Markus Andrews

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This tiny chip can safeguard user data while enabling efficient computing on a smartphone

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Health-monitoring apps can help people manage chronic diseases or stay on track with fitness goals, using nothing more than a smartphone. However, these apps can be slow and energy-inefficient because the vast machine-learning models that power them must be shuttled between a smartphone and a central memory server.

Engineers often speed things up using hardware that reduces the need to move so much data back and forth. While these machine-learning accelerators can streamline computation, they are susceptible to attackers who can steal secret information.

To reduce this vulnerability, researchers from MIT and the MIT-IBM Watson AI Lab created a machine-learning accelerator that is resistant to the two most common types of attacks. Their chip can keep a user’s health records, financial information, or other sensitive data private while still enabling huge AI models to run efficiently on devices.

The team developed several optimizations that enable strong security while only slightly slowing the device. Moreover, the added security does not impact the accuracy of computations. This machine-learning accelerator could be particularly beneficial for demanding AI applications like augmented and virtual reality or autonomous driving.

While implementing the chip would make a device slightly more expensive and less energy-efficient, that is sometimes a worthwhile price to pay for security, says lead author Maitreyi Ashok, an electrical engineering and computer science (EECS) graduate student at MIT.

“It is important to design with security in mind from the ground up. If you are trying to add even a minimal amount of security after a system has been designed, it is prohibitively expensive. We were able to effectively balance a lot of these tradeoffs during the design phase,” says Ashok.

Her co-authors include Saurav Maji, an EECS graduate student; Xin Zhang and John Cohn of the MIT-IBM Watson AI Lab; and senior author Anantha Chandrakasan, MIT’s chief innovation and strategy officer, dean of the School of Engineering, and the Vannevar Bush Professor of EECS. The research will be presented at the IEEE Custom Integrated Circuits Conference.

Side-channel susceptibility

The researchers targeted a type of machine-learning accelerator called digital in-memory compute. A digital IMC chip performs computations inside a device’s memory, where pieces of a machine-learning model are stored after being moved over from a central server.

The entire model is too big to store on the device, but by breaking it into pieces and reusing those pieces as much as possible, IMC chips reduce the amount of data that must be moved back and forth.

But IMC chips can be susceptible to hackers. In a side-channel attack, a hacker monitors the chip’s power consumption and uses statistical techniques to reverse-engineer data as the chip computes. In a bus-probing attack, the hacker can steal bits of the model and dataset by probing the communication between the accelerator and the off-chip memory.

Digital IMC speeds computation by performing millions of operations at once, but this complexity makes it tough to prevent attacks using traditional security measures, Ashok says.

She and her collaborators took a three-pronged approach to blocking side-channel and bus-probing attacks.

First, they employed a security measure where data in the IMC are split into random pieces. For instance, a bit zero might be split into three bits that still equal zero after a logical operation. The IMC never computes with all pieces in the same operation, so a side-channel attack could never reconstruct the real information.

But for this technique to work, random bits must be added to split the data. Because digital IMC performs millions of operations at once, generating so many random bits would involve too much computing. For their chip, the researchers found a way to simplify computations, making it easier to effectively split data while eliminating the need for random bits.

Second, they prevented bus-probing attacks using a lightweight cipher that encrypts the model stored in off-chip memory. This lightweight cipher only requires simple computations. In addition, they only decrypted the pieces of the model stored on the chip when necessary.

Third, to improve security, they generated the key that decrypts the cipher directly on the chip, rather than moving it back and forth with the model. They generated this unique key from random variations in the chip that are introduced during manufacturing, using what is known as a physically unclonable function.

“Maybe one wire is going to be a little bit thicker than another. We can use these variations to get zeros and ones out of a circuit. For every chip, we can get a random key that should be consistent because these random properties shouldn’t change significantly over time,” Ashok explains.

They reused the memory cells on the chip, leveraging the imperfections in these cells to generate the key. This requires less computation than generating a key from scratch.

“As security has become a critical issue in the design of edge devices, there is a need to develop a complete system stack focusing on secure operation. This work focuses on security for machine-learning workloads and describes a digital processor that uses cross-cutting optimization. It incorporates encrypted data access between memory and processor, approaches to preventing side-channel attacks using randomization, and exploiting variability to generate unique codes. Such designs are going to be critical in future mobile devices,” says Chandrakasan.

Safety testing

To test their chip, the researchers took on the role of hackers and tried to steal secret information using side-channel and bus-probing attacks.

Even after making millions of attempts, they couldn’t reconstruct any real information or extract pieces of the model or dataset. The cipher also remained unbreakable. By contrast, it took only about 5,000 samples to steal information from an unprotected chip.

The addition of security did reduce the energy efficiency of the accelerator, and it also required a larger chip area, which would make it more expensive to fabricate.

The team is planning to explore methods that could reduce the energy consumption and size of their chip in the future, which would make it easier to implement at scale.

“As it becomes too expensive, it becomes harder to convince someone that security is critical. Future work could explore these tradeoffs. Maybe we could make it a little less secure but easier to implement and less expensive,” Ashok says.

The research is funded, in part, by the MIT-IBM Watson AI Lab, the National Science Foundation, and a Mathworks Engineering Fellowship. More

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  • 175 Shares51 Views

    in Data Management & Statistics

    This tiny chip can safeguard user data while enabling efficient computing on a smartphone

    Health-monitoring apps can help people manage chronic diseases or stay on track with fitness goals, using nothing more than a smartphone. However, these apps can be slow and energy-inefficient because the vast machine-learning models that power them must be shuttled between a smartphone and a central memory server.

    Engineers often speed things up using hardware that reduces the need to move so much data back and forth. While these machine-learning accelerators can streamline computation, they are susceptible to attackers who can steal secret information.

