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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.

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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.

 

Mingyan Liu

Mingyan Liu

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Prof. Liu’s research interest lies in optimal resource allocation, sequential decision theory, online and machine learning, performance modeling, analysis, and design of large-scale, decentralized, stochastic and networked systems, using tools including stochastic control, optimization, game theory and mechanism design. Her most recent research activities involve sequential learning, modeling and mining of large scale Internet measurement data concerning cyber security, and incentive mechanisms for inter-dependent security games. Within this context, her research group is actively working on the following directions.

1. Cyber security incident forecast. The goal is to predict an organization’s likelihood of having a cyber security incident in the near future using a variety of externally collected Internet measurement data, some of which capture active maliciousness (e.g., spam and phishing/malware activities) while others capture more latent factors (e.g., misconfiguration and mismanagement). While machine learning techniques have been extensively used for detection in the cyber security literature, using them for prediction has rarely been done. This is the first study on the prediction of broad categories of security incidents on an organizational level. Our work to date shows that with the right choice of feature set, highly accurate predictions can be achieved with a forecasting window of 6-12 months. Given the increasing amount of high profile security incidents (Target, Home Depot, JP Morgan Chase, and Anthem, just to name a few) and the amount of social and economic cost they inflict, this work will have a major impact on cyber security risk management.

2. Detect propagation in temporal data and its application to identifying phishing activities. Phishing activities propagate from one network to another in a highly regular fashion, a phenomenon known as fast-flux, though how the destination networks are chosen by the malicious campaign remains unknown. An interesting challenge arises as to whether one can use community detection methods to automatically extract those networks involved in a single phishing campaign; the ability to do so would be critical to forensic analysis. While there have been many results on detecting communities defined as subsets of relatively strongly connected entities, the phishing activity exhibits a unique propagating property that is better captured using an epidemic model. By using a combination of epidemic modeling and regression we can identify this type of propagating community with reasonable accuracy; we are working on alternative methods as well.

3. Data-driven modeling of organizational and end-user security posture. We are working to build models that accurately capture the cyber security postures of end-users as well as organizations, using large quantities of Internet measurement data. One domain is on how software vendors disclose security vulnerabilities in their products, how they deploy software upgrades and patches, and in turn, how end users install these patches; all these elements combined lead to a better understanding of the overall state of vulnerability of a given machine and how that relates to user behaviors. Another domain concerns the interconnectedness of today’s Internet which implies that what we see from one network is inevitably related to others. We use this connection to gain better insight into the conditions of not just a single network viewed in isolation, but multiple networks viewed together.

A predictive analytics approach to forecasting cyber security incidents. We start from Internet-scale measurement on the security postures of network entities. We also collect security incident reports to use as labels in a supervised learning framework. The collected data then goes through extensive processing and domain-specific feature extraction. Features are then used to train a classifier that generates predictions when we input new features, on the likelihood of a future incident for the entity associated with the input features. We are also actively seeking to understand the causal relationship among different features and the security interdependence among different network entities. Lastly, risk prediction helps us design better incentive mechanisms which is another facet of our research in this domain.

A predictive analytics approach to forecasting cyber security incidents. We start from Internet-scale measurement on the security postures of network entities. We also collect security incident reports to use as labels in a supervised learning framework. The collected data then goes through extensive processing and domain-specific feature extraction. Features are then used to train a classifier that generates predictions when we input new features, on the likelihood of a future incident for the entity associated with the input features. We are also actively seeking to understand the causal relationship among different features and the security interdependence among different network entities. Lastly, risk prediction helps us design better incentive mechanisms which is another facet of our research in this domain.

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Jeffrey S. McCullough

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My research focuses on technology and innovation in health care with an emphasis on information technology (IT), pharmaceuticals, and empirical methods.  Many of my studies explored the effect of electronic health record (EHR) systems on health care quality and productivity. While the short-run gains from health IT adoption may be modest, these technologies form the foundation for a health information infrastructure. We are just beginning to understand how to harness and apply medical information. This problem is complicated by the sheer complexity of medical care, the heterogeneity across patients, and the importance of treatment selection. My current work draws on methods from both machine learning and econometrics to address these issues. Current pharmaceutical studies examine the roles of consumer heterogeneity and learning about the value of products as well as the effect of direct-to-consumer advertising on health.

The marginal effects of health IT on mortality by diagnosis and deciles of severity. We study the affect of hospitals' electronic health record (EHR) systems on patient outcomes. While we observe no benefits for the average patient, mortality falls significantly for high-risk patients in all EHR-sensitive conditions. These patterns, combined findings from other analyses, suggest that EHR systems may be more effective at supporting care coordination and information management than at rules-based clinical decision support. McCullough, Parente, and Town, "Health information technology and patient outcomes: the role of information and labor coordination." RAND Journal of Economics, Vol. 47, no. 1 (Spring 2016).

