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IMA Newsletter #421

November 2011

2011-2012 Program

See http://www.ima.umn.edu/2011-2012/ for a full description of the 2011-2012 program on Mathematics of Information.

IMA Events

Public Lecture

Cryptography: Secrets and Lies, Knowledge and Trust, Avi Wigderson (Institute for Advanced Study)

November 3, 2011

Speakers: Avi Wigderson (Institute for Advanced Study)

IMA Annual Program Year Workshop

Large Data Sets in Medical Informatics

November 14-18, 2011

Organizers: Nevenka Dimitrova (Philips Research Laboratory), W. Clem Karl (Boston University), Jean-Christophe Olivo-Marin (Institut Pasteur), Ahmed H. Tewfik (University of Texas)
Schedule

Tuesday, November 1

11:15am-12:15pm Regularization Methods for Probabilistic OptimizationGabriela Martínez (University of Minnesota)Keller Hall 3-180 PS
2:30pm-3:00pm Coffee breakLind Hall 400

Wednesday, November 2

2:30pm-3:00pm Coffee breakLind Hall 400

Thursday, November 3

2:30pm-3:00pm Coffee breakLind Hall 400
2:30pm-3:30pm The "P vs. NP" Problem: Efficient Computation, Internet Security, and the Limits to Human KnowledgeAvi Wigderson (Institute for Advanced Study)Lind Hall 305 S
7:00pm-8:00pm Cryptography: Secrets and Lies, Knowledge and TrustAvi Wigderson (Institute for Advanced Study)Willey Hall 175 PUB11.3.11

Friday, November 4

2:30pm-3:00pm Coffee breakLind Hall 400

Monday, November 7

2:30pm-3:00pm Coffee breakLind Hall 400

Tuesday, November 8

11:15am-12:15pm Exact semidefinite relaxation for the clustering and biclustering problemsBrendan P.W. Ames (University of Minnesota)Keller Hall 3-180 PS
2:30pm-3:00pm Coffee breakLind Hall 400

Wednesday, November 9

2:30pm-3:00pm Coffee breakLind Hall 400

Thursday, November 10

2:30pm-3:00pm Coffee breakLind Hall 400

Friday, November 11

2:30pm-3:00pm Coffee breakLind Hall 400

Monday, November 14

8:00am-8:45am Coffee and RegistrationKeller Hall 3-176 W11.14-18.11
8:45am-9:00am Welcome and IntroductionKeller Hall 3-180 W11.14-18.11
9:00am-10:00am Tutorial - Quantitative biological imaging: from cells to numbersJean-Christophe Olivo-Marin (Institut Pasteur)Keller Hall 3-180 W11.14-18.11
10:00am-10:15am Coffee BreakKeller Hall 3-176 W11.14-18.11
10:15am-11:15am Tutorial - Quantitative biological imaging: from cells to numbersJean-Christophe Olivo-Marin (Institut Pasteur)Keller Hall 3-180 W11.14-18.11
11:15am-11:30am Coffee BreakKeller Hall 3-176 W11.14-18.11
11:30am-12:30pm Scalable methods for analyzing 3D/4D/5D Images of Complex and Dynamic Biological MicroenvironmentsBadri Roysam (University of Houston)Keller Hall 3-180 W11.14-18.11
12:30pm-2:00pm Lunch W11.14-18.11
2:00pm-3:00pm How is Biology as a Science Possible?Edward R. Dougherty (Texas A & M University)Keller Hall 3-180 W11.14-18.11
3:00pm-3:15pm Coffee BreakKeller Hall 3-176 W11.14-18.11
3:15pm-4:15pm Pattern Discovery in Biomedical ModellingYi-Ping Phoebe Chen (La Trobe University)Keller Hall 3-180 W11.14-18.11
4:15pm-4:30pm Coffee BreakKeller Hall 3-176 W11.14-18.11
4:30pm-5:30pm Towards Closing the Semantic Gap in Decision Support for Clinical Sequencing in OncologyNevenka Dimitrova (Philips Research Laboratory)Keller Hall 3-180 W11.14-18.11
7:00pm-9:00pm Social Hour
Stub and Herbs
227 SE Oak St Minneapolis, MN 55455 Map
W11.14-18.11