    To reduce this vulnerability, researchers from MIT and the MIT-IBM Watson AI Lab created a machine-learning accelerator that is resistant to the two most common types of attacks. Their chip can keep a user’s health records, financial information, or other sensitive data private while still enabling huge AI models to run efficiently on devices.

    The team developed several optimizations that enable strong security while only slightly slowing the device. Moreover, the added security does not impact the accuracy of computations. This machine-learning accelerator could be particularly beneficial for demanding AI applications like augmented and virtual reality or autonomous driving.

    While implementing the chip would make a device slightly more expensive and less energy-efficient, that is sometimes a worthwhile price to pay for security, says lead author Maitreyi Ashok, an electrical engineering and computer science (EECS) graduate student at MIT.

    “It is important to design with security in mind from the ground up. If you are trying to add even a minimal amount of security after a system has been designed, it is prohibitively expensive. We were able to effectively balance a lot of these tradeoffs during the design phase,” says Ashok.

    Her co-authors include Saurav Maji, an EECS graduate student; Xin Zhang and John Cohn of the MIT-IBM Watson AI Lab; and senior author Anantha Chandrakasan, MIT’s chief innovation and strategy officer, dean of the School of Engineering, and the Vannevar Bush Professor of EECS. The research will be presented at the IEEE Custom Integrated Circuits Conference.

    Side-channel susceptibility

    The researchers targeted a type of machine-learning accelerator called digital in-memory compute. A digital IMC chip performs computations inside a device’s memory, where pieces of a machine-learning model are stored after being moved over from a central server.

    The entire model is too big to store on the device, but by breaking it into pieces and reusing those pieces as much as possible, IMC chips reduce the amount of data that must be moved back and forth.

    But IMC chips can be susceptible to hackers. In a side-channel attack, a hacker monitors the chip’s power consumption and uses statistical techniques to reverse-engineer data as the chip computes. In a bus-probing attack, the hacker can steal bits of the model and dataset by probing the communication between the accelerator and the off-chip memory.

    Digital IMC speeds computation by performing millions of operations at once, but this complexity makes it tough to prevent attacks using traditional security measures, Ashok says.

    She and her collaborators took a three-pronged approach to blocking side-channel and bus-probing attacks.

    First, they employed a security measure where data in the IMC are split into random pieces. For instance, a bit zero might be split into three bits that still equal zero after a logical operation. The IMC never computes with all pieces in the same operation, so a side-channel attack could never reconstruct the real information.

    But for this technique to work, random bits must be added to split the data. Because digital IMC performs millions of operations at once, generating so many random bits would involve too much computing. For their chip, the researchers found a way to simplify computations, making it easier to effectively split data while eliminating the need for random bits.

    Second, they prevented bus-probing attacks using a lightweight cipher that encrypts the model stored in off-chip memory. This lightweight cipher only requires simple computations. In addition, they only decrypted the pieces of the model stored on the chip when necessary.

    Third, to improve security, they generated the key that decrypts the cipher directly on the chip, rather than moving it back and forth with the model. They generated this unique key from random variations in the chip that are introduced during manufacturing, using what is known as a physically unclonable function.

    “Maybe one wire is going to be a little bit thicker than another. We can use these variations to get zeros and ones out of a circuit. For every chip, we can get a random key that should be consistent because these random properties shouldn’t change significantly over time,” Ashok explains.

    They reused the memory cells on the chip, leveraging the imperfections in these cells to generate the key. This requires less computation than generating a key from scratch.

    “As security has become a critical issue in the design of edge devices, there is a need to develop a complete system stack focusing on secure operation. This work focuses on security for machine-learning workloads and describes a digital processor that uses cross-cutting optimization. It incorporates encrypted data access between memory and processor, approaches to preventing side-channel attacks using randomization, and exploiting variability to generate unique codes. Such designs are going to be critical in future mobile devices,” says Chandrakasan.

    Safety testing

    To test their chip, the researchers took on the role of hackers and tried to steal secret information using side-channel and bus-probing attacks.

    Even after making millions of attempts, they couldn’t reconstruct any real information or extract pieces of the model or dataset. The cipher also remained unbreakable. By contrast, it took only about 5,000 samples to steal information from an unprotected chip.

    The addition of security did reduce the energy efficiency of the accelerator, and it also required a larger chip area, which would make it more expensive to fabricate.

    The team is planning to explore methods that could reduce the energy consumption and size of their chip in the future, which would make it easier to implement at scale.

    “As it becomes too expensive, it becomes harder to convince someone that security is critical. Future work could explore these tradeoffs. Maybe we could make it a little less secure but easier to implement and less expensive,” Ashok says.

    The research is funded, in part, by the MIT-IBM Watson AI Lab, the National Science Foundation, and a Mathworks Engineering Fellowship. More

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    Using deep learning to image the Earth’s planetary boundary layer

    Although the troposphere is often thought of as the closest layer of the atmosphere to the Earth’s surface, the planetary boundary layer (PBL) — the lowest layer of the troposphere — is actually the part that most significantly influences weather near the surface. In the 2018 planetary science decadal survey, the PBL was raised as an important scientific issue that has the potential to enhance storm forecasting and improve climate projections.  

    “The PBL is where the surface interacts with the atmosphere, including exchanges of moisture and heat that help lead to severe weather and a changing climate,” says Adam Milstein, a technical staff member in Lincoln Laboratory’s Applied Space Systems Group. “The PBL is also where humans live, and the turbulent movement of aerosols throughout the PBL is important for air quality that influences human health.” 

    Although vital for studying weather and climate, important features of the PBL, such as its height, are difficult to resolve with current technology. In the past four years, Lincoln Laboratory staff have been studying the PBL, focusing on two different tasks: using machine learning to make 3D-scanned profiles of the atmosphere, and resolving the vertical structure of the atmosphere more clearly in order to better predict droughts.  

