Center for Biomedical Informatics

Boston, MA, United States

Center for Biomedical Informatics

Boston, MA, United States
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Ogunyemi O.,Center for Biomedical Informatics | George S.,Center for Biomedical Informatics | Teklehaimanot S.,Drew University | Baker R.,Center for Biomedical Informatics
AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium | Year: 2013

In a previous paper, we presented initial findings from a study on the feasibility and challenges of implementing teleretinal screening for diabetic retinopathy in an urban safety net setting facing eyecare specialist shortages. This paper presents some final results from that study, which involved six South Los Angeles safety net clinics. A total of 2,732 unique patients were screened for diabetic retinopathy by three ophthalmologist readers, with 1035 receiving a recommendation for referral to specialty care. Referrals included 48 for proliferative diabetic retinopathy, 115 for severe non-proliferative diabetic retinopathy (NPDR), 247 for moderate NPDR, 246 for mild NPDR, 97 for clinically significant macular edema, and 282 for a non-diabetic condition, such as glaucoma. Image quality was also assessed, with ophthalmologist readers grading 4% to 13% of retinal images taken at the different clinics as being inadequate for any diagnostic interpretation.

Fiks A.G.,Pediatric Research Consortium | Fiks A.G.,Center for Biomedical Informatics | Fiks A.G.,Center for Pediatric Clinical Effectiveness | Fiks A.G.,Children's Hospital of Philadelphia | And 7 more authors.
Pediatrics | Year: 2013

Objectives: To describe the association between parents' attentiondeficit/hyperactivity disorder (ADHD) treatment preferences and goals and treatment initiation. Methods: Parents/guardians of children aged 6 to 12 years diagnosed with ADHD in the past 18 months and not currently receiving combined treatment (both medication and behaviortherapy [BT]) were recruited from 8 primary care sites and an ADHD treatment center. Parents completed the ADHD Preference and Goal Instrument, a validated measure, and reported treatment receipt at 6 months. Logistic regression was used to analyze the association of baseline preferences and goals with treatment initiation. Using linear regression, we compared the change in preferences and goals over 6 months for children who initiated treatment versus others. Results: The study included 148 parents/guardians. Baseline medication and BT preference were associated with treatment initiation (odds ratio [OR]: 2.6 [95% confidence interval (CI):1.2-5.5] and 2.2 [95% CI: 1.0-5.1], respectively). The goal of academic achievement was associated with medication initiation (OR: 2.1 [95% CI: 1.3-3.4]) and the goal of behavioral compliance with initiation of BT (OR: 1.6 [95% CI: 1.1-2.4]). At 6 months, parents whose children initiated medication or BT compared with others had decreased academic and behavioral goals, suggesting their goals were attained. However, only those initiating BT had diminished interpersonal relationship goals. Conclusions: Parental treatment preferences were associated with treatment initiation, and those with distinct goals selected different treatments. Results support the formal measurement of preferences and goals in practice as prioritized in recent national guidelines for ADHD management. © 2013 by the American Academy of Pediatrics.

