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Ho-Joon Lee

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Dr. Lee’s research in data science concerns biological questions in systems biology and network medicine by developing algorithms and models through a combination of statistical/machine learning, information theory, and network theory applied to multi-dimensional large-scale data. His projects have covered genomics, transcriptomics, proteomics, and metabolomics from yeast to mouse to human for integrative analysis of regulatory networks on multiple molecular levels, which also incorporates large-scale public databases such as GO for functional annotation, PDB for molecular structures, and PubChem and LINCS for drugs or small compounds. He previously carried out proteomics and metabolomics along with a computational derivation of dynamic protein complexes for IL-3 activation and cell cycle in murine pro-B cells (Lee et al., Cell Reports 2017), for which he developed integrative analytical tools using diverse approaches from machine learning and network theory. His ongoing interests in methodology include machine/deep learning and topological Kolmogorov-Sinai entropy-based network theory, which are applied to (1) multi-level dynamic regulatory networks in immune response, cell cycle, and cancer metabolism and (2) mass spectrometry-based omics data analysis.

Figure 1. Proteomics and metabolomics analysis of IL-3 activation and cell cycle (Lee et al., Cell Reports 2017). (A) Multi-omics abundance profiles of proteins, modules/complexes, intracellular metabolites, and extracellular metabolites over one cell cycle (from left to right columns) in response to IL-3 activation. Red for proteins/modules/intracellular metabolites up-regulation or extracellular metabolites release; Green for proteins/modules/intracellular metabolites down-regulation or extracellular metabolites uptake. (B) Functional module network identified from integrative analysis. Red nodes are proteins and white nodes are functional modules. Expression profile plots are shown for literature-validated functional modules. (C) Overall pathway map of IL-3 activation and cell cycle phenotypes. (D) IL-3 activation and cell cycle as a cancer model along with candidate protein and metabolite biomarkers. (E) Protein co-expression scale-free network. (F) Power-low degree distribution of the network E. (G) Protein entropy distribution by topological Kolmogorov-Sinai entropy calculated for the network E.

 

Tim Cernak

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Tim Cernak, PhD, is Assistant Professor of Medicinal Chemistry with secondary appointments in Chemistry and the Chemical Biology Program at the University of Michigan, Ann Arbor.

The functional and biological properties of a small molecule are encoded within its structure so synthetic strategies that access diverse structures are paramount to the invention of novel functional molecules such as biological probes, materials or pharmaceuticals. The Cernak Lab studies the interface of chemical synthesis and computer science to understand the relationship of structure, properties and reactions. We aim to use algorithms, robotics and big data to invent new chemical reactions, synthetic routes to natural products, and small molecule probes to answer questions in basic biology. Researchers in the group learn high-throughput chemical and biochemical experimentation, basic coding, and modern synthetic techniques. By studying the relationship of chemical synthesis to functional properties, we pursue the opportunity to positively impact human health.

Samuel K Handelman

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Samuel K Handelman, Ph.D., is Research Assistant Professor in the department of Internal Medicine, Gastroenterology, of Michigan Medicine at the University of Michigan, Ann Arbor. Prof. Handelman is focused on multi-omics approaches to drive precision/personalized-therapy and to predict population-level differences in the effectiveness of interventions. He tends to favor regression-style and hierarchical-clustering approaches, partially because he has a background in both statistics and in cladistics. His scientific monomania is for compensatory mechanisms and trade-offs in evolution, but he has a principled reason to focus on translational medicine: real understanding of these mechanisms goes all the way into the clinic. Anything less that clinical translation indicates that we don’t understand what drove the genetics of human populations.

Zhenke Wu

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Zhenke Wu is an Assistant Professor of Biostatistics, and a core faculty member in the Michigan Institute of Data Science (MIDAS). He received his Ph.D. in Biostatistics from the Johns Hopkins University in 2014 and then stayed at Hopkins for his postdoctoral training before joining the University of Michigan. Dr. Wu’s research focuses on the design and application of statistical methods that inform health decisions made by individuals, or precision medicine. The original methods and software developed by Dr. Wu are now used by investigators from research institutes such as CDC and Johns Hopkins, as well as site investigators from developing countries, e.g., Kenya, South Africa, Gambia, Mali, Zambia, Thailand and Bangladesh.

 

Profile: At a “sweet spot” of data science

By Dan Meisler
Communications Manager, ARC

If you had to name two of the more exciting, emerging fields of data science, electronic health records (EHR) and mobile health might be near the top of the list.

Zhenke Wu, one of the newest MIDAS core faculty members, has one foot firmly in each field.

“These two fields share the common goal of learning from the experience of the population in the past to advance health and clinical decisions for those to follow. I am looking forward to more work that will bring the two fields closer to continuously generate insights about human health.” Wu said. “I’m in a sweet spot.”