    This PBL-focused research effort builds on more than a decade of related work on fast, operational neural network algorithms developed by Lincoln Laboratory for NASA missions. These missions include the Time-Resolved Observations of Precipitation structure and storm Intensity with a Constellation of Smallsats (TROPICS) mission as well as Aqua, a satellite that collects data about Earth’s water cycle and observes variables such as ocean temperature, precipitation, and water vapor in the atmosphere. These algorithms retrieve temperature and humidity from the satellite instrument data and have been shown to significantly improve the accuracy and usable global coverage of the observations over previous approaches. For TROPICS, the algorithms help retrieve data that are used to characterize a storm’s rapidly evolving structures in near-real time, and for Aqua, it has helped increase forecasting models, drought monitoring, and fire prediction. 

    These operational algorithms for TROPICS and Aqua are based on classic “shallow” neural networks to maximize speed and simplicity, creating a one-dimensional vertical profile for each spectral measurement collected by the instrument over each location. While this approach has improved observations of the atmosphere down to the surface overall, including the PBL, laboratory staff determined that newer “deep” learning techniques that treat the atmosphere over a region of interest as a three-dimensional image are needed to improve PBL details further.

    “We hypothesized that deep learning and artificial intelligence (AI) techniques could improve on current approaches by incorporating a better statistical representation of 3D temperature and humidity imagery of the atmosphere into the solutions,” Milstein says. “But it took a while to figure out how to create the best dataset — a mix of real and simulated data; we needed to prepare to train these techniques.”

    The team collaborated with Joseph Santanello of the NASA Goddard Space Flight Center and William Blackwell, also of the Applied Space Systems Group, in a recent NASA-funded effort showing that these retrieval algorithms can improve PBL detail, including more accurate determination of the PBL height than the previous state of the art. 

    While improved knowledge of the PBL is broadly useful for increasing understanding of climate and weather, one key application is prediction of droughts. According to a Global Drought Snapshot report released last year, droughts are a pressing planetary issue that the global community needs to address. Lack of humidity near the surface, specifically at the level of the PBL, is the leading indicator of drought. While previous studies using remote-sensing techniques have examined the humidity of soil to determine drought risk, studying the atmosphere can help predict when droughts will happen.  

    In an effort funded by Lincoln Laboratory’s Climate Change Initiative, Milstein, along with laboratory staff member Michael Pieper, are working with scientists at NASA’s Jet Propulsion Laboratory (JPL) to use neural network techniques to improve drought prediction over the continental United States. While the work builds off of existing operational work JPL has done incorporating (in part) the laboratory’s operational “shallow” neural network approach for Aqua, the team believes that this work and the PBL-focused deep learning research work can be combined to further improve the accuracy of drought prediction. 

    “Lincoln Laboratory has been working with NASA for more than a decade on neural network algorithms for estimating temperature and humidity in the atmosphere from space-borne infrared and microwave instruments, including those on the Aqua spacecraft,” Milstein says. “Over that time, we have learned a lot about this problem by working with the science community, including learning about what scientific challenges remain. Our long experience working on this type of remote sensing with NASA scientists, as well as our experience with using neural network techniques, gave us a unique perspective.”

    According to Milstein, the next step for this project is to compare the deep learning results to datasets from the National Oceanic and Atmospheric Administration, NASA, and the Department of Energy collected directly in the PBL using radiosondes, a type of instrument flown on a weather balloon. “These direct measurements can be considered a kind of ‘ground truth’ to quantify the accuracy of the techniques we have developed,” Milstein says.

    This improved neural network approach holds promise to demonstrate drought prediction that can exceed the capabilities of existing indicators, Milstein says, and to be a tool that scientists can rely on for decades to come. More

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    Advancing technology for aquaculture

    According to the National Oceanic and Atmospheric Administration, aquaculture in the United States represents a $1.5 billion industry annually. Like land-based farming, shellfish aquaculture requires healthy seed production in order to maintain a sustainable industry. Aquaculture hatchery production of shellfish larvae — seeds — requires close monitoring to track mortality rates and assess health from the earliest stages of life. 

    Careful observation is necessary to inform production scheduling, determine effects of naturally occurring harmful bacteria, and ensure sustainable seed production. This is an essential step for shellfish hatcheries but is currently a time-consuming manual process prone to human error. 

    With funding from MIT’s Abdul Latif Jameel Water and Food Systems Lab (J-WAFS), MIT Sea Grant is working with Associate Professor Otto Cordero of the MIT Department of Civil and Environmental Engineering, Professor Taskin Padir and Research Scientist Mark Zolotas at the Northeastern University Institute for Experiential Robotics, and others at the Aquaculture Research Corporation (ARC), and the Cape Cod Commercial Fishermen’s Alliance, to advance technology for the aquaculture industry. Located on Cape Cod, ARC is a leading shellfish hatchery, farm, and wholesaler that plays a vital role in providing high-quality shellfish seed to local and regional growers.

    Two MIT students have joined the effort this semester, working with Robert Vincent, MIT Sea Grant’s assistant director of advisory services, through the Undergraduate Research Opportunities Program (UROP). 

    First-year student Unyime Usua and sophomore Santiago Borrego are using microscopy images of shellfish seed from ARC to train machine learning algorithms that will help automate the identification and counting process. The resulting user-friendly image recognition tool aims to aid aquaculturists in differentiating and counting healthy, unhealthy, and dead shellfish larvae, improving accuracy and reducing time and effort.

    Vincent explains that AI is a powerful tool for environmental science that enables researchers, industry, and resource managers to address challenges that have long been pinch points for accurate data collection, analysis, predictions, and streamlining processes. “Funding support from programs like J-WAFS enable us to tackle these problems head-on,” he says. 

    ARC faces challenges with manually quantifying larvae classes, an important step in their seed production process. “When larvae are in their growing stages they are constantly being sized and counted,” explains Cheryl James, ARC larval/juvenile production manager. “This process is critical to encourage optimal growth and strengthen the population.” 