INDIANAPOLIS -- Burke Mamlin, MD, and Paul Biondich, MD, of the Regenstrief Institute and Indiana University School of Medicine will be honored on November 12 with the 2016 Donald A.B. Lindberg Award for Innovation in Informatics. The award will be presented by the American Medical Informatics Association (AMIA), the largest international professional biomedical informatics association, at its annual symposium. Dr. Mamlin, an internist, and Dr. Biondich, a pediatrician, are pioneers in the development, testing, and use of open source software to support the delivery of health care in developing countries. AMIA's prestigious Lindberg award recognizes individuals for a technological, research, or educational contribution that advances biomedical informatics. The work leading to the award must be conducted in a not-for-profit setting, and the adoption of the particular advance by the informatics community must be on a national or international level. The honoring of Dr. Mamlin and Dr. Biondich is the first time that the Lindberg award has been presented to more than one person. OpenMRS, the system that grew from their initial concept, is designed to be usable in resource poor environments and can be customized with modules -- laboratory test ordering and reporting, for example, or public health reporting -- without programming. It is intended as a medical record system platform that can be adopted and modified wherever required, eliminating the need to develop a system from scratch. In 2015 when commercial electronic medical record systems weren't equipped to handle the problems encountered in the Ebola outbreak in West Africa, OpenMRS, supported by the worldwide OpenMRS community, was adapted to help with the management of the large number of patients in extreme conditions. Today, the OpenMRS community forms the world's largest open source project to develop health information technology for resource-constrained environments. The OpenMRS platform is deployed in more than 80 countries throughout the world. Dr. Mamlin is a graduate of Wesleyan University and earned a medical degree from Indiana University. Dr. Biondich is a graduate of Emory University and earned a medical degree from the University of Florida. Both completed National Library of Medicine-supported medical informatics fellowships at the Regenstrief Institute and joined the institute's Center for Biomedical Informatics in 2001. Dr. Mamlin is an associate professor of clinical medicine and Dr. Biondich is an associate professor of pediatrics at IU School of Medicine. In addition to OpenMRS, of which he is the development lead, Dr. Mamlin's work has focused on computerized physician order-entry and provider interfaces with medical record systems. Dr. Biondich, who leads the Global Health Informatics program at the Regenstrief Institute, also developed a decision support system, Child Health Improvement through Computer Automation (CHICA), and leads global efforts on health information exchanges within resource emerging environments. "With amazing technical, organizational, and leadership skills necessary to make their dreams a reality, Drs. Biondich and Mamlin have helped create a movement that is supporting the care for the most vulnerable among us," said Shaun Grannis, MD, interim director of the Regenstrief Institute's CBMI, associate professor of family medicine at IU School of Medicine and a fellow of the American College of Medical Informatics. "This recognition is well deserved." The Regenstrief Institute's CBMI is an internationally recognized leader in biomedical informatics focused on improving health care through informatics. The center develops and applies health information technology solutions to generate knowledge about health, disease and treatment, help clinicians make optimal decisions, empower patients, and inform healthcare policy. The center focuses on clinical applications, computer-based decision support, data mining, advanced analytics, healthcare information standards, and global health. These applications and tools are widely recognized for their roles in improving quality of care, efficiency of healthcare delivery, reducing medical errors, and enhancing patient safety. Approximately 2500 informatics professionals are expected to attended AMIA's 2016 symposium in Chicago where Dr. Mamlin and Dr. Biondich will be honored.

INDIANAPOLIS -- Have a dental emergency? Your smartphone may be able to help you avoid an unnecessary trip to the hospital. A team mentored by Thankam Thyvalikakath, DMD, PhD, now of the Indiana University School of Dentistry and of the Regenstrief Institute, has developed and tested a novel mobile application enabling smartphones to capture and transmit images from inside the mouth, along with details on the dental emergency, to provide the information dentists need to make a decision on what -- and how urgently -- care is needed. Seeking to improve emergency dental care, the researchers developed DentaCom, a cell phone application that enables dentists to make decisions when they cannot see the patient. "A Prototype Mobile Application for Triaging Dental Emergencies" is published in the October 2016 issue of The Journal of the American Dental Association and is featured on the issue's cover. The authors were at the University of Pittsburgh at the time of the study. The new app guides individuals with real or suspected dental emergencies through a series of questions designed to capture clinically meaningful data via familiar smartphone functions. In the study, all participants were able to complete a guided report on their dental emergency and take photos of the problem region within four minutes. All clinical information was successfully entered by prospective patients via DentaCom. "There are many challenges here that our app can help with," said Thyvalikakath, the paper's senior author. "It is a challenge for the patient to get the dental emergency appropriately managed, and not just treated by painkillers in a busy hospital ER by a clinician who is not a dental specialist, It is also a challenge for the dentist to get details of the problem." Corey Stein, MS, first author of the study and now a dental student at Western University of Health Sciences in California, initially conceived the idea of an app when he experienced a dental emergency. He received the American Dental Association's 2016 Robert H. Ahlstrom New Investigator Award for his work on DentaCom. Dental emergencies frequently occur when dental offices are closed. Patients often turn to hospital emergency departments or urgent care centers. But most patients who go to these facilities are simply treated for their pain and referred to their dentist for proper care during office hours. Valuable time may be lost before actual treatment is received, and the patient is billed for the emergency or urgent care visit in addition to whatever dental fees will be incurred. In contrast to a physician's office, a dentist's office is hands-on and procedure based, and it can be difficult to add an emergent patient to the schedule. The DentaCom app provides the detailed guidance that the dentist needs to determine the urgency of, and appropriately treat, the problem. "We developed this app as a communication tool linking patients and dentists during emergency situations," said Thyvalikakath, associate professor and the director of Dental Informatics Core in the IU School of Dentistry. "But I see even more potential in nonemergency situations when individuals, particularly those who lack dental insurance, need guidance -- do I need to see a dentist or not? It can also be useful in enhancing access to routine dental care." In addition to Thyvalikakath and Stein, authors of the study are Xiang Xiao, BS; Steven Levine, DMD; Titus K.L. Schleyer, DMD, PhD and Harry Hochheiser, PhD. Schleyer is now a research scientist with the Center for Biomedical Informatics at the Regenstrief Institute and is the Clem McDonald Professor of Biomedical Informatics at Indiana University School of Medicine. Xiao, Levine and Hochheiser remain at Pittsburgh. The study was funded in part by grants from the National Institutes of Health, the Lilly Endowment, the Indiana Physician Scientist Initiative and the National Library of Medicine.

