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BUSM Research
Data Science Core Opens for Business
BUSM faculty, particularly the genomics research community, asked for help with data analysis in 2020. BUMC Provost and BUSM Dean Karen Antman, MD, held a data science workshop in February of that year, the result of which was a decision to create a service core staffed by faculty scientists to provide the level of analysis and bioinformatics—big data analysis of large data sets using computer and statistical analyses on biological data— necessary for researchers to further their work.
The COVID-19 pandemic put that effort on hold until September 2021, when the search for data science faculty resumed.
The Applied Data Science Core (ADSC) is now open for business with Assistant Professor of Computational Biomedicine Chao Zhang, PhD, and Associate Professor of Computational Biomedicine Ignaty Leshchiner, PhD, who joined Zhang in May 2022.
“The goal is to have the analytical capabilities on campus needed to support and advance the biomedical research of the BUSM faculty,” says Andrew W. Taylor, PhD, associate dean for research. “Bioinformatics and biostatistical programmers know how to handle large data sets.”
Taylor adds that ADSC faculty will also conduct research in their specialty areas.
“Applying data sciences is foundational for advancing our field, and we can’t wait to collaborate with the new core,” says Darrell Kotton, MD, the David C. Seldin Professor of Medicine and director of the BU/BMC Center for Regenerative Medicine (CReM).
The new service complements BU President Robert Brown’s vision for the University to become a leader in the data science field, realized in the ongoing construction of a new Center for Computing & Data Sciences on Commonwealth Avenue.
“There’s a lot of excitement at BU for data science,” says Nelson Lau, PhD, associate professor of biochemistry and director of BU’s Genome Sciences Institute (GSI). “In the biomedicine field we are awash in genomic and sequencing data; even labs that never managed data before find they need to in order to stay current and competitive. Anyone doing animal or disease research requires genetic sequencing that can involve gigabytes, even terabytes, of data to map diseases back to the genomes
and compare healthy to diseased to get to even a fundamental understanding of what you are working with.”
Lau is already working with Zhang on a project, analyzing RNA data sequenced from mosquitos collected at field stations in Connecticut to see what viruses might be present apart from commonly known ones, like West Nile and Eastern Equine Encephalitis.
While Lau is trained in bioinformatics and his lab has two bioinformatics specialists, he says that it’s impossible to help everyone who needs specialized data analysis: “Many PIs [principal investigators] like myself have to take care of our own research first.” Lau worked with Taylor and Dean Antman to democratize access.
“Even with centers as successful as the CReM and GSI, where we have our own bioinformatics groups, it would be great to see more labs at BUSM have access to this type of analysis, too,” he adds.
Before this new service was available, BUSM researchers without direct access to data analysis specialists either found another researcher to help them or contracted with an outside company.
“Instead of sending [their data] to an outside company, we have the opportunity to interact with them to get a better result,” says Zhang, who has a doctorate in computer science and a master’s degree in statistics.
“Typically, for-profit companies do basic analysis for everyone. We are researchers, and we will try to help them interpret and understand the data; the deeper background of the whole story,” explains Zhang. “The ultimate goal is to use technology on large-scale data to solve those complicated questions.”
His specialty is computational biomedicine, the application of computer methodology to help in the diagnosis and treatment of disease. Zhang says one of the applications could be genomics analysis of a tumor sample to find a better treatment specific to that patient.
“A lot of people do data science projects that are data-heavy,” said Vasan Ramachandran, MD, professor of medicine and epidemiology at BUSM and SPH, and principal investigator and director of the Framingham Heart Study (FHS). He compares the new data center to a community pool where a lot of people can swim without the expense of building individual pools.
“Having a centralized data core would cater to a larger group of researchers where they could find one-stop expertise. The ADSC would be able to work together with researchers to really meet what has heretofore been an unmet need,” he says.
Ramachandran, who believes there may be as many unfunded as there are funded research projects underway at BUSM, says that the ability to do data analysis inhouse may also help in getting grants: “They assume you have the infrastructure.” “I think it will be helpful in applying for grants,” agrees Lau. “There’s just a higher chance of [the project] succeeding. Instead of begging for help from another institution, you can just go down the hall and talk to someone on the same team. It’s a more personalized experience.”
Ramachandran looks forward to future computerized data analysis that can combine data from heterogenous sources. For example, Ramachandran’s RURAL Cohort Study is evaluating the underlying health risks in rural areas.