Wu joined U-M in Fall 2016, after earning a PhD in Biostatistics from Johns Hopkins University, and a bachelor’s in Mathematics from Fudan University. He said the multitude of large-scale studies going on at U-M and access to EHR databases were factors in his coming to Michigan.

“The University of Michigan is an exciting place that has a diversity of large-scale databases and supportive research groups in the fields I’m interested in,” he said.

Wu is collaborating with the Michigan Genomics Initiative, which is a biorepository effort at Michigan Medicine to integrate genome-wide information with EHR from approximately 40,000 patients undergoing anesthesia prior to surgery or diagnostic procedures. He’s also collaborating with Dr. Srijan Sen, Associate Professor, Department of Psychiatry and Molecular and Behavioral Neuroscience Institute, on the MIDAS-supported project “Identifying Real-Time Data Predictors of Stress and Depression Using Mobile Technology,” the preliminary results of which recently matured into an NIH-funded R01 project “Mobile Technology to Identify Mechanisms Linking Genetic Variation and Depression” that will draw broad expertise from a multi-disciplinary team of medical and data science researchers.

A visualization of data from the Michigan Genomics Initiative

“One of my goals is to use an integrated and rigorous approach to predict how a person’s health status will be in the near future,” Wu said.

Wu applies hierarchical Bayesian models to these problems, which he hopes will shed light on phenomena he describes as latent constructs that are “well-known, but less quantitatively understood, e.g., intelligence quotient (IQ) in psychology.”

As another example, he cites the current challenge in active surveillance of prostate cancer patients for aggressive tumors requiring removal and/or radiation, or indolent tumors permitting continued surveillance.

“The underlying status of aggressive versus indolent cancer is not observed, which needs to be learned from the results of biopsy and other clinical measurements,” he said. “The decisions and experience of urologists and their patients will greatly benefit from more accurate understanding of the tumor status… There are lots of scientific problems in clinical, biomedical, behavioral and social sciences where you have well-known but less quantitatively understood latent constructs. These are problems that Bayesian latent variable methods can formulate and address.”

Just as Wu has a hand in two hot-button big data areas, he also sees himself as straddling the line between application and methodology.

He says the large number of data sources — sensors, mobile apps, test results, and questionnaires, to name just a few — results in richness as well as some “messiness” that needs new methodologies to adjust, integrate and translate to new scientific insights. At the same time, a valid new methodology for dealing with, for example, electronic health data, will likely find numerous different applications.

Wu says his approach was heavily influenced by his work in the Pneumonia Etiology Research for Child Health (PERCH) funded by the Gates Foundation while he was at Johns Hopkins. Pneumonia is a clinical syndrome due to lung infection that can be caused by more than 30 different species of pathogens, including bacteria, viruses and fungi. The goal of the seven-country study that enrolled more than 5,000 cases and 5,000 controls from Africa and Southeast Asia is to estimate the frequency with which each pathogen caused pneumonia in the population and the probability of each individual being infected by the list of pathogens in the lung.

“In most settings, it is extremely difficult to identify the pathogen by directly sampling from the site of infection – the child’s lung. PERCH therefore looked for other sources of evidence by standardizing and comprehensively testing biofluids collected from sites peripheral to the lung. Using hierarchical Bayesian models to infer disease etiology by integrating such a large trove of data was extremely fun and exciting”, he said.

Wu’s initial interest in math, leading to biostatistics and now data science, stems from what he called a “greedy” desire to learn the guiding principles of how the world works by rigorous data science.

“If you have new problems, you can wait for other people to ask a clean math question, or you can go work with these messy problems and figure out interesting questions and their answers,” he said.

For more on Dr. Wu, see his profile on Michigan Experts.

Recent publications

From experts.umich.edu.

    V. G. Vinod Vydiswaran

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    V.G.Vinod Vydiswaran, PhD, is Assistant Professor in the Department of Learning Health Sciences with a secondary appointment in the School of Information at the University of Michigan, Ann Arbor.

    Dr. Vydiswaran’s research focuses on developing and applying text mining, natural language processing, and machine learning methodologies for extracting relevant information from health-related text corpora. This includes medically relevant information from clinical notes and biomedical literature, and studying the information quality and credibility of online health communication (via health forums and tweets). His previous work includes developing novel information retrieval models to assist clinical decision making, modeling information trustworthiness, and addressing the vocabulary gap between health professionals and  laypersons.

    Andrzej T Galecki

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    Andrzej Galecki, MD, PhD, is Research Professor in the department of Biostatistics, School of Public Health, and Research Professor in the Institute of Gerontology at the University of Michigan, Ann Arbor.