CAMBRIDGE, MA and INDIANAPOLIS, IN--(Marketwired - February 09, 2017) - Elsevier, a world-leading provider of scientific, technical and medical information products and services, and the IU Richard M. Fairbanks School of Public Health at Indiana University-Purdue University Indianapolis today announced that HIMSS (Healthcare Information Management Systems Society), an international not-for-profit organization focused on better health through information technology (IT), will award its 2016 Book of the Year Award to Health Information Exchange: Navigating and Managing a Network of Health Information Systems. Edited by Brian E. Dixon, PhD, FHIMSS, an Associate Professor at the IU Richard M. Fairbanks School of Public Health and Research Scientist at the Regenstrief Institute, the book was published in March 2016 by Elsevier's Academic Press imprint. Health Information Exchange confronts the opportunities and challenges associated with the electronic exchange of data and information across the complex network of hospitals, clinics, pharmacies, and other entities involved in providing health care. While the last decade has witnessed tremendous growth in the proliferation of IT in health care, many find it complicated and frustrating to connect those systems in a way that delivers high quality, patient-centered care. Described as a "timely response to a critical need within the health system" by Charles E. Christian, FHIMSS, CHCIO, the Vice President for Technology and Engagement at the Indiana Health Information Exchange who nominated it for the award, the book chronicles the need for and progress towards interoperability among health information systems as well as the methods and tools necessary to enable seamless, nationwide exchange of health information no matter where a patient receives care. Experts and accomplished practitioners contributed to the book's chapters and its several case studies that detail how leading organizations are moving the needle with respect to health care delivery and outcomes. The HIMSS Book of the Year Award honors a book that offers outstanding practical guidance and/or strategic insight for healthcare information and management systems professionals. JoAnn W. Klinedinst, MEd, CPHIMS, PMP, DES, FHIMSS, the Vice President of Professional Development for HIMSS North America summarizes the merits of the book this way: "Not only does Dr. Dixon offer foundational knowledge on Health Information Exchange (HIE) that covers the broad areas of technology, governance, and policy but also he provides in-depth case studies that serve to connect learners to real-world applications. This combination is critical to ensuring that stakeholders across all disciplines understand the latest applications of HIE that positively impact care delivery." Editor Brian E. Dixon, PhD, FHIMSS, teaches and conducts research in the area of public health informatics, which applies information and computer science to improve population health monitoring as well as outcomes. Prior to joining the faculty at IUPUI, Dr. Dixon was an accomplished computer programmer as well as IT project manager who developed and implemented technologies that are now used by more than 100 hospitals and 20,000 physicians to exchange data necessary for caring for individual patients as well as monitoring the health of Indiana communities via the Indiana Health Information Exchange. Dr. Dixon has published more than 50 peer-reviewed publications and serves on multiple advisory boards for governmental and non-profit organizations who seek to use information technology to improve care delivery and health outcomes. Dr. Dixon was named to the "Forty Under 40" list in 2014 by the Indianapolis Business Journal and an Outstanding Investigator by the Regenstrief Institute's Center for Biomedical Informatics. He was named a HIMSS Fellow in 2012. The award will be presented to Dr. Dixon at the HIMSS Awards Gala, on February 21, 2017 at Loews Portofino Bay Hotel at Universal Orlando. The gala is one of the premier events held during the 2017 HIMSS Conference & Exhibition, from February 19-23, at the Orange County Convention Center. About the IU Richard M. Fairbanks School of Public Health The IU Richard M. Fairbanks School of Public Health at IUPUI seeks to cultivate innovative, interdisciplinary, community engaged education, research and service and prepare leaders in public health and health care. The school has over 500 students enrolled in its three undergraduate, four master's and four doctoral education programs related to public health and health administration. Pending approval, the school will offer the nation's first bachelor of science degree in health data science. The school further has numerous active research collaborations with local and state health departments in Indiana as well as the U.S. Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Agency for Healthcare Research and Quality (AHRQ), and the Robert Wood Johnson Foundation (RWJF). About Elsevier Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions -- among them ScienceDirect, Scopus, Research Intelligence and ClinicalKey -- and publishes over 2,500 journals, including The Lancet and Cell, and more than 35,000 book titles, including a number of iconic reference works. Elsevier is part of RELX Group, a world-leading provider of information and analytics for professional and business customers across industries.