The marginal effects of health IT on mortality by diagnosis and deciles of severity. We study the affect of hospitals’ electronic health record (EHR) systems on patient outcomes. While we observe no benefits for the average patient, mortality falls significantly for high-risk patients in all EHR-sensitive conditions. These patterns, combined findings from other analyses, suggest that EHR systems may be more effective at supporting care coordination and information management than at rules-based clinical decision support. McCullough, Parente, and Town, “Health information technology and patient outcomes: the role of information and labor coordination.” RAND Journal of Economics, Vol. 47, no. 1 (Spring 2016).

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Charles Mayo

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My research interests are focused improving how we care for our patients by developing analytics tools that automate providing quantitative and statistical measures to augment qualitative and anecdotal evaluation. This requires technical efforts, to create databases and software, and clinical efforts, to integrate data aggregation, analysis and use into routine processes. Construction of knowledge based clinical practice improvement databases and standardizations in nomenclatures and ontologies needed to automate aggregation for all patients in a practice and enable data exchanges within and among institutions are facets of this work. A recent example includes, design implementation and use of an electronic prescription database to improve per patient treatment plan evaluation and enable longitudinal monitoring of results of practice quality improvement efforts.  We are also leading a group, sponsored by our professional societies, to define national standards for naming used in data exchanges for clinical trials. Another facet is improvement of patient treatment plan evaluation. Traditionally qualitative, visual inspection of spatial dose relationships to target and normal tissues is used to evaluate plans.  Development of algorithms to calculate vectorized dose volume histograms and other vector based spatial-dose objects provide a means to quantify those evaluations. Recently use of databases of dose information have enabled construction of statistical metrics to improve treatment plan evaluation and development of models for quantifying relationships to outcomes.

Data science applicationsdata driven clinical practice improvement, multi-institutional analysis of factors affecting patient outcomes and practice characterization, nomenclature and ontology.

Santiago Schnell

Santiago Schnell

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Dr. Schnell works at the interface between biophysical chemistry, mathematical and computational biology, and pathophysiology. As an independent scientist, his primary research interest is to use mathematical, computational and statistical methods to design or select optimal procedures and experiments, and to provide maximum information by analyzing biochemical data. His laboratory deals with the following topics:

(i) Development and implementation of mathematical, computational, and statistical methods to identify and characterize reaction mechanisms.

(ii) Investigate and test performance design of experiments or standards to quantify, interpret and analyze biochemical data.

(iii) Development of new algorithms and software to analyze biochemical data.

The key objective of my research is to create suitable standards and appropriate support of standards leading to reproducible results in the biochemical sciences. Reproducibility is central to scientific credibility. Meta-research has repeatedly shown that accurate reporting and sound peer-review do not by themselves guarantee the reproducibility of scientific results. One of the leading causes of poor reproducibility is limited research efforts in quantitative biology and chemometrics. In my laboratory, we are developing new ways to assess the reproducibility of quantitative findings in the biochemical sciences.

As a team scientist, Dr. Schnell’s research interest is to investigate complex biomedical systems comprising many interacting components, where modeling and theory may aid in the identification of the key mechanisms underlying the behavior of the system as a whole. His collaborators are primarily basic scientists who focus on the identification of molecular, biochemical or developmental mechanisms associated with diseases. To this end, Dr. Schnell’s expertise plays a central role in the identification of these mechanisms. Using mathematical and computational models, Dr. Schnell can formulate several hypothetical model mechanisms in parallel, which are compared with independent experimental data used to construct the models. The resulting comparisons are then independent between models, and any models that satisfy statistical measures of similarity will be used to make predictions, which will be tested experimentally by his collaborators. The model validated by the experiments will be considered the mechanism capable of explaining the behavior of the systems.

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Joseph Himle

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The goal of the research is to design, develop and test a inconspicuous, awareness-enhancement and monitoring device (AEMD) which will assist the treatment of trichotillomania (TTM), a disorder involving recurrent pulling of one’s hair resulting in noticeable hair loss. TTM is associated with significant impairments in social functioning and often has a profound negative impact on self-esteem and well being. Best practice treatment for TTM involves a form of behavioral therapy known as habit reversal therapy (HRT). HRT requires persons with trichotillomania to be aware of their hair pulling behaviors, yet the majority of persons with TTM pull most of their hair outside of their awareness . HRT also requires TTM sufferers to record the frequency and duration of their hair pulling behaviors yet it is obviously impossible for a person to monitor behaviors that they are unaware of. Our Phase I efforts have produced a prototype device (AEMD) that solves these two problems. The prototype AEMD signals the TTM sufferer if their hand approaches their hair, thereby bringing pulling-related behavior into awareness. The prototype AEMD also logs the time, date, duration, and user classification of hair pulling related events and can later transfer the logged data to a personal computer for analysis and data presentation. We continue to refine this device and seek to integrate it with smart-phones to better understand activities and locations associated with hair pulling or other body-focused repetitive behaviors (e.g., skin picking). In the future, we seek to pool data from users to get a better sense of common situations and other factors associated with elevated pulling rates. We intend to develop other electronic tools to detect, monitor and intervene with other mental disorders in the future.