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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.

 

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.

Yang Chen

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Yang Chen received her Ph.D. (2017) in Statistics from Harvard University and then joined the University of Michigan as an Assistant Professor of Statistics and Research Assistant Professor at the Michigan Institute of Data Science (MIDAS). She received her B.A. in Mathematics and Applied Mathematics from the University of Science and Technology of China. Research interests include computational algorithms in statistical inference and applied statistics in the field of biology and astronomy.

Jun Li

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Jun Li, PhD, is Professor and Chair for Research in the department of Computational Medicine and Bioinformatics and Professor of Human Genetics in the Medical School at the University of Michigan, Ann Arbor.

 Prof. Li’s areas of interest include genetic and genomic analyses of complex phenotypes, including bipolar disorder, cancer, blood clotting disease, and traits involving animal models and human microbiomes. Our approach emphasizes statistical analysis of genome-scale datasets (e.g, gene expression and genotyping data, results from next-generation sequencing), evolutionary history, bioinformatics, and pattern recognition.

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.

Brenda Gillespie

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Brenda Gillespie, PhD, is Associate Director in Consulting for Statistics, Computing and Analytics Research (CSCAR) with a secondary appointment as Associate Research Professor in the department of Biostatistics in the School of Public Health at the University of Michigan, Ann Arbor. She provides statistical collaboration and support for numerous research projects at the University of Michigan. She teaches Biostatistics courses as well as CSCAR short courses in survival analysis, regression analysis, sample size calculation, generalized linear models, meta-analysis, and statistical ethics. Her major areas of expertise are clinical trials and survival analysis.

Prof. Gillespie’s research interests are in the area of censored data and clinical trials. One research interest concerns the application of categorical regression models to the case of censored survival data. This technique is useful in modeling the hazard function (instead of treating it as a nuisance parameter, as in Cox proportional hazards regression), or in the situation where time-related interactions (i.e., non-proportional hazards) are present. An investigation comparing various categorical modeling strategies is currently in progress.

Another area of interest is the analysis of cross-over trials with censored data. Brenda has developed (with M. Feingold) a set of nonparametric methods for testing and estimation in this setting. Our methods out-perform previous methods in most cases.

Sriram Chandrasekaran

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Sriram Chandrasekaran, PhD, is Assistant Professor of Biomedical Engineering in the College of Engineering at the University of Michigan, Ann Arbor.

Dr. Chandrasekaran’s Systems Biology lab develops computer models of biological processes to understand them holistically. Sriram is interested in deciphering how thousands of proteins work together at the microscopic level to orchestrate complex processes like embryonic development or cognition, and how this complex network breaks down in diseases like cancer. Systems biology software and algorithms developed by his lab are highlighted below and are available at http://www.sriramlab.org/software/.

– INDIGO (INferring Drug Interactions using chemoGenomics and Orthology) algorithm predicts how antibiotics prescribed in combinations will inhibit bacterial growth. INDIGO leverages genomics and drug-interaction data in the model organism – E. coli, to facilitate the discovery of effective combination therapies in less-studied pathogens, such as M. tuberculosis. (Ref: Chandrasekaran et al. Molecular Systems Biology 2016)

– GEMINI (Gene Expression and Metabolism Integrated for Network Inference) is a network curation tool. It allows rapid assessment of regulatory interactions predicted by high-throughput approaches by integrating them with a metabolic network (Ref: Chandrasekaran and Price, PloS Computational Biology 2013)

– ASTRIX (Analyzing Subsets of Transcriptional Regulators Influencing eXpression) uses gene expression data to identify regulatory interactions between transcription factors and their target genes. (Ref: Chandrasekaran et al. PNAS 2011)

– PROM (Probabilistic Regulation of Metabolism) enables the quantitative integration of regulatory and metabolic networks to build genome-scale integrated metabolic–regulatory models (Ref: Chandrasekaran and Price, PNAS 2010)

 

Research Overview: We develop computational algorithms that integrate omics measurements to create detailed genome-scale models of cellular networks. Some clinical applications of our algorithms include finding metabolic vulnerabilities in pathogens (M. tuberculosis) using PROM, and designing multi combination therapeutics for reducing antibiotic resistance using INDIGO.

Research Overview: We develop computational algorithms that integrate omics measurements to create detailed genome-scale models of cellular networks. Some clinical applications of our algorithms include finding metabolic vulnerabilities in pathogens (M. tuberculosis) using PROM, and designing multi combination therapeutics for reducing antibiotic resistance using INDIGO.

Yuekai Sun

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Yuekai Sun, PhD, is Assistant Professor in the department of Statistics at the University of Michigan, Ann Arbor.