News Article | November 23, 2016

INDIANAPOLIS -- Peter J. Embi, MD, MS, who joins the Regenstrief Institute as president and CEO on December 15, has been selected as the chair-elect of the board of directors of the American Medical Informatics Association, the largest international professional biomedical and health informatics association. The four-year term includes a one-year term as chair-elect, two years as the chair of the association's 21-person board of directors, and a final year as chair-emeritus. Dr. Embi is an internationally respected expert in biomedical informatics -- the application of computer and information sciences to health care and biomedical research. He has been a member of the American Medical Informatics Association since October 2000, and a board member since January 2015. In 2012 he was also inducted as a fellow of the American College of Medical Informatics, joining a select elected group of individuals who have made significant and sustained contributions to the field of biomedical informatics. "This is a critical time for health care in our country and for informatics in particular," Dr. Embi said. "As informaticians we are working to improve health care through the optimal use of information and information technology. "That couldn't be more important than it is today. We need to improve quality of care for individuals, accelerate biomedical discoveries, and keep our populations healthier. By leveraging health IT and health care data, we can better prevent, diagnose and treat disease -- with more precision and at lower cost to society - and learn from every patient to improve care well into the future. Informatics professionals are key to achieving this vision for a learning health care system." Dr. Embi notes that as a professional society, the American Medical Informatics Association is uniquely positioned to draw upon the expertise of its varied informatician membership -- physicians, nurses, pharmacists, computer scientists, technologists, physicists, biologists and others -- to determine how to optimize the use of health information technology and biomedical computing to improve health and the delivery of care. This fall he chaired the association's 2016 Annual Health Policy Invitational Meeting on health information policy. He anticipates that he, like past AMIA board chairs, will represent the association in many settings, including on Capitol Hill, and across a range of issues including electronic medical record systems, health information exchange, patient participation in their care, and accelerating biomedical research and innovation. Dr. Embi joins the Regenstrief Institute following six years at the Ohio State University, most recently as associate dean for research informatics at Ohio State's medical school. Regenstrief is recognized for pioneering work in the fields of medical informatics, aging, and health services research and for the practical application of this research to global needs -- present and future. The institute is composed of three research centers -- the William M. Tierney Center for Health Services Research, the Indiana University Center for Aging Research and the Clem McDonald Center for Biomedical Informatics. The institute's new Industry Research Office facilitates and supports industry-funded research partnerships leveraging Regenstrief's extensive resources. The institute's focal areas currently include applied health information technology, patient outcomes and safety, population and public health, precision medicine, global health informatics, brain health, health data standards, healthcare data analytics, patient outcomes, implementation science, drug safety, decision making, symptom management, nursing home care, physical fitness and health communication. Regenstrief's faculty and affiliated scientists include representatives of numerous disciplines including medical informatics, geriatrics, general internal medicine, pediatrics, family medicine, public health, emergency medicine, gastroenterology, psychiatry, neurology, sociology, global health, palliative care, communications and a variety of engineering disciplines including software and human factors engineering. In addition to his leadership position at the Regenstrief Institute, commencing next month Dr. Embi will serve as Sam Regenstrief Professor of Informatics and Health Services and as associate dean for informatics and health services research at Indiana University School of Medicine, associate director for informatics at the Indiana Clinical and Translational Sciences Institute and vice president for learning health systems at Indiana University Health.