    Developing an automated identification and counting system will help to improve this step in the production process with time and cost benefits. “This is not an easy task,” says Vincent, “but with the guidance of Dr. Zolotas at the Northeastern University Institute for Experiential Robotics and the work of the UROP students, we have made solid progress.” 

    The UROP program benefits both researchers and students. Involving MIT UROP students in developing these types of systems provides insights into AI applications that they might not have considered, providing opportunities to explore, learn, and apply themselves while contributing to solving real challenges.

    Borrego saw this project as an opportunity to apply what he’d learned in class 6.390 (Introduction to Machine Learning) to a real-world issue. “I was starting to form an idea of how computers can see images and extract information from them,” he says. “I wanted to keep exploring that.”

    Usua decided to pursue the project because of the direct industry impacts it could have. “I’m pretty interested in seeing how we can utilize machine learning to make people’s lives easier. We are using AI to help biologists make this counting and identification process easier.” While Usua wasn’t familiar with aquaculture before starting this project, she explains, “Just hearing about the hatcheries that Dr. Vincent was telling us about, it was unfortunate that not a lot of people know what’s going on and the problems that they’re facing.”

    On Cape Cod alone, aquaculture is an $18 million per year industry. But the Massachusetts Division of Marine Fisheries estimates that hatcheries are only able to meet 70–80 percent of seed demand annually, which impacts local growers and economies. Through this project, the partners aim to develop technology that will increase seed production, advance industry capabilities, and help understand and improve the hatchery microbiome.

    Borrego explains the initial challenge of having limited data to work with. “Starting out, we had to go through and label all of the data, but going through that process helped me learn a lot.” In true MIT fashion, he shares his takeaway from the project: “Try to get the best out of what you’re given with the data you have to work with. You’re going to have to adapt and change your strategies depending on what you have.”

    Usua describes her experience going through the research process, communicating in a team, and deciding what approaches to take. “Research is a difficult and long process, but there is a lot to gain from it because it teaches you to look for things on your own and find your own solutions to problems.”

    In addition to increasing seed production and reducing the human labor required in the hatchery process, the collaborators expect this project to contribute to cost savings and technology integration to support one of the most underserved industries in the United States. 

    Borrego and Usua both plan to continue their work for a second semester with MIT Sea Grant. Borrego is interested in learning more about how technology can be used to protect the environment and wildlife. Usua says she hopes to explore more projects related to aquaculture. “It seems like there’s an infinite amount of ways to tackle these issues.” More

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    Growing our donated organ supply

    For those in need of one, an organ transplant is a matter of life and death. 

    Every year, the medical procedure gives thousands of people with advanced or end-stage diseases extended life. This “second chance” is heavily dependent on the availability, compatibility, and proximity of a precious resource that can’t be simply bought, grown, or manufactured — at least not yet.

    Instead, organs must be given — cut from one body and implanted into another. And because living organ donation is only viable in certain cases, many organs are only available for donation after the donor’s death.

    Unsurprisingly, the logistical and ethical complexity of distributing a limited number of transplant organs to a growing wait list of patients has received much attention. There’s an important part of the process that has received less focus, however, and which may hold significant untapped potential: organ procurement itself.

    “If you have a donated organ, who should you give it to? This question has been extensively studied in operations research, economics, and even applied computer science,” says Hammaad Adam, a graduate student in the Social and Engineering Systems (SES) doctoral program at the MIT Institute for Data, Systems, and Society (IDSS). “But there’s been a lot less research on where that organ comes from in the first place.”

    In the United States, nonprofits called organ procurement organizations, or OPOs, are responsible for finding and evaluating potential donors, interacting with grieving families and hospital administrations, and recovering and delivering organs — all while following the federal laws that serve as both their mandate and guardrails. Recent studies estimate that obstacles and inefficiencies lead to thousands of organs going uncollected every year, even as the demand for transplants continues to grow.

    “There’s been little transparent data on organ procurement,” argues Adam. Working with MIT computer science professors Marzyeh Ghassemi and Ashia Wilson, and in collaboration with stakeholders in organ procurement, Adam led a project to create a dataset called ORCHID: Organ Retrieval and Collection of Health Information for Donation. ORCHID contains a decade of clinical, financial, and administrative data from six OPOs.

    “Our goal is for the ORCHID database to have an impact in how organ procurement is understood, internally and externally,” says Ghassemi.

    Efficiency and equity 

    It was looking to make an impact that drew Adam to SES and MIT. With a background in applied math and experience in strategy consulting, solving problems with technical components sits right in his wheelhouse.

    “I really missed challenging technical problems from a statistics and machine learning standpoint,” he says of his time in consulting. “So I went back and got a master’s in data science, and over the course of my master’s got involved in a bunch of academic research projects in a few different fields, including biology, management science, and public policy. What I enjoyed most were some of the more social science-focused projects that had immediate impact.”

    As a grad student in SES, Adam’s research focuses on using statistical tools to uncover health-care inequities, and developing machine learning approaches to address them. “Part of my dissertation research focuses on building tools that can improve equity in clinical trials and other randomized experiments,” he explains.

    One recent example of Adam’s work: developing a novel method to stop clinical trials early if the treatment has an unintended harmful effect for a minority group of participants. “I’ve also been thinking about ways to increase minority representation in clinical trials through improved patient recruitment,” he adds.

    Racial inequities in health care extend into organ transplantation, where a majority of wait-listed patients are not white — far in excess of their demographic groups’ proportion to the overall population. There are fewer organ donations from many of these communities, due to various obstacles in need of better understanding if they are to be overcome. 

    “My work in organ transplantation began on the allocation side,” explains Adam. “In work under review, we examined the role of race in the acceptance of heart, liver, and lung transplant offers by physicians on behalf of their patients. We found that Black race of the patient was associated with significantly lower odds of organ offer acceptance — in other words, transplant doctors seemed more likely to turn down organs offered to Black patients. This trend may have multiple explanations, but it is nevertheless concerning.”

