Jian Kang

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Dr. Kang’s research focuses on the developments of statistical methods motivated by biomedical applications with a focus on neuroimaging. His recent key contributions can be summarized in the following three aspects:

Bayesian regression for complex biomedical applications
Dr. Kang and his group developed a series of Bayesian regression methods for the association analysis between the clinical outcome of interests (disease diagnostics, survival time, psychiatry scores) and the potential biomarkers in biomedical applications such as neuroimaging and genomics. In particular, they developed a new class of threshold priors as compelling alternatives to classic continuous shrinkages priors in Bayesian literatures and widely used penalization methods in frequentist literatures. Dr. Kang’s methods can substantially increase the power to detect weak but highly dependent signals by incorporating useful structural information of predictors such as spatial proximity within brain anatomical regions in neuroimaging [Zhao et al 2018; Kang et al 2018, Xue et al 2019] and gene networks in genomics [Cai et al 2017; Cai et al 2019]. Dr Kang’s methods can simultaneously select variables and evaluate the uncertainty of variable selection, as well as make inference on the effect size of the selected variables. His works provide a set of new tools for biomedical researchers to identify important biomarkers using different types of biological knowledge with statistical guarantees. In addition, Dr. Kang’s work is among the first to establish rigorous theoretical justifications for Bayesian spatial variable selection in imaging data analysis [Kang et al 2018] and Bayesian network marker selection in genomics [Cai et al 2019]. Dr. Kang’s theoretical contributions not only offer a deep understanding of the soft-thresholding operator on smooth functions, but also provide insights on which types of the biological knowledge may be useful to improve biomarker detection accuracy.

Prior knowledge guided variable screening for ultrahigh-dimensional data
Dr. Kang and his colleagues developed a series of variable screening methods for ultrahigh-dimensional data analysis by incorporating the useful prior knowledge in biomedical applications including imaging [Kang et al 2017, He et al 2019], survival analysis [Hong et al 2018] and genomics [He et al 2019]. As a preprocessing step for variable selection, variable screening is a fast-computational approach to dimension reduction. Traditional variable screening methods overlook useful prior knowledge and thus the practical performance is unsatisfying in many biomedical applications. To fill this gap, Dr. Kang developed a partition-based ultrahigh-dimensional variable screening method under generalized linear model, which can naturally incorporate the grouping and structural information in biomedical applications. When prior knowledge is unavailable or unreliable, Dr. Kang proposed a data-driven partition screening framework on covariate grouping and investigate its theoretical properties. The two special cases proposed by Dr. Kang: correlation-guided partitioning and spatial location guided partitioning are practically extremely useful for neuroimaging data analysis and genome-wide association analysis. When multiple types of grouping information are available, Dr. Kang proposed a novel theoretically justified strategy for combining screening statistics from various partitioning methods. It provides a very flexible framework for incorporating different types of prior knowledge.

Brain network modeling and inferences
Dr. Kang and his colleagues developed several new statistical methods for brain network modeling and inferences using resting-state fMRI data [Kang et al 2016, Xie and Kang 2017, Chen et al 2018]. Due to the high dimensionality of fMRI data (over 100,000 voxels in a standard brain template) with small sample sizes (hundreds of participants in a typical study), it is extremely challenging to model the brain functional connectivity network at voxel-levels. Some existing methods model brain anatomical region-level networks using the region-level summary statistics computed from voxel-level data. Those methods may suffer low power to detect the signals and have an inflated false positive rate, since the summary statistics may not well capture the heterogeneity within the predefined brain regions. To address those limitations, Dr. Kang proposed a novel method based on multi-attribute canonical correlation graphs [Kang et al 2016] to construct region-level brain network using voxel-level data. His method can capture different types of nonlinear dependence between any two brain regions consisting of hundreds or thousands of voxels. He also developed permutation tests for assessing the significance of the estimated network. His methods can largely increase power to detect signals for small sample size problems. In addition, Dr. Kang and his colleague also developed theoretically justified high-dimensional tests [Xie and Kang 2017] for constructing region-level brain networks using the voxel-level data under the multivariate normal assumption. Their theoretical results provide a useful guidance for the future development of statistical methods and theory for brain network analysis.

 

This image illustrates the neuroimaging meta-analysis data (Kang etal 2014). Neuroimaging meta-analysis is an important tool for finding consistent effects over studies. We develop a Bayesian nonparametric model and perform a meta-analysis of five emotions from 219 studies. In addition, our model can make reverse inference by using the model to predict the emotion type from a newly presented study. Our method outperforms other methods with an average of 80% accuracy.