News Article | November 22, 2016

Computer algorithms can automatically interpret echocardiographic images and distinguish between pathological hypertrophic cardiomyopathy (HCM) and physiological changes in athletes' hearts, according to research from the Icahn School of Medicine at Mount Sinai (ISMMS), published online yesterday in the Journal of the American College of Cardiology. HCM is a disease in which a portion of the myocardium enlarges, creating functional impairment of the heart. It is the leading cause of sudden death in young athletes. Diagnosing HCM is challenging since athletes can present with physiological hypertrophy, in which their hearts appear large, but do not feature the pathological abnormality of HCM. The current standard of care requires precise phenotyping of the two similar conditions by a highly trained cardiologist. "Our research has demonstrated for the first time that machine-learning algorithms can assist in the discrimination of physiological versus pathological hypertrophic remodeling, thus enabling easier and more accurate diagnoses of HCM," said senior study author Partho P. Sengupta, MD, Director of Cardiac Ultrasound Research and Professor of Medicine in Cardiology at the Icahn School of Medicine at Mount Sinai. "This is a major milestone for echocardiography, and represents a critical step toward the development of a real-time, machine-learning-based system for automated interpretation of echocardiographic images. This could help novice echo readers with limited experience, making the diagnosis rapid and more widely available." Using data from an existing cohort of 139 male subjects who underwent echocardiographic imaging at ISMMS (77 verified athlete cases and 62 verified HCM cases), the researchers analyzed the images with tissue tracking software and identified variable sets to incorporate in the machine-learning models. They then developed a collective machine-learning model with three different algorithms to differentiate the two conditions. The model demonstrated superior diagnostic ability comparable to conventional 2D echocardiographic and Doppler-derived parameters used in clinical practice. "Our approach shows a promising trend in using automated algorithms as precision medicine techniques to augment physician-guided diagnosis," said study author Joel Dudley, PhD, Director of the Institute for Next Generation Healthcare and Director of the Center for Biomedical Informatics at ISMMS. "This demonstrates how machine-learning models and other smart interpretation systems could help to efficiently analyze and process large volumes of cardiac ultrasound data, and with the growth of telemedicine, it could enable cardiac diagnoses even in the most resource-burdened areas." The team included researchers from both Dr. Sengupta's and Dr. Dudley's labs, including medical student Sukrit Narula, Khader Shameer, PhD, and Alaa Mabrouk Salem Omar, MD, PhD. The team is now in the process of developing other artificial intelligence-powered cardiovascular phenotyping algorithms to deploy to help clinicians, echocardiography technicians, and medical students to make diagnoses. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.