Tuesday, November 15

8:30am-9:00am CoffeeKeller Hall 3-176 W11.14-18.11
9:00am-10:00am Tutorial - Translational medical imagingGuillermo R. Sapiro (University of Minnesota)Keller Hall 3-180 W11.14-18.11
10:00am-10:15am Coffee BreakKeller Hall 3-176 W11.14-18.11
10:15am-11:15am Tutorial - Translational medical imagingGuillermo R. Sapiro (University of Minnesota)Keller Hall 3-180 W11.14-18.11
11:15am-11:30am Coffee BreakKeller Hall 3-176 W11.14-18.11
11:30am-12:30pm Interactive Segmentation of 3D ImageryAllen Tannenbaum (Boston University)Keller Hall 3-180 W11.14-18.11
12:30pm-2:00pm Lunch W11.14-18.11
2:00pm-3:00pm Correlation-based variable selection for differential gene expression analysis Alfred O. Hero III (University of Michigan)Keller Hall 3-180 W11.14-18.11
3:00pm-3:15pm Coffee BreakKeller Hall 3-176 W11.14-18.11
3:15pm-4:15pm Impact of Sensing Structure in Classification of High-Dimensional Medical Informatics DataW. Clem Karl (Boston University)Keller Hall 3-180 W11.14-18.11
4:15pm-4:30pm Group Photo W11.14-18.11
4:30pm-6:30pm Reception and Poster SessionLind Hall 400 W11.14-18.11
Poster - Inverse Perturbation for Optimal Intervention in Genetic Regulatory NetworksNidhal Bouaynaya (University of Arkansas)
Dan Schonfeld (University of Illinois)
Poster - Exact Sample Conditioned Performance of Estimators for Classification Error Under Bayesian ContextsLori Dalton (Texas A & M University)
Poster - 3D Active Meshes: a versatile mathematical tool to study cell shape and motility in live microscopyAlexandre Dufour (Institut Pasteur)
Poster - Misaligned Principal Component AnalysisAlfred O. Hero III (University of Michigan)
Poster - Automatic Detection Of Vaccine Adverse Reactions By Incorporating Historical Medical ConditionsZhonghua Jiang (University of Minnesota)
George Karypis (University of Minnesota)

Wednesday, November 16

8:30am-9:00am CoffeeKeller Hall 3-176 W11.14-18.11
9:00am-10:00am Inverse problems in tomographic imagingCharles A. Bouman (Purdue University)Keller Hall 3-180 W11.14-18.11
10:00am-10:15am Coffee BreakKeller Hall 3-176 W11.14-18.11
10:15am-11:15am Inverse problems in tomographic imagingCharles A. Bouman (Purdue University)Keller Hall 3-180 W11.14-18.11
11:15am-11:30am Coffee BreakKeller Hall 3-176 W11.14-18.11
11:30am-12:30pm Designing fast and robust algorithms for medical image processingElsa Angelini (Telecom ParisTech)Keller Hall 3-180 W11.14-18.11
12:30pm-2:00pm Lunch W11.14-18.11
2:00pm-3:00pm Imaging development of the embryonic heart over multiple spatial dimensions, modalities and time-scalesMichael Liebling (University of California, Santa Barbara)Keller Hall 3-180 W11.14-18.11
3:00pm-3:15pm Coffee BreakKeller Hall 3-176 W11.14-18.11
3:15pm-4:15pm Multiscale Set Estimation in Biomedical Inverse ProblemsRebecca Willett (Duke University)Keller Hall 3-180 W11.14-18.11
4:15pm-4:30pm Coffee BreakKeller Hall 3-176 W11.14-18.11
4:30pm-5:30pm Large-Scale Multiple Testing in Medical InformaticsRobert Nowak (University of Wisconsin-Madison)Keller Hall 3-180 W11.14-18.11

Thursday, November 17

8:30am-9:00am CoffeeKeller Hall 3-176 W11.14-18.11
9:00am-10:00am Tutorial - Massive scale of DNA sequencing data presents challenges in processing and analysisFuli Yu (Baylor College of Medicine)Keller Hall 3-180 W11.14-18.11
10:00am-10:15am Coffee BreakKeller Hall 3-176 W11.14-18.11
10:15am-11:15am Tutorial - Massive scale of DNA sequencing data presents challenges in processing and analysisFuli Yu (Baylor College of Medicine)Keller Hall 3-180 W11.14-18.11
11:15am-11:30am Coffee BreakKeller Hall 3-176 W11.14-18.11
11:30am-12:30pm Large Data Challenges in Medical Imaging and BioinformaticsAhmed H. Tewfik (University of Texas at Austin)Keller Hall 3-180 W11.14-18.11
12:30pm-2:00pm Lunch W11.14-18.11
2:00pm-3:00pm Estimation of Individual’s Risk for Complex Trait Diseases: Methods and Challenges using Allelic Specific Expression and Mapping Cis-variance from NGS Data (RNA and Exome Sequencing Data)Shipra Agrawal (BioCOS Life Sciences Private Limited)Keller Hall 3-180 W11.14-18.11
3:00pm-3:15pm Coffee Break W11.14-18.11
3:15pm-4:15pm Intervention and Control of Large-Scale Gene Regulatory NetworksNidhal Bouaynaya (University of Arkansas)
Dan Schonfeld (University of Illinois)
Keller Hall 3-180 W11.14-18.11
4:15pm-5:00pm DiscussionKeller Hall 3-180 W11.14-18.11