    Adam’s research has also found that donor-candidate race match was associated with significantly higher odds of offer acceptance, an association that Adam says “highlights the importance of organ donation from racial minority communities, and has motivated our work on equitable organ procurement.”

    Working with Ghassemi through the IDSS Initiative on Combatting Systemic Racism, Adam was introduced to OPO stakeholders looking to collaborate. “It’s this opportunity to impact not only health-care efficiency, but also health-care equity, that really got me interested in this research,” says Adam.

    Play video

    MIT Initiative on Combatting Systemic Racism – HealthcareVideo: IDSS

    Making an impact

    Creating a database like ORCHID means solving problems in multiple domains, from the technical to the political. Some efforts never overcome the first step: getting data in the first place. Thankfully, several OPOs were already seeking collaborations and looking to improve their performance.

    “We have been lucky to have a strong partnership with the OPOs, and we hope to work together to find important insights to improve efficiency and equity,” says Ghassemi.

    The value of a database like ORCHID is in its potential for generating new insights, especially through quantitative analysis with statistics and computing tools like machine learning. The potential value in ORCHID was recognized with an MIT Prize for Open Data, an MIT Libraries award highlighting the importance and impact of research data that is openly shared.

    “It’s nice that the work got some recognition,” says Adam of the prize. “And it was cool to see some of the other great open data work that’s happening at MIT. I think there’s real impact in releasing publicly available data in an important and understudied domain.”

    All the same, Adam knows that building the database is only the first step.

    “I’m very interested in understanding the bottlenecks in the organ procurement process,” he explains. “As part of my thesis research, I’m exploring this by modeling OPO decision-making using causal inference and structural econometrics.”

    Using insights from this research, Adam also aims to evaluate policy changes that can improve both equity and efficiency in organ procurement. “And we’re hoping to recruit more OPOs, and increase the amount of data we’re releasing,” he says. “The dream state is every OPO joins our collaboration and provides updated data every year.”

    Adam is excited to see how other researchers might use the data to address inefficiencies in organ procurement. “Every organ donor saves between three and four lives,” he says. “So every research project that comes out of this dataset could make a real impact.” More

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    Improving drug development with a vast map of the immune system

    The human immune system is a network made up of trillions of cells that are constantly circulating throughout the body. The cellular network orchestrates interactions with every organ and tissue to carry out an impossibly long list of functions that scientists are still working to understand. All that complexity limits our ability to predict which patients will respond to treatments and which ones might suffer debilitating side effects.

    The issue often leads pharmaceutical companies to stop developing drugs that could help certain patients, halting clinical trials even when drugs show promising results for some people.

    Now, Immunai is helping to predict how patients will respond to treatments by building a comprehensive map of the immune system. The company has assembled a vast database it calls AMICA, that combines multiple layers of gene and protein expression data in cells with clinical trial data to match the right drugs to the right patients.

    “Our starting point was creating what I call the Google Maps for the immune system,” Immunai co-founder and CEO Noam Solomon says. “We started with single-cell RNA sequencing, and over time we’ve added more and more ‘omics’: genomics, proteomics, epigenomics, all to measure the immune system’s cellular expression and function, to measure the immune environment holistically. Then we started working with pharmaceutical companies and hospitals to profile the immune systems of patients undergoing treatments to really get to the root mechanisms of action and resistance for therapeutics.”

    Immunai’s big data foundation is a result of its founders’ unique background. Solomon and co-founder Luis Voloch ’13, SM ’15 hold degrees in mathematics and computer science. In fact, Solomon was a postdoc in MIT’s Department of Mathematics at the time of Immunai’s founding.

    Solomon frames Immunai’s mission as stopping the decades-long divergence of computer science and the life sciences. He believes the single biggest factor driving the explosion of computing has been Moore’s Law — our ability to exponentially increase the number of transistors on a chip over the past 60 years. In the pharmaceutical industry, the reverse is happening: By one estimate, the cost of developing a new drug roughly doubles every nine years. The phenomenon has been dubbed Eroom’s Law (“Eroom” for “Moore” spelled backward).

    Solomon sees the trend eroding the case for developing new drugs, with huge consequences for patients.

    “Why should pharmaceutical companies invest in discovery if they won’t get a return on investment?” Solomon asks. “Today, there’s only a 5 to 10 percent chance that any given clinical trial will be successful. What we’ve built through a very robust and granular mapping of the immune system is a chance to improve the preclinical and clinical stages of drug development.”

    A change in plans

    Solomon entered Tel Aviv University when he was 14 and earned his bachelor’s degree in computer science by 19. He earned two PhDs in Israel, one in computer science and the other in mathematics, before coming to MIT in 2017 as a postdoc to continue his mathematical research career.

    That year Solomon met Voloch, who had already earned bachelor’s and master’s degrees in math and computer science from MIT. But the researchers were soon exposed to a problem that would take them out of their comfort zones and change the course of their careers.

    Voloch’s grandfather was receiving a cocktail of treatments for cancer at the time. The cancer went into remission, but he suffered terrible side effects that caused him to stop taking his medication.

    Voloch and Solomon began wondering if their expertise could help patients like Voloch’s grandfather.

    “When we realized we could make an impact, we made the difficult decision to stop our academic pursuits and start a new journey,” Solomon recalls. “That was the starting point for Immunai.”

    Voloch and Solomon soon partnered with Immunai scientific co-founders Ansu Satpathy, a researcher at Stanford University at the time, and Danny Wells, a researcher at the Parker Institute for Cancer Immunotherapy. Satpathy and Wells had shown that single-cell RNA sequencing could be used to gain insights into why patients respond differently to a common cancer treatment.

    The team began analyzing single-cell RNA sequencing data published in scientific papers, trying to link common biomarkers with patient outcomes. Then they integrated data from the United Kingdom’s Biobank public health database, finding they were able to improve their models’ predictions. Soon they were incorporating data from hospitals, academic research institutions, and pharmaceutical companies, analyzing information about the structure, function, and environment of cells — multiomics — to get a clearer picture of immune activity.