    Romesh P. Nalliah

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    Dr. Nalliah’s research expertise is process evaluation. He has studied various healthcare processes, educational processes and healthcare economics. Dr. Nalliah’s research studies were the first time nationwide data was used to highlight emergency room resource utilization for managing dental conditions in the United States. Dr. Nalliah is internationally recognized as a pioneer in the field of nationwide hospital dataset research for dental conditions and has numerous publications in peer reviewed journals. After completing a masters degree at Harvard School of Public Health, Dr. Nalliah’s interests have expanded and he has studied various public health issues including sports injuries, poisoning, child abuse, motor vehicle accidents and surgical processes (like stem cell transplants, cardiac valve surgery and fracture reduction). National recognition of his expertise in these broader topics of medicine have given rise to opportunities to lecture to medical residents, nurse practitioners, students in medical, pharmacy and nursing programs about oral health. This is his passion- that his research should inform an evolution of health education curriculum and practice.

    Dr. Nalliah’s professional mission is to improve healthcare delivery systems and he is interested in improving processes, minimizing inefficiencies, reducing healthcare bottlenecks, increasing quality, and increase task sharing which will lead to a patient-centered, coherent healthcare system. Dr. Nalliah’s research has identified systems constraints and his goal is to influence policy and planning to break those constraints and improve healthcare delivery.

    Gilbert S. Omenn

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    Gilbert Omenn, MD, PhD, is Professor of Computational Medicine & Bioinformatics with appointments in Human Genetics, Molecular Medicine & Genetics in the Medical School and Professor of Public Health in the School of Public Health and the Harold T. Shapiro Distinguished University Professor at the University of Michigan, Ann Arbor.

    Doctor Omenn’s current research interests are focused on cancer proteomics, splice isoforms as potential biomarkers and therapeutic tar- gets, and isoform-level and single-cell functional networks of transcripts and proteins. He chairs the global Human Proteome Project of the Human Proteome Organization.

    Omid Dehzangi

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    Omid Dehzangi, PhD, is Assistant Professor of Computer and Information Science, College of Engineering and Computer Science, at the University of Michigan, Dearborn.

    Wearable health technology is drawing significant attention for good reasons. The pervasive nature of such systems providing ubiquitous access to the continuous personalized data will transform the way people interact with each other and their environment. The resulting information extracted from these systems will enable emerging applications in healthcare, wellness, emergency response, fitness monitoring, elderly care support, long-term preventive chronic care, assistive care, smart environments, sports, gaming, and entertainment which create many new research opportunities and transform researches from various disciplines into data science which is the methodological terminology for data collection, data management, data analysis, and data visualization. Despite the ground-breaking potentials, there are a number of interesting challenges in order to design and develop wearable medical embedded systems. Due to limited available resources in wearable processing architectures, power-efficiency is demanded to allow unobtrusive and long-term operation of the hardware. Also, the data-intensive nature of continuous health monitoring requires efficient signal processing and data analytic algorithms for real-time, scalable, reliable, accurate, and secure extraction of relevant information from an overwhelmingly large amount of data. Therefore, extensive research in their design, development, and assessment is necessary. Embedded Processing Platform Design The majority of my work concentrates on designing wearable embedded processing platforms in order to shift the conventional paradigms from hospital-centric healthcare with episodic and reactive focus on diseases to patient-centric and home-based healthcare as an alternative segment which demands outstanding specialized design in terms of hardware design, software development, signal processing and uncertainty reduction, data analysis, predictive modeling and information extraction. The objective is to reduce the costs and improve the effectiveness of healthcare by proactive early monitoring, diagnosis, and treatment of diseases (i.e. preventive) as shown in Figure 1.

    Figure 1. Embedded processing platform in healthcare

    Jieping Ye

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    Jieping Ye, PhD, is Associate Professor of Computational Medicine and Bioinformatics in the Medical School at the University of Michigan, Ann Arbor.

    The Ye Lab has been conducting fundamental research in machine learning and data mining, developing computational methods for biomedical data analysis, and building informatics software. We have developed novel machine learning algorithms for feature extraction from high-dimensional data, sparse learning, multi-task learning, transfer learning, active learning, multi-label classification, and matrix completion. We have developed the SLEP (Sparse Learning with Efficient Projections) package, which includes implementations of large-scale sparse learning models, and the MALSAR (Multi-tAsk Learning via StructurAl Regularization) package, which includes implementations of state-of-the-art multi-task learning models. SLEP achieves state-of-the-art performance for many sparse learning models, and it has become one of the most popular sparse learning software packages. With close collaboration with researchers at the biomedical field, we have successfully applied these methods for analyzing biomedical data, including clinical image data and genotype data.