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Patrick Schloss

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The Schloss lab is broadly interested in beneficial and pathogenic host-microbiome interactions with the goal of improving our understanding of how the microbiome can be used to reach translational outcomes in the prevention, detection, and treatment of colorectal cancer, Crohn’s disease, and Clostridium difficile infection. To address these questions, we test traditional ecological theory in the microbial context using a systems biology approach. Specifically, the laboratory specializes in using studies involving human subjects and animal models to understand how biological diversity affects community function using a variety of culture-independent genomics techniques including sequencing 16S rRNA gene fragments, metagenomics, and metatranscriptomics. In addition, they use metabolomics to understand the functional role of the gut microbiota in states of health and disease. To support these efforts, they develop and apply bioinformatic tools to facilitate their analysis. Most notable is the development of the mothur software package (https://www.mothur.org), which is one of the most widely used tools for analyzing microbiome data and has been cited more than 7,300 times since it was initially published in 2009. The Schloss lab deftly merges the ability to collect data to answer important biological questions using cutting edge wet-lab techniques and computational tools to synthesize these data to answer their biological questions.

Given the explosion in microbiome research over the past 15 years, the Schloss lab has also stood at the center of a major effort to train interdisciplinary scientists in applying computational tools to study complex biological systems. These efforts have centered around developing reproducible research skills and applying modern data visualization techniques. An outgrowth of these efforts at the University of Michigan has been the institutionalization of The Carpentries organization on campus (https://carpentries.org), which specializes in peer-to-peer instruction of programming tools and techniques to foster better reproducibility and build a community of practitioners.

The Schloss lab uses computational tools to integrate multi-omics tools in a culture-independent approach to understand how bacteria interact with each other and their host to drive processes such as colorectal cancer and susceptibility to Clostridium difficile infections.

Áine Heneghan

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Professor Heneghan’s research interests include music analysis, study of archival documents, the history of music theory, and the Second Viennese School. Her new research project examines the corpus of piping tunes collected by James Goodman in south-west Ireland during the mid-1800s. Funded by MIDAS, this work is part of a larger project with colleagues in music theory, statistics, and linguistics entitled “A Computational Study of Patterned Melodic Structures across Musical Cultures.”

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.

 

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.

    Danny Forger

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    Daniel Forger is a Professor in the Department of Mathematics. He is devoted to understanding biological clocks. He uses techniques from many fields, including computer simulation, detailed mathematical modeling and mathematical analysis, to understand biological timekeeping. His research aims to generate predictions that can be experimentally verified.

    Peter Adriaens

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    My research focus is on the development and application of machine learning tools to large scale financial and unstructured (textual) data to extract, quantify and predict risk profiles and investment grade rating of private and public companies.  Example datasets include social media and financial aggregators such as Bloomberg, Pitchbook, and Privco.

    Suleyman Uludag

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    My research spans security, privacy, and optimization of data collection particularly as applied to the Smart Grid, an augmented and enhanced paradigm for the conventional power grid. I am particularly interested in optimization approaches that take a notion of security and/or privacy into the modeling explicitly. At the intersection of the Intelligent Transportation Systems, Smart Grid, and Smart Cities, I am interested in data privacy and energy usage in smart parking lots. Protection of data and availability, especially under assault through a Denial-of-Service attacks, represents another dimension of my area of research interests. I am working on developing data privacy-aware bidding applications for the Smart Grid Demand Response systems without relying on trusted third parties. Finally, I am interested in educational and pedagogical research about teaching computer science, Smart Grid, cyber security, and data privacy.

    This figure shows the data collection model I used in developing a practical and secure Machine-to-Machine data collection protocol for the Smart Grid.

    This figure shows the data collection model I used in developing a practical and secure
    Machine-to-Machine data collection protocol for the Smart Grid.

    Necmiye Ozay

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    Necmiye Ozay, PhD, is Assistant Professor of Electrical Engineering and Computer Science, College of Engineering, at the University of Michigan, Ann Arbor.

    Prof. Ozay and her team develop the scientific foundations and associated algorithmic tools for compactly representing and analyzing heterogeneous data streams from sensor/information-rich networked dynamical systems. They take a unified dynamics-based and data-driven approach for the design of passive and active monitors for anomaly detection in such systems. Dynamical models naturally capture temporal (i.e., causal) relations within data streams. Moreover, one can use hybrid and networked dynamical models to capture, respectively, logical relations and interactions between different data sources. They study structural properties of networks and dynamics to understand fundamental limitations of anomaly detection from data. By recasting information extraction problem as a networked hybrid system identification problem, they bring to bear tools from computer science, system and control theory and convex optimization to efficiently and rigorously analyze and organize information. The applications include diagnostics, anomaly and change detection in critical infrastructure such as building management systems, transportation and energy networks.