    “Single cell sequencing gives you metrics you can measure in thousands of cells, where you can look at 20,000 different genes, and those metrics give you an immune profile,” Solomon explains. “When you measure all of that over time, especially before and after getting therapy, and compare patients who do respond with patients who don’t, you can apply machine learning models to understand why.”

    Those data and models make up AMICA, what Immunai calls the world’s largest cell-level immune knowledge base. AMICA stands for Annotated Multiomic Immune Cell Atlas. It analyzes single cell multiomic data from almost 10,000 patients and bulk-RNA data from 100,000 patients across more than 800 cell types and 500 diseases.

    At the core of Immunai’s approach is a focus on the immune system, which other companies shy away from because of its complexity.

    “We don’t want to be like other groups that are studying mainly tumor microenvironments,” Solomon says. “We look at the immune system because the immune system is the common denominator. It’s the one system that is implicated in every disease, in your body’s response to everything that you encounter, whether it’s a viral infection or bacterial infection or a drug that you are receiving — even how you are aging.”

    Turning data into better treatments

    Immunai has already partnered with some of the largest pharmaceutical companies in the world to help them identify promising treatments and set up their clinical trials for success. Immunai’s insights can help partners make critical decisions about treatment schedules, dosing, drug combinations, patient selection, and more.

    “Everyone is talking about AI, but I think the most exciting aspect of the platform we have built is the fact that it’s vertically integrated, from wet lab to computational modeling with multiple iterations,” Solomon says. “For example, we may do single-cell immune profiling of patient samples, then we upload that data to the cloud and our computational models come up with insights, and with those insights we do in vitro or in vivo validation to see if our models are right and iteratively improve them.”

    Ultimately Immunai wants to enable a future where lab experiments can more reliably turn into impactful new recommendations and treatments for patients.

    “Scientists can cure nearly every type of cancer, but only in mice,” Solomon says. “In preclinical models we know how to cure cancer. In human beings, in most cases, we still don’t. To overcome that, most scientists are looking for better ex vivo or in vivo models. Our approach is to be more agnostic as to the model system, but feed the machine with more and more data from multiple model systems. We’re demonstrating that our algorithms can repeatedly beat the top benchmarks in identifying the top preclinical immune features that match to patient outcomes.” More

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    in Data Management & Statistics

    This 3D printer can figure out how to print with an unknown material

    While 3D printing has exploded in popularity, many of the plastic materials these printers use to create objects cannot be easily recycled. While new sustainable materials are emerging for use in 3D printing, they remain difficult to adopt because 3D printer settings need to be adjusted for each material, a process generally done by hand.

    To print a new material from scratch, one must typically set up to 100 parameters in software that controls how the printer will extrude the material as it fabricates an object. Commonly used materials, like mass-manufactured polymers, have established sets of parameters that were perfected through tedious, trial-and-error processes.

    But the properties of renewable and recyclable materials can fluctuate widely based on their composition, so fixed parameter sets are nearly impossible to create. In this case, users must come up with all these parameters by hand.

    Researchers tackled this problem by developing a 3D printer that can automatically identify the parameters of an unknown material on its own.

    A collaborative team from MIT’s Center for Bits and Atoms (CBA), the U.S. National Institute of Standards and Technology (NIST), and the National Center for Scientific Research in Greece (Demokritos) modified the extruder, the “heart” of a 3D printer, so it can measure the forces and flow of a material.

    These data, gathered through a 20-minute test, are fed into a mathematical function that is used to automatically generate printing parameters. These parameters can be entered into off-the-shelf 3D printing software and used to print with a never-before-seen material. 

    The automatically generated parameters can replace about half of the parameters that typically must be tuned by hand. In a series of test prints with unique materials, including several renewable materials, the researchers showed that their method can consistently produce viable parameters.

    This research could help to reduce the environmental impact of additive manufacturing, which typically relies on nonrecyclable polymers and resins derived from fossil fuels.

    “In this paper, we demonstrate a method that can take all these interesting materials that are bio-based and made from various sustainable sources and show that the printer can figure out by itself how to print those materials. The goal is to make 3D printing more sustainable,” says senior author Neil Gershenfeld, who leads CBA.

    His co-authors include first author Jake Read a graduate student in the CBA who led the printer development; Jonathan Seppala, a chemical engineer in the Materials Science and Engineering Division of NIST; Filippos Tourlomousis, a former CBA postdoc who now heads the Autonomous Science Lab at Demokritos; James Warren, who leads the Materials Genome Program at NIST; and Nicole Bakker, a research assistant at CBA. The research is published in the journal Integrating Materials and Manufacturing Innovation.

    Shifting material properties

    In fused filament fabrication (FFF), which is often used in rapid prototyping, molten polymers are extruded through a heated nozzle layer-by-layer to build a part. Software, called a slicer, provides instructions to the machine, but the slicer must be configured to work with a particular material.

    Using renewable or recycled materials in an FFF 3D printer is especially challenging because there are so many variables that affect the material properties.

    For instance, a bio-based polymer or resin might be composed of different mixes of plants based on the season. The properties of recycled materials also vary widely based on what is available to recycle.

    “In ‘Back to the Future,’ there is a ‘Mr. Fusion’ blender where Doc just throws whatever he has into the blender and it works [as a power source for the DeLorean time machine]. That is the same idea here. Ideally, with plastics recycling, you could just shred what you have and print with it. But, with current feed-forward systems, that won’t work because if your filament changes significantly during the print, everything would break,” Read says.

    To overcome these challenges, the researchers developed a 3D printer and workflow to automatically identify viable process parameters for any unknown material.

