track are evidence of a propensity for organizing and optimizing, coupled with a strong sense of responsibility to contribute to society instilled by her parents at a young age.

      As an undergraduate at MIT, Wu explored domains like agriculture, energy, and education, eventually homing in on transportation. “Transportation touches each of our lives,” she says. “Every day, we experience the inefficiencies and safety issues as well as the environmental harms associated with our transportation systems. I believe we can and should do better.”

      But doing so is complicated. Consider the long-standing issue of traffic systems control. Wu explains that it is not one problem, but more accurately a family of control problems impacted by variables like time of day, weather, and vehicle type — not to mention the types of sensing and communication technologies used to measure roadway information. Every differentiating factor introduces an exponentially larger set of control problems. There are thousands of control-problem variations and hundreds, if not thousands, of studies and papers dedicated to each problem. Wu refers to the sheer number of variations as the curse of variety — and it is hindering innovation.

      Play video

      “To prove that a new control strategy can be safely deployed on our streets can take years. As time lags, we lose opportunities to improve safety and equity while mitigating environmental impacts. Accelerating this process has huge potential,” says Wu.  

      Which is why she and her group in the MIT Laboratory for Information and Decision Systems are devising machine learning-based methods to solve not just a single control problem or a single optimization problem, but families of control and optimization problems at scale. “In our case, we’re examining emerging transportation problems that people have spent decades trying to solve with classical approaches. It seems to me that we need a different approach.”

      Optimizing intersections

      Currently, Wu’s largest research endeavor is called Project Greenwave. There are many sectors that directly contribute to climate change, but transportation is responsible for the largest share of greenhouse gas emissions — 29 percent, of which 81 percent is due to land transportation. And while much of the conversation around mitigating environmental impacts related to mobility is focused on electric vehicles (EVs), electrification has its drawbacks. EV fleet turnover is time-consuming (“on the order of decades,” says Wu), and limited global access to the technology presents a significant barrier to widespread adoption.

      Wu’s research, on the other hand, addresses traffic control problems by leveraging deep reinforcement learning. Specifically, she is looking at traffic intersections — and for good reason. In the United States alone, there are more than 300,000 signalized intersections where vehicles must stop or slow down before re-accelerating. And every re-acceleration burns fossil fuels and contributes to greenhouse gas emissions.

      Highlighting the magnitude of the issue, Wu says, “We have done preliminary analysis indicating that up to 15 percent of land transportation CO2 is wasted through energy spent idling and re-accelerating at intersections.”

      To date, she and her group have modeled 30,000 different intersections across 10 major metropolitan areas in the United States. That is 30,000 different configurations, roadway topologies (e.g., grade of road or elevation), different weather conditions, and variations in travel demand and fuel mix. Each intersection and its corresponding scenarios represents a unique multi-agent control problem.

      Wu and her team are devising techniques that can solve not just one, but a whole family of problems comprised of tens of thousands of scenarios. Put simply, the idea is to coordinate the timing of vehicles so they arrive at intersections when traffic lights are green, thereby eliminating the start, stop, re-accelerate conundrum. Along the way, they are building an ecosystem of tools, datasets, and methods to enable roadway interventions and impact assessments of strategies to significantly reduce carbon-intense urban driving.

      Play video

      Their collaborator on the project is the Utah Department of Transportation, which Wu says has played an essential role, in part by sharing data and practical knowledge that she and her group otherwise would not have been able to access publicly.

      “I appreciate industry and public sector collaborations,” says Wu. “When it comes to important societal problems, one really needs grounding with practitioners. One needs to be able to hear the perspectives in the field. My interactions with practitioners expand my horizons and help ground my research. You never know when you’ll hear the perspective that is the key to the solution, or perhaps the key to understanding the problem.”

      Finding the best routes

      In a similar vein, she and her research group are tackling large coordination problems. For example, vehicle routing. “Every day, delivery trucks route more than a hundred thousand packages for the city of Boston alone,” says Wu. Accomplishing the task requires, among other things, figuring out which trucks to use, which packages to deliver, and the order in which to deliver them as efficiently as possible. If and when the trucks are electrified, they will need to be charged, adding another wrinkle to the process and further complicating route optimization.

      The vehicle routing problem, and therefore the scope of Wu’s work, extends beyond truck routing for package delivery. Ride-hailing cars may need to pick up objects as well as drop them off; and what if delivery is done by bicycle or drone? In partnership with Amazon, for example, Wu and her team addressed routing and path planning for hundreds of robots (up to 800) in their warehouses.

      Every variation requires custom heuristics that are expensive and time-consuming to develop. Again, this is really a family of problems — each one complicated, time-consuming, and currently unsolved by classical techniques — and they are all variations of a central routing problem. The curse of variety meets operations and logistics.

      By combining classical approaches with modern deep-learning methods, Wu is looking for a way to automatically identify heuristics that can effectively solve all of these vehicle routing problems. So far, her approach has proved successful.

      “We’ve contributed hybrid learning approaches that take existing solution methods for small problems and incorporate them into our learning framework to scale and accelerate that existing solver for large problems. And we’re able to do this in a way that can automatically identify heuristics for specialized variations of the vehicle routing problem.” The next step, says Wu, is applying a similar approach to multi-agent robotics problems in automated warehouses.

      Wu and her group are making big strides, in part due to their dedication to use-inspired basic research. Rather than applying known methods or science to a problem, they develop new methods, new science, to address problems. The methods she and her team employ are necessitated by societal problems with practical implications. The inspiration for the approach? None other than Louis Pasteur, who described his research style in a now-famous article titled “Pasteur’s Quadrant.” Anthrax was decimating the sheep population, and Pasteur wanted to better understand why and what could be done about it. The tools of the time could not solve the problem, so he invented a new field, microbiology, not out of curiosity but out of necessity. More