“Why are people in rural areas challenged in terms of their health?” he asks. The answer may lie in a combination of reasons that involve varied data sources like medical and health records, genetics, and diet that can be stored in entirely different formats.
“The underlying architecture of the data is different befitting the multidimensional nature of the disease,” Ramachandran says. “The information is siloed but understanding risk and building health takes a multifaceted approach and there isn’t one expert who can coordinate the data. The ADSC core hopes to provide a resource with complementary expertise in different domains.”
According to Taylor, who oversees the running of BUSM cores, the ADSC will be initially funded by the dean’s office, with the possibility of additional funding coming through data science instruction and student training. “As time goes by, it should be supported by subcontracts and multiple principal investigator grants,” he says. n
CTE Center Study of Former Notre Dame Football Players Finds College Players More Likely to Have Brain Disorders
The link between playing football and a heightened risk of developing later-life brain disorders like chronic traumatic encephalopathy (CTE) and amyotrophic lateral sclerosis (ALS) has received increasing attention over the past 15 years. While National Football League (NFL) players are more likely to die from CTE and ALS and more likely to report cognitive impairment, behavioral changes, and dementia, similar studies of former college football players have not been reported.
In a study published in JAMA Network Open, BU CTE Center researchers report on the long-term health outcomes and mortality rates of former University of Notre Dame football players who were seniors on the 1964–1980 rosters. Compared to a representative sample of same-age men in the general population, former Notre Dame players were five times more likely to report cognitive impairment diagnoses, two-anda-half times more likely to report recurrent headaches, and 65 percent more likely to have cardiovascular disorders during life, based on health surveys completed by 216 of the 375 (58 percent) former players still living.
Consistent with reports of former NFL players, mortality due to degenerative brain disease, specifically Parkinson’s disease and ALS, was higher in the former college players compared to the general population, but the researchers caution that the difference did not reach statistical significance. Unexpectedly, mortality from brain and other nervous system cancers was almost four times higher in the former college players compared to the general population.
The study also found positive long-term health outcomes in the former college football players who had a lower prevalence of diabetes during life and an overall lower mortality rate compared to the general population. Specifically, their death rates from heart, circulatory, respiratory and digestive system disorders, and from lung cancer and violence, were significantly lower.
According to the researchers, results of the new study of former college players are overall quite similar to study results of the former professional players. “Similar to studies of other former high-level athletes, we found that former college football players have lower overall mortality and lower risk of death from lung cancer and heart disease,” says corresponding author Robert Stern, PhD, director of clinical research for the BU CTE Center and professor of neurology, neurosurgery, and anatomy & neurobiology at BU School of Medicine. “However, the negative health consequences, especially the brain-related disorders we found in this group of former Notre Dame players, are concerning,” Stern adds. n
Researchers Discover How the Placenta May Be Blocking SARSCoV-2 Transmission to Babies during Pregnancy
While COVID-19 significantly impacts many pregnant women, the rates of transmission from mother to baby in pregnancy are very low. A BUSM study published online in the American Journal of Pathology has demonstrated that ACE-2, the receptor that allows SARS-CoV-2 to enter cells, is found in lower levels in the placentas of women with COVID-19 in pregnancy compared to women with normal (COVID-negative) pregnancies.
“We think that when a woman has COVID-19 in pregnancy, the placenta is shedding ACE-2 as a way to block SARS-CoV-2 from being passed to the fetus,” explains co-corresponding author Elizabeth S. Taglauer, MD, PhD, assistant professor of pediatrics at BUSM.
The study is a collaborative effort between placental/ perinatal researchers at BUSM, Boston Medical Center (BMC), Ke Yuan, PhD, a lung vascular biologist at Boston Children’s Hospital, and Hongpeng Jia, PhD, an ACE-2 expert at Johns Hopkins University. It involved collecting placentas from two groups of women who delivered at BMC from July 2020 to April 2021, an effort led by study coauthor Elisha Wachman, MD, an associate professor of pediatrics at BUSM and a neonatologist at BMC. The first group of women had normal pregnancies and no report of SARS-CoV-2 infection; the second were SARSCoV-2 positive and had active COVID-19 disease during pregnancy. They then observed the ACE-2 expression in their placentas under the microscope and compared placental ACE-2 expression using genetic and protein analysis techniques. n
Lipid and Glucose Levels at Age 35 Associated with Alzheimer’s Disease
Ignoring cholesterol and glucose levels as early as age 35 may impact your chances of getting Alzheimer’s disease (AD) later in life. According to BUSM researchers, lower levels of high-density cholesterol (HDL) and high triglyceride levels measured in blood as early as age 35 are associated with a higher incidence of AD several decades later in life. They also found that high blood glucose measured between the ages of 51–60 is associated with risk of AD in the future.