Dr. Sun’s research is motivated by the challenges of analyzing massive data sets in data-driven science and engineering. I focus on statistical methodology for high-dimensional problems; i.e. problems where the number of unknown parameters is comparable to or exceeds the sample size. My recent work focuses on two problems that arise in learning from high-dimensional data (versus black-box approaches that do not yield insights into the underlying data-generation process). They are:
1. model selection and post-selection inference: discover the latent low-dimensional structure in high-dimensional data and perform inference on the learned structure;
2. distributed statistical computing: design scalable estimators and algorithms that avoid communication and minimize “passes” over the data.
A recurring theme in my work is exploiting the geometry of latent low-dimensional structure for statistical and computational gains. More broadly, I am interested in the geometric aspects of high-dimensional data analysis.

A visualization of an algorithm for making accurate recommendations from data that contain shared user accounts.

A visualization of an algorithm for making accurate recommendations from data that contain shared user accounts.

 

Adriene Beltz

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The goal of my research is to leverage network analysis techniques to uncover how the brain mediates sex hormone influences on gendered behavior across the lifespan. Specifically, my data science research concerns the creation and application of person-specific connectivity analyses, such as unified structural equation models, to time series data; these are intensive longitudinal data, including functional neuroimages, daily diaries, and observations. I then use these data science methods to investigate the links between androgens (e.g., testosterone) and estradiol at key developmental periods, such as puberty, and behaviors that typically show sex differences, including aspects of cognition and psychopathology.

A network map showing the directed connections among 25 brain regions of interest in the resting state frontoparietal network for an individual; data were acquired via functional magnetic resonance imaging. Black lines depict connections common across individuals in the sample, gray lines depict connections specific to this individual, solid lines depict contemporaneous connections (occurring in the same volume), and dashed lines depict lagged connections (occurring between volumes).

A network map showing the directed connections among 25 brain regions of interest in the resting state frontoparietal network for an individual; data were acquired via functional magnetic resonance imaging. Black lines depict connections common across individuals in the sample, gray lines depict connections specific to this individual, solid lines depict contemporaneous connections (occurring in the same volume), and dashed lines depict lagged connections (occurring between volumes).

Nils G. Walter

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Nils G. Walter, PhD, is the Francis S. Collins Collegiate Professor of Chemistry, Biophysics and Biological Chemistry, College of Literature, Science, and the Arts and Professor of Biological Chemistry, Medical School, at the University of Michigan, Ann Arbor.

Nature and Nanotechnology likewise employ nanoscale machines that self-assemble into structures of complex architecture and functionality.  Fluorescence microscopy offers a non-invasive tool to probe and ultimately dissect and control these nanoassemblies in real-time.  In particular, single molecule fluorescence resonance energy transfer (smFRET) allows us to measure distances at the 2-8 nm scale, whereas complementary super-resolution localization techniques based on Gaussian fitting of imaged point spread functions (PSFs) measure distances in the 10 nm and longer range.  In terms of Big Data Analysis, we have developed a method for the intracellular single molecule, high-resolution localization and counting (iSHiRLoC) of microRNAs (miRNAs), a large group of gene silencers with profound roles in our body, from stem cell development to cancer.  Microinjected, singly-fluorophore labeled, functional miRNAs are tracked at super-resolution within individual diffusing particles.  Observed mobility and mRNA dependent assembly changes suggest the existence of two kinetically distinct assembly processes.  We are currently feeding these data into a single molecule systems biology pipeline to bring into focus the unifying molecular mechanism of such a ubiquitous gene regulatory pathway.  In addition, we are using cluster analysis of smFRET time traces to show that large RNA processing machines such as single spliceosomes – responsible for the accurate removal of all intervening sequences (introns) in pre-messenger RNAs – are working as biased Brownian ratchet machines.  On the opposite end of the application spectrum, we utilize smFRET and super-resolution fluorescence microscopy to monitor enhanced enzyme cascades and nanorobots engineered to self-assemble and function on DNA origami.

Artistic depiction of the SiMREPS platform we are building for the direct single molecule counting of miRNA biomarkers in crude biofluids (Johnson-Buck, A. et al. Kinetic fingerprinting to identify and count single nucleic acids. Nat Biotechnol 33, 730-732 (2015)).

Artistic depiction of the SiMREPS platform we are building for the direct single molecule counting of miRNA biomarkers in crude biofluids (Johnson-Buck, A. et al. Kinetic fingerprinting to identify and count single nucleic acids. Nat Biotechnol 33, 730-732 (2015)).