    They started with a 3D printer their lab had previously developed that can capture data and provide feedback as it operates. The researchers added three instruments to the machine’s extruder that take measurements which are used to calculate parameters.

    A load cell measures the pressure being exerted on the printing filament, while a feed rate sensor measures the thickness of the filament and the actual rate at which it is being fed through the printer.

    “This fusion of measurement, modeling, and manufacturing is at the heart of the collaboration between NIST and CBA, as we work develop what we’ve termed ‘computational metrology,’” says Warren.

    These measurements can be used to calculate the two most important, yet difficult to determine, printing parameters: flow rate and temperature. Nearly half of all print settings in standard software are related to these two parameters. 

    Deriving a dataset

    Once they had the new instruments in place, the researchers developed a 20-minute test that generates a series of temperature and pressure readings at different flow rates. Essentially, the test involves setting the print nozzle at its hottest temperature, flowing the material through at a fixed rate, and then turning the heater off.

    “It was really difficult to figure out how to make that test work. Trying to find the limits of the extruder means that you are going to break the extruder pretty often while you are testing it. The notion of turning the heater off and just passively taking measurements was the ‘aha’ moment,” says Read.

    These data are entered into a function that automatically generates real parameters for the material and machine configuration, based on relative temperature and pressure inputs. The user can then enter those parameters into 3D printing software and generate instructions for the printer.

    In experiments with six different materials, several of which were bio-based, the method automatically generated viable parameters that consistently led to successful prints of a complex object.

    Moving forward, the researchers plan to integrate this process with 3D printing software so parameters don’t need to be entered manually. In addition, they want to enhance their workflow by incorporating a thermodynamic model of the hot end, which is the part of the printer that melts the filament.

    This collaboration is now more broadly developing computational metrology, in which the output of a measurement is a predictive model rather than just a parameter. The researchers will be applying this in other areas of advanced manufacturing, as well as in expanding access to metrology.

    “By developing a new method for the automatic generation of process parameters for fused filament fabrication, this study opens the door to the use of recycled and bio-based filaments that have variable and unknown behaviors. Importantly, this enhances the potential for digital manufacturing technology to utilize locally sourced sustainable materials,” says Alysia Garmulewicz, an associate professor in the Faculty of Administration and Economics at the University of Santiago in Chile who was not involved with this work.

    This research is supported, in part, by the National Institute of Standards and Technology and the Center for Bits and Atoms Consortia. More

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    in Data Management & Statistics

    Characterizing social networks

    People tend to connect with others who are like them. Alumni from the same alma mater are more likely to collaborate over a research project together, or individuals with the same political beliefs are more likely to join the same political parties, attend rallies, and engage in online discussions. This sociology concept, called homophily, has been observed in many network science studies. But if like-minded individuals cluster in online and offline spaces to reinforce each other’s ideas and form synergies, what does that mean for society?

    Researchers at MIT wanted to investigate homophily further to understand how groups of three or more interact in complex societal settings. Prior research on understanding homophily has studied relationships between pairs of people. For example, when two members of Congress co-sponsor a bill, they are likely to be from the same political party.

    However, less is known about whether group interactions between three or more people are likely to occur between similar individuals. If three members of Congress co-sponsor a bill together, are all three likely to be members of the same party, or would we expect more bipartisanship? When the researchers tried to extend traditional methods to measure homophily in these larger group interactions, they found the results can be misleading.

    “We found that homophily observed in pairs, or one-to-one interactions, can make it seem like there’s more homophily in larger groups than there really is,” says Arnab Sarker, graduate student in the Institute for Data, Systems and Society (IDSS) and lead author of the study published in Proceedings of the National Academy of Sciences. “The previous measure didn’t account for the way in which two people already know each other in friendship settings,” he adds.

    To address this issue, Sarker, along with co-authors Natalie Northrup ’22 and Ali Jadbabaie, the JR East Professor of Engineering, head of the Department of Civil and Environmental Engineering, and core faculty member of IDSS, developed a new way of measuring homophily. Borrowing tools from algebraic topology, a subfield in mathematics typically applied in physics, they developed a new measure to understand whether homophily occurred in group interactions.

    The new measure, called simplicial homophily, separates the homophily seen in one-on-one interactions from those in larger group interactions and is based on the mathematical concept of a simplicial complex. The researchers tested this new measure with real-world data from 16 different datasets and found that simplicial homophily provides more accurate insights into how similar things interact in larger groups. Interestingly, the new measure can better identify instances where there is a lack of similarity in larger group interactions, thus rectifying a weakness observed in the previous measure.

    One such example of this instance was demonstrated in the dataset from the global hotel booking website, Trivago. They found that when travelers are looking at two hotels in one session, they often pick hotels that are close to one another geographically. But when they look at more than two hotels in one session, they are more likely to be searching for hotels that are farther apart from one another (for example, if they are taking a vacation with multiple stops). The new method showed “anti-homophily” — instead of similar hotels being chosen together, different hotels were chosen together.

    “Our measure controls for pairwise connections and is suggesting that there’s more diversity in the hotels that people are looking for as group size increases, which is an interesting economic result,” says Sarker.

    Additionally, they discovered that simplicial homophily can help identify when certain characteristics are important for predicting if groups will interact in the future. They found that when there’s a lot of similarity or a lot of difference between individuals who already interact in groups, then knowing individual characteristics can help predict their connection to each other in the future.

    Northrup was an undergraduate researcher on the project and worked with Sarker and Jadbabaie over three semesters before she graduated. The project gave her an opportunity to take some of the concepts she learned in the classroom and apply them.

    “Working on this project, I really dove into building out the higher-order network model, and understanding the network, the math, and being able to implement it at a large scale,” says Northrup, who was in the civil and environmental engineering systems track with a double major in economics.

    The new measure opens up opportunities to study complex group interactions in a broad range of network applications, from ecology to traffic and socioeconomics. One of the areas Sarker has interest in exploring is the group dynamics of people finding jobs through social networks. “Does higher-order homophily affect how people get information about jobs?” he asks.    