“While our findings confirm other studies that linked cholesterol and glucose levels measured in blood with future risk of Alzheimer’s disease, we have shown for the first time that these associations extend much earlier in life than previously thought,” explains senior author Lindsay A. Farrer, PhD, chief of biomedical genetics at BUSM.
Published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study was conducted using data obtained from Framingham Heart Study participants who were examined at approximately four-year intervals throughout most of their adult lives. Correlations of AD with multiple known risk factors for cardiovascular disease and diabetes (including HDL, LDL, triglycerides, glucose, blood pressure, smoking, and body mass index) were measured at each exam and during three age periods during adulthood: 35–50, 51–60, and 61–70.
According to the researchers, careful management of these factors starting in early adulthood can lower one’s risk of cardiovascular disease and diabetes, as well as Alzheimer’s. “Intervention targeting cholesterol and glucose management starting in early adulthood can help maximize cognitive health in later life,” says Farrer. “The unique design and mission of the Framingham Heart Study, which is a multigeneration, communitybased, prospective study of health that began in 1948, allowed us to link Alzheimer’s to risk factors for heart disease and diabetes measured much earlier in life than possible in most other studies of cognitive decline and dementia.” n
Optimism May Promote Emotional Well-Being by Limiting How Often One Experiences Stressful Situations
The song lyrics “Don’t worry, be happy” may be more accurate than we thought. A growing body of evidence supports an association between optimism and healthy aging, but it is unclear how optimism impacts health.
“When it comes to dealing with dayto-day stressors, such as household chores or arguments, a study published in the Journals of Gerontology, Series B: Psychological Sciences and Social Sciences has found that being more or less optimistic did not make a difference in how older men emotionally reacted to, or recovered from, these stressors. However, optimism appeared to promote emotional well-being by limiting how often older men experience stressful situations or changing the way they interpret situations as stressful.
“This study tests one possible explanation, assessing if more optimistic people handle daily stress more constructively and therefore, enjoy better emotional well-being,” says corresponding author Lewina Lee, PhD, clinical psychologist at the National Center for Posttraumatic Stress Disorder at the VA Boston Healthcare System and assistant professor of psychiatry at BUSM.
The researchers followed 233 older men who first completed an optimism questionnaire; 14 years later, they reported daily stressors along with positive and negative moods on eight consecutive evenings up to three times over an eight-year span. The researchers found more optimistic men reported not only lower negative mood but also more positive mood beyond simply not feeling negative. They also reported having fewer stressors, which was unrelated to their higher positive mood but explained their lower levels of negative mood.
While studies have increasingly supported the idea of optimism as a resource that may promote good health and longevity, we know very little about the underlying mechanisms. “Stress, on the other hand, is known to have a negative impact on our health. By looking at whether optimistic people handle dayto-day stressors differently, our findings add to knowledge about how optimism may promote good health as people age,” says Lee. n
Researchers Race to Understand Long COVID in National Study
For medical providers working with COVID long-haulers, “no two patients are the same,” pointing to the urgency of unraveling the mysteries of post-coronavirus conditions and potential treatments.
Among the uncertainties and worries that living with COVID19 presents, long COVID— lingering effects of the disease that persist longer than four weeks after an initial infection clears—is a big one. Patients with long COVID, sometimes dubbed “COVID long-haulers,” report symptoms ranging from headaches to chronic fatigue to shortness of breath; the long-term impacts of the condition are largely unknown.
To answer the many puzzling questions about long COVID, researchers at BUSM and Boston Medical Center (BMC) are beginning to investigate “post-acute sequelae of SARS-CoV-2 (PASC),” the medical term used for the array of long COVID symptoms. The newly launched project, called the RECOVER (Research COVID to Enhance Recovery) study, is part of a national effort—funded by the National Institutes of Health—that aims to better understand who is at risk, how recovery varies in different people, and what can be done to prevent the condition and treat patients.
Being able to fully understand long COVID starts with being able to properly define it, says Jai Marathe, MBBS, a coprincipal investigator on the RECOVER study. She says that’s been difficult since symptoms are so varied.
“Patients with long COVID may present with a variety of different symptoms, and no two patients are the same,” says Marathe, assistant professor of medicine/ infectious diseases. “The important thing to note is that we are learning about long COVID along with our patients—and we are constantly evaluating our treatment recommendations to address the patients’ needs.