Matthews R.P.,Children's Hospital of Philadelphia | Eauclaire S.F.,Children's Hospital of Philadelphia | Mugnier M.,Children's Hospital of Philadelphia | Lorent K.,University of Pennsylvania | And 6 more authors.
Hepatology | Year: 2011

Infantile cholestatic disorders arise in the context of progressively developing intrahepatic bile ducts. Biliary atresia (BA), a progressive fibroinflammatory disorder of extra- and intrahepatic bile ducts, is the most common identifiable cause of infantile cholestasis and the leading indication for liver transplantation in children. The etiology of BA is unclear, and although there is some evidence for viral, toxic, and complex genetic causes, the exclusive occurrence of BA during a period of biliary growth and remodeling suggests an importance of developmental factors. Interestingly, interferon-γ (IFN-γ) signaling is activated in patients and in the frequently utilized rhesus rotavirus mouse model of BA, and is thought to play a key mechanistic role. Here we demonstrate intrahepatic biliary defects and up-regulated hepatic expression of IFN-γ pathway genes caused by genetic or pharmacological inhibition of DNA methylation in zebrafish larvae. Biliary defects elicited by inhibition of DNA methylation were reversed by treatment with glucocorticoid, suggesting that the activation of inflammatory pathways was critical. DNA methylation was significantly reduced in bile duct cells from BA patients compared to patients with other infantile cholestatic disorders, thereby establishing a possible etiologic link between decreased DNA methylation, activation of IFN-γ signaling, and biliary defects in patients. Conclusion: Inhibition of DNA methylation leads to biliary defects and activation of IFN-γ-responsive genes, thus sharing features with BA, which we determine to be associated with DNA hypomethylation. We propose epigenetic activation of IFN-γ signaling as a common etiologic mechanism of intrahepatic bile duct defects in BA. © 2010 American Association for the Study of Liver Diseases.

Stockwell M.S.,Columbia University | Stockwell M.S.,New York Presbyterian Hospital | Fiks A.G.,Pediatric Research Consortium PeRC | Fiks A.G.,Center for Biomedical Informatics | And 3 more authors.
Human Vaccines and Immunotherapeutics | Year: 2013

Vaccination coverage is still below the Healthy People 2010 and 2020 goals. Technology use in the US is widespread by patients and providers including text message, email, internet, social media and electronic health records. Health information technology (IT) interventions can facilitate the rapid or real-time identification of children in need of vaccination and provide the foundation for vaccine-oriented parental communication or clinical alerts in a flexible and tailored manner. There has been a small but burgeoning field of work integrating IT into vaccination interventions including reminder/recall using nontraditional methods, clinical decision support for providers in the electronic health record, use of technology to affect workflow and the use of social media. The aim of this review is to introduce and present current data regarding the effectiveness of a range of technology tools to promote vaccination, describe gaps in the literature and offer insights into future directions for research and intervention. © 2013 Landes Bioscience.