    Northrup adds that it could also be used to evaluate interventions or specific policies to connect people with job opportunities outside of their network. “You can even use it as a measurement to evaluate how effective that might be.”

    The research was supported through funding from a Vannevar Bush Fellowship from the Office of the U.S. Secretary of Defense and from the U.S. Army Research Office Multidisciplinary University Research Initiative. More

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    in Data Management & Statistics

    New software enables blind and low-vision users to create interactive, accessible charts

    A growing number of tools enable users to make online data representations, like charts, that are accessible for people who are blind or have low vision. However, most tools require an existing visual chart that can then be converted into an accessible format.

    This creates barriers that prevent blind and low-vision users from building their own custom data representations, and it can limit their ability to explore and analyze important information.

    A team of researchers from MIT and University College London (UCL) wants to change the way people think about accessible data representations.

    They created a software system called Umwelt (which means “environment” in German) that can enable blind and low-vision users to build customized, multimodal data representations without needing an initial visual chart.

    Umwelt, an authoring environment designed for screen-reader users, incorporates an editor that allows someone to upload a dataset and create a customized representation, such as a scatterplot, that can include three modalities: visualization, textual description, and sonification. Sonification involves converting data into nonspeech audio.

    The system, which can represent a variety of data types, includes a viewer that enables a blind or low-vision user to interactively explore a data representation, seamlessly switching between each modality to interact with data in a different way.

    The researchers conducted a study with five expert screen-reader users who found Umwelt to be useful and easy to learn. In addition to offering an interface that empowered them to create data representations — something they said was sorely lacking — the users said Umwelt could facilitate communication between people who rely on different senses.

    “We have to remember that blind and low-vision people aren’t isolated. They exist in these contexts where they want to talk to other people about data,” says Jonathan Zong, an electrical engineering and computer science (EECS) graduate student and lead author of a paper introducing Umwelt. “I am hopeful that Umwelt helps shift the way that researchers think about accessible data analysis. Enabling the full participation of blind and low-vision people in data analysis involves seeing visualization as just one piece of this bigger, multisensory puzzle.”

    Joining Zong on the paper are fellow EECS graduate students Isabella Pedraza Pineros and Mengzhu “Katie” Chen; Daniel Hajas, a UCL researcher who works with the Global Disability Innovation Hub; and senior author Arvind Satyanarayan, associate professor of computer science at MIT who leads the Visualization Group in the Computer Science and Artificial Intelligence Laboratory. The paper will be presented at the ACM Conference on Human Factors in Computing.

    De-centering visualization

    The researchers previously developed interactive interfaces that provide a richer experience for screen reader users as they explore accessible data representations. Through that work, they realized most tools for creating such representations involve converting existing visual charts.

    Aiming to decenter visual representations in data analysis, Zong and Hajas, who lost his sight at age 16, began co-designing Umwelt more than a year ago.

    At the outset, they realized they would need to rethink how to represent the same data using visual, auditory, and textual forms.

    “We had to put a common denominator behind the three modalities. By creating this new language for representations, and making the output and input accessible, the whole is greater than the sum of its parts,” says Hajas.

    To build Umwelt, they first considered what is unique about the way people use each sense.

    For instance, a sighted user can see the overall pattern of a scatterplot and, at the same time, move their eyes to focus on different data points. But for someone listening to a sonification, the experience is linear since data are converted into tones that must be played back one at a time.

    “If you are only thinking about directly translating visual features into nonvisual features, then you miss out on the unique strengths and weaknesses of each modality,” Zong adds.

    They designed Umwelt to offer flexibility, enabling a user to switch between modalities easily when one would better suit their task at a given time.

    To use the editor, one uploads a dataset to Umwelt, which employs heuristics to automatically creates default representations in each modality.

    If the dataset contains stock prices for companies, Umwelt might generate a multiseries line chart, a textual structure that groups data by ticker symbol and date, and a sonification that uses tone length to represent the price for each date, arranged by ticker symbol.

    The default heuristics are intended to help the user get started.

    “In any kind of creative tool, you have a blank-slate effect where it is hard to know how to begin. That is compounded in a multimodal tool because you have to specify things in three different representations,” Zong says.

    The editor links interactions across modalities, so if a user changes the textual description, that information is adjusted in the corresponding sonification. Someone could utilize the editor to build a multimodal representation, switch to the viewer for an initial exploration, then return to the editor to make adjustments.

    Helping users communicate about data

    To test Umwelt, they created a diverse set of multimodal representations, from scatterplots to multiview charts, to ensure the system could effectively represent different data types. Then they put the tool in the hands of five expert screen reader users.

    Study participants mostly found Umwelt to be useful for creating, exploring, and discussing data representations. One user said Umwelt was like an “enabler” that decreased the time it took them to analyze data. The users agreed that Umwelt could help them communicate about data more easily with sighted colleagues.

    “What stands out about Umwelt is its core philosophy of de-emphasizing the visual in favor of a balanced, multisensory data experience. Often, nonvisual data representations are relegated to the status of secondary considerations, mere add-ons to their visual counterparts. However, visualization is merely one aspect of data representation. I appreciate their efforts in shifting this perception and embracing a more inclusive approach to data science,” says JooYoung Seo, an assistant professor in the School of Information Sciences at the University of Illinois at Urbana-Champagne, who was not involved with this work.

    Moving forward, the researchers plan to create an open-source version of Umwelt that others can build upon. They also want to integrate tactile sensing into the software system as an additional modality, enabling the use of tools like refreshable tactile graphics displays.

    “In addition to its impact on end users, I am hoping that Umwelt can be a platform for asking scientific questions around how people use and perceive multimodal representations, and how we can improve the design beyond this initial step,” says Zong.

    This work was supported, in part, by the National Science Foundation and the MIT Morningside Academy for Design Fellowship. More