For some, [symptoms] are mild, but can be debilitating for others.”
Marathe is also the founding director of the ReCOVer Long COVID Clinic at BMC, a multidisciplinary clinic with specialties that include neurology and behavioral health and currently has about 85 patients under its care. The RECOVER study will recruit from the clinic and also have a control group of people who are not displaying signs of long COVID.
“The tough part to date has been that studies have used different definitions of long COVID. A well-controlled cohort like this one, with a large number of patients, can help clarify the biological and clinical features that are hallmarks of PASC,” says Nahid Bhadelia, MD, associate professor of medicine/infectious diseases and founding director of BU’s Center for Emerging Infectious Diseases. Bhadelia is a coprincipal investigator on the RECOVER study—which will take place over the next three years— and is helping BMC collaborate with five other Boston–area hospitals that are also a part of the national project.
To learn more about the study and the effects of long COVID, we spoke with Anna Cervantes-Arslanian, a coinvestigator on the project and a neurologist at BMC who works with patients in the long COVID clinic.
What has your experience been like caring for patients with long COVID? Cervantes-Arslanian: In my experience, long COVID symptoms are highly varied. Because of my day-to-day practice in the ICU, most of the patients referred to me are following up after they have been hospitalized with severe illness from COVID-19. Many of these patients had symptoms that could be related to being hospitalized or related to SARS-CoV-2. Now, we’re seeing more people coming to the [long COVID] clinic who were not hospitalized to begin with, some who didn’t even have a respiratory infection.
I am often consulted for severe changes in mental status; sometimes strokes, seizures, and very rarely, other obscure problems after a COVID-19 infection. Now, the number one symptom I’m hearing about is fatigue. People talk about persistent fatigue that is totally different from what their baselines were [before they were infected with COVID-19]. People also talk a lot about brain fog, which is experienced differently for many people, but often described as feeling scatterbrained, or at a loss for words. There are also a lot of patients who have headaches, either a new onset or worsening headaches, or headaches that started with a COVID infection. There are also a lot of symptoms that dovetail into cardiology, such as where people have abnormal and rapid heartbeats depending on if they are laying down or standing up. All of these neurologic symptoms can be debilitating for some people.
What are you and the research team hoping to accomplish by the end of this study? There is a loose definition of post-acute sequelae of SARS-CoV-2, or PASC, so I think clearly defining this syndrome is very important—future research will depend on us being able to communicate what PASC is. Another key question I’d like to answer is, are these symptoms more common in people with SARS-CoV-2 or not? That sounds like a strange question, but we need to have an answer for this. We need a control group, which the RECOVER study will have.
Having the long COVID clinic is also important for specialists to evaluate whether concerns a patient attributes to long COVID are indeed related to the infection reaction or potentially signs of another illness that needs attention. As an example, I had a patient who went to her primary care doctor with a headache after getting COVID-19, and then her doctor referred her to me. Once I saw her, I immediately saw she had a serious problem, possibly a brain tumor, that likely by coincidence appeared after getting COVID.
In your opinion, why is studying long COVID urgently needed right now? This is a brand-new, novel virus that has impacted the whole world. It’s important for us to understand the acute complications— how the virus impacts the body during an infection—and what the long-term effects are going to be. We know that after the flu pandemic in 1918, there was an increased risk for a type of post-viral Parkinson’s disease, so [the long-term effects] are something the medical community is thinking about. What we really don’t know is: Will infected kids have long-term medical problems? Will this impact middleaged adults when they get older? We just don’t know. I’m very interested from a place of curiosity, as well as getting the information as the starting point.
What is most important right now is that we are really paying attention to these patients, because people feel dismissed. Women are more likely to have these symptoms than men, and women are more often dismissed [in medical settings] for vague symptoms.
What do we know about whether the vaccine has any impact on the likelihood of developing long COVID? So far, it seems that being vaccinated makes you less likely to develop long COVID symptoms, but we don’t know for sure. There are a lot of reasons to get vaccinated, so possibly being less likely to develop long COVID is another reason. Long COVID could also be more associated with particular virus variants, but again, we don’t know. There were also stories of some people experiencing improvements in long COVID symptoms after getting the vaccine, which some people point out could be a placebo effect. But there are reasons to think that the immune system is involved with long COVID, so it’s logical to think that providing the spike protein for the boosted immunity can help in the other processes involved. n