News Article | October 4, 2016

University of Arizona research assistant professor and immunologist Adam Buntzman used CyVerse data-sharing and analysis capabilities to lead the first team to comprehensively map the human adaptive immune system. Knowing the full potential for our immune systems to protect us from harmful pathogens brings us one huge step closer to finding cures for illnesses such as cancer, infections, autoimmune diabetes and asthma, as well as developing improved diagnostic tests and immune therapies. "Understanding adaptive immunity is one of the grand challenges in science," said Yves Lussier, associate vice president for UA Health Sciences and executive director of the UA Center for Biomedical Informatics and Biostatics. "The unique genetics and massive diversity that occur exclusively in cells of the adaptive immune system has posed a dire need for computer tools created specifically to analyze adaptive immune receptors." Now Buntzman and his collaborators have combined the expertise of immunologists, mathematicians and computer scientists to develop these much-needed computational tools. "If we were on a treasure hunt, where the cure to many illnesses is the buried treasure, then we've just drawn the first map of Treasure Island," said Buntzman, an investigator in the lab of Monica Kraft, a physician-scientist specializing in research of dysfunctional autoimmune response in asthma and chair of the UA Department of Medicine. More Complex Than the Human Genome The adaptive immune system is perhaps the most mysterious — and certainly one of the most vital — systems of the human body, protecting us from everything from common cold germs to serious infections. Cells within the human adaptive immune system produce antibodies and T-cell receptors that identify and remove harmful foreign substances from the body. Unfortunately, the immune system can become a powerful enemy when it misidentifies a part of the body as pathogenic, leading to autoimmune diseases, or when it overreacts to foreign materials such as pollen, resulting in allergies such as asthma. The immune system is considered to be "adaptive" because it can respond to our unique environments. Once it has overcome a particular pathogen, the immune system will "remember" and quickly destroy that pathogen if it ever enters our bodies again, thus giving us immunity. Adaptive immune systems also vary from one person to the next, providing immunity depending upon what microbes an individual has been exposed to throughout their lifetime. "Humans have about 25,000 genes in our genome, but there are millions of harmful microbes, which begs the question: How does such a small number of genes code for all of the immune receptors needed to recognize the enormous array of microbes that can hurt us?" Buntzman said. It turns out that immune receptor genes do not code for immune receptors; rather, broken gene fragments combine in novel ways to produce new code. Every time a new antibody or T-cell receptor is created, the adaptive immune system "shuffles the deck" of gene fragments, blending together the broken pieces through a process called VDJ Recombination. "These gene fragments are then modified by enzymes, creating a dizzying array of variation," Buntzman said. The possible variation of immune receptors far exceeds the number of genes in our genome, at roughly 10 million times more than the number of stars in the Milky Way galaxy, he noted. That's also about 100-fold the number of ants on Earth. And therein lies the complication. "How do we study this much diversity? How do we find which receptors cause autoimmune disorders, and which receptors protect us from influenza?" Buntzman said. Genome sequencing instruments have addressed the problem yet remain incapable of handling the enormity of data. Until now. Just as genomics involves sequencing whole genomes, the field of immunomics involves mapping sequences of immune receptors — a mathematical challenge given that the human adaptive immune system swamps the diversity of most genomics studies. Buntzman calculated that using traditional computational methods to generate a complete genetic map of the immunome — all possible receptors the immune system might generate — would take roughly 106 years. "Waiting that long is clearly impractical," he said, "but this is where CyVerse comes in." Headquartered at the UA's BIO5 Institute, CyVerse is a National Science Foundation-funded project to provide computational infrastructure for big-data problems in the life sciences. Buntzman began working with CyVerse collaborator Ali Akoglu of the UA College of Engineering to develop computational tools to map the immunome using high-performance computing, or HPC, techniques. With access to HPC technology and support through CyVerse, Buntzman, Akoglu and Akoglu's graduate student Gregory Striemer developed a program to run the analysis in under 17 days on a computer chip housed inside a simple laptop. "My role was to restructure the algorithm to accelerate the results," Akoglu said. "This was the first study to generate and process terabytes of data exhaustively, going through all possible combinations of sequences, and in a relatively short amount of time. And CyVerse was the catalyzer that brought us together." Armed with the power of computation, Buntzman and his colleagues have developed a software tool capable of comprehensively mapping the adaptive immune system without limitation, and a computer program that is a community-accessible utility to database these complex immunome datasets, as described at the 2016 conference of the American Association of Immunologists and in an upcoming publication to be released in the journal BMC Bioinformatics. In addition, Buntzman's group has developed another computer program to run a novel algorithm called iWAS, or immunome-Wide Association Study, that can mine the immunome for patterns of immune receptors responsible for protecting us from specific diseases or causing autoimmune disorders. Understanding the role of individual immune receptors could pave the way to developing advanced therapies, potentially revolutionizing the field of adaptive immunity. "This work will aid in the study of cancer, autoimmunity, transplantation and vaccination, and assist in developing new precision medical diagnostics and patient-centered immunotherapies, as well as identify biomarkers for inflammatory diseases," Lussier said. "By working across disciplines as immunologists, mathematicians and computer scientists," he said, "we were able to tackle a problem that was untenable to any discipline alone. We've created an analytical infrastructure with CyVerse that allows for all the data to be stored and analyzed by researchers everywhere."

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