1. Cai Q, Kang J, Yu T (2020) Bayesian variable selection over large scale networks via the thresholded graph Laplacian Gaussian prior with application to genomics. Bayesian Analysis, In Press (Earlier version won a student paper award from Biometrics Section of the ASA in JSM 2017)
2. He K, Kang J, Hong G, Zhu J, Li Y, Lin H, Xu H, Li Y (2019) Covariance-insured screening. Computational Statistics and Data Analysis: 132, 100—114.
3. He K, Xu H, Kang J† (2019) A selective overview of feature screening methods with applications to neuroimaging data, WRIES Computational Statistics, 11(2) e1454
4. Chen S, Xing Y, Kang J, Kochunov P, Hong LE (2018). Bayesian modeling of dependence in brain connectivity, Biostatistics, In Press.
5. Kang J, Reich BJ, Staicu AM (2018) Scalar-on-image regression via the soft thresholded Gaussian process. Biometrika: 105(1) 165–184.
6. Xue W, Bowman D and Kang J (2018) A Bayesian spatial model to predict disease status using imaging data from various modalities. Frontiers in Neuroscience. 12:184. doi:10.3389/fnins.2018.00184
7. Jin Z*, Kang J†, Yu T (2018) Missing value imputation for LC-MS metabolomics data by incorporating metabolic network and adduct ion relations. Bioinformatics, 34(9):1555—1561.
8. He K, Kang J† (2018) Comments on “Computationally efficient multivariate spatio-temporal models for high-dimensional count-valued data “. Bayesian Analysis, 13(1) 289-291.
9. Hong GH, Kang J†, Li Y (2018) Conditional screening for ultra-high dimensional covariates with survival outcomes. Lifetime Data Analysis: 24(1) 45-71.
10. Zhao Y*, Kang J†, Long Q (2018) Bayesian multiresolution variable selection for ultra-high dimensional neuroimaging data. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 15(2):537-550. (Earlier version won student paper award from ASA section on statistical learning and data mining in JSM 2014; It was also ranked as one of the top two papers in the student paper award competition in ASA section on statistics in imaging in JSM 2014)
11. Kang J, Hong GH, Li Y (2017) Partition-based ultrahigh dimensional variable screening, Biometrika, 104(4): 785-800.
12. Xie J#, Kang J# (2017) High dimensional tests for functional networks of brain anatomic regions. Journal of Multivariate Analysis, 156:70-88.
13. Cai Q*, Alvarez JA, Kang J†, Yu T (2017) Network marker selection for untargeted LC/MS metabolomics data, Journal of Proteome Research, 16(3):1261-1269
14. Kang J, Bowman FD, Mayberg H, Liu H (2016) A depression network of functionally connected regions discovered via multi-attribute canonical correlation graphs. NeuroImage, 41:431-441.

Walter Dempsey

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Dr. Dempsey’s research focuses on statistical methods for digital and mobile health. My current work involves three complementary research themes: (1) experimental design and data analytic methods to inform multi-stage decision making in health; (2) statistical modeling of complex longitudinal and survival data; and (3) statistical modeling of complex relational structures such as interaction networks. Current directions include (1) integration of sequential multiple assignment randomized trials (SMARTs) and micro-randomized trials (MRTs) and associated causal inference methods; (2) recurrent event analysis in the presence of high-frequency sensor data; and (3) temporal models for, community detection of, and link prediction using complex interaction data.

Veera Baladandayuthapani

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Dr. Veera Baladandayuthapani is currently a Professor in the Department of Biostatistics at University of Michigan (UM), where he is also the Associate Director of the Center for Cancer Biostatistics. He joined UM in Fall 2018 after spending 13 years in the Department of Biostatistics at University of Texas MD Anderson Cancer Center, Houston, Texas, where was a Professor and Institute Faculty Scholar and held adjunct appointments at Rice University, Texas A&M University and UT School of Public Health. His research interests are mainly in high-dimensional data modeling and Bayesian inference. This includes functional data analyses, Bayesian graphical models, Bayesian semi-/non-parametric models and Bayesian machine learning. These methods are motivated by large and complex datasets (a.k.a. Big Data) such as high-throughput genomics, epigenomics, transcriptomics and proteomics as well as high-resolution neuro- and cancer- imaging. His work has been published in top statistical/biostatistical/bioinformatics and biomedical/oncology journals. He has also co-authored a book on Bayesian analysis of gene expression data. He currently holds multiple PI-level grants from NIH and NSF to develop innovative and advanced biostatistical and bioinformatics methods for big datasets in oncology. He has also served as the Director of the Biostatistics and Bioinformatics Cores for the Specialized Programs of Research Excellence (SPOREs) in Multiple Myeloma and Lung Cancer and Biostatistics&Bioinformatics platform leader for the Myeloma and Melanoma Moonshot Programs at MD Anderson. He is a fellow of the American Statistical Association and an elected member of the International Statistical Institute. He currently serves as an Associate Editor for Journal of American Statistical Association, Biometrics and Sankhya.

 

An example of horizontal (across cancers) and vertical (across multiple molecular platforms) data integration. Image from Ha et al (Nature Scientific Reports, 2018; https://www.nature.com/articles/s41598-018-32682-x)

Mousumi Banerjee

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My research is primarily focused around 1) machine learning methods for understanding healthcare delivery and outcomes in the population, 2) analyses of correlated data (e.g. longitudinal and clustered data), and 3) survival analysis and competing risks analyses. We have developed tree-based and ensemble regression methods for censored and multilevel data, combination classifiers using different types of learning methods, and methodology to identify representative trees from an ensemble. These methods have been applied to important areas of biomedicine, specifically in patient prognostication, in developing clinical decision-making tools, and in identifying complex interactions between patient, provider, and health systems for understanding variations in healthcare utilization and delivery. My substantive areas of research are cancer and pediatric cardiovascular disease.

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.

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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.

Bhramar Mukherjee

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Bhramar Mukherjee is  a Professor in the Department of Biostatistics, joining the department in Fall, 2006. Bhramar is also a Professor in the Department of Epidemiology. Bhramar completed her Ph.D. in 2001 from Purdue University. Bhramar’s principal research interests lie in Bayesian methods in epidemiology and studies of gene-environment interaction. She is also interested in modeling missingness in exposure, categorical data models, Bayesian nonparametrics, and the general area of statistical inference under outcome/exposure dependent sampling schemes. Bhramar’s methodological research is funded by NSF and NIH.   Bhramar is involved as a co-investigator in several R01s led by faculty in Internal Medicine, Epidemiology and Environment Health sciences at UM. Her collaborative interests focus on genetic and environmental epidemiology, ranging from investigating the genetic architecture of colorectal cancer in relation to environmental exposures to studies of air pollution on pediatric Asthma events in Detroit. She is actively engaged in Global Health Research.

Sebastian Zoellner

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Sebastian Zöllner is a Professor of Biostatistics. He also holds an appointment in the Department of Psychiatry. Dr. Zöllner joined the University of Michigan after a postdoctoral fellowship in the Department of Human Genetics at the University of Chicago. His research effort is divided between generating new methods in statistical genetics and analyzing data. The general thrust of his work is problems from human genetics, evolutionary biology and statistical population biology.

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.

Trivellore E. Raghunathan

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Dr. Raghunathan’s primary research interest is in developing methods for dealing with missing data in sample surveys and in epidemiological studies. The methods are motivated from a Bayesian perspective but with desirable frequency or repeated sampling properties. The analysis of incomplete data from practical sample surveys poses additional problems due to extensive stratification, clustering of units and unequal probabilities of selection. The model-based approach provides a framework to incorporate all the relevant sampling design features in dealing with unit and item nonresponse in sample surveys. There are important computational challenges in implementing these methods in practical surveys. He has developed SAS based software, IVEware, for performing multiple imputation analysis and the analysis of complex survey data. Raghunathan’s other research interests include Bayesian methods, methods for small area estimation, combining information from multiple surveys, measurement error models, longitudinal data analysis, privacy, confidentiality and disclosure limitations and statistical methods for epidemiological studies. His applied interests include cardiovascular epidemiology, social epidemiology, health disparity, health care utilization, and social and economic sciences. Raghunathan is also involved in the Survey Methodology Program at the Institute for Social Research, a multidisciplinary team of sociologists, statisticians and psychologists, provides an opportunity to address methodological issues in: nonresponse, interviewer behavior and its impact on the results, response or measurement bias and errors, noncoverage, respondent cognition, privacy and confidentiality issues and data archiving. The Survey Methodology Program has a graduate program offering masters and doctoral degrees in survey methodology.