Friday, November 18

8:30am-9:00am CoffeeKeller Hall 3-176 W11.14-18.11
9:00am-10:00am 3-D reconstructions of biological macromolecular complexes by electron microscopyPeter C Doerschuk (Cornell University)Keller Hall 3-180 W11.14-18.11
10:00am-10:15am Coffee BreakKeller Hall 3-176 W11.14-18.11
10:15am-11:15am Modeling and Acceleration of Maximum A Posteriori Reconstruction from Large CT DatasetsJean-Baptiste Thibault (GE Healthcare)Keller Hall 3-180 W11.14-18.11
11:15am-11:30am Coffee BreakKeller Hall 3-176 W11.14-18.11
11:30am-12:30pm Using Algorithms to Produce High Content Information from Cell and Tissue ImagesJens Rittscher (General Electric)Keller Hall 3-180 W11.14-18.11

Monday, November 21

2:30pm-3:00pm Coffee breakLind Hall 400

Tuesday, November 22

11:15am-12:15pm TBAXin Liu (University of Minnesota)Keller Hall 3-180 PS
2:30pm-3:00pm Coffee breakLind Hall 400

Wednesday, November 23

2:30pm-3:00pm Coffee breakLind Hall 400

Thursday, November 24

All Day Thanksgiving Day. The IMA is closed.

Friday, November 25

All Day Floating Holiday. The IMA is closed.

Monday, November 28

2:30pm-3:00pm Coffee breakLind Hall 400

Tuesday, November 29

11:15am-12:15pm A novel M-estimator for robust PCATeng Zhang (University of Minnesota)Keller Hall 3-180 PS
2:30pm-3:00pm Coffee breakLind Hall 400

Wednesday, November 30

2:30pm-3:00pm Coffee breakLind Hall 400
Abstracts
Shipra Agrawal (BioCOS Life Sciences Private Limited) Estimation of Individual’s Risk for Complex Trait Diseases: Methods and Challenges using Allelic Specific Expression and Mapping Cis-variance from NGS Data (RNA and Exome Sequencing Data)
Abstract: In current genetic and clinical research, identification of disease specific variations particularly from non-coding RNA and cis-elements is a major bottleneck. Massively parallel sequencing of exome and transcriptome is widely being used to effectively interrogate the key protein-coding and non-coding RNA regions. In such scenarios, the deep sequencing data of exome and transcriptome could be used for estimating levels of allele-specific expression in diseased vs. control samples (case-control cohorts) and hence the identification of disease specific signatures. This provides a functional basis to identify the differentially expressed alleles, mono-allelic expression, imprinting of alleles and allele regulated alternative splicing. All such data and approaches together make a stronger strategy to predict the disease susceptibility alleles and their functional role in disease mechanism. Our approaches at BioCOS Life Sciences using the Next Generation Sequencing (NGS) data analysis for the precise detection of allele’s differential expression becomes important in identifying causal/susceptibility genes by mapping their variance in both coding and non-coding DNA/RNA regions.

I will present our current research work on developing methods and data processing approaches, which can be applied in identification of the susceptibility alleles using the combined approaches from RNA-Seq and Exome-Seq data as well as directly predicting them from RNA-Seq data. The talk will also discuss the existing bottlenecks in the area and approaches to obtain high quality results with a focus on calling genotypes from RNA-Seq data.
Brendan P.W. Ames (University of Minnesota) Exact semidefinite relaxation for the clustering and biclustering problems
Abstract: Identifying clusters of similar objects in data plays a significant role in a wide range of applications such as information retrieval, pattern recognition, computational biology, and image processing. We consider as a model problem for clustering the average weight k-disjoint clique problem (WKDC), whose goal is to identify the collection of k disjoint cliques of a given weighted complete graph maximizing the sum of the average edge weights over the complete subgraphs induced by these cliques. We show that this problem can be formulated as a nonconvex quadratic maximization problem and subsequently relaxed to a semidefinite program using symmetric matrix lifting. Although the WKDC problem is NP-hard, we show that this relaxation is exact under certain assumptions on the input graph. That is, the optimal solution for the original hard combinatorial problem can be recovered directly from the solution of the relaxed problem for certain program inputs. In particular, the semidefinite relaxation is exact for input graphs corresponding to data consisting of k large, distinct clusters and a small number of outliers.

This approach also yields a semidefinite relaxation for the biclustering problem with similar recovery guarantees. Given a set of objects and a set of features exhibited by these objects, biclustering seeks to simultaneously group the objects and features according to their expression levels. We pose this problem as partitioning of a weighted complete bipartite graph such that the edge weight within the resulting bicliques is maximized. As in our analysis of the WKDC problem, we consider a nonconvex quadratic programming formulation for this problem, and relax to semidefinite programming using matrix lifting. As before, we show that the correct partition of the objects and features can be recovered from the optimal solution of the semidefinite relaxation, in the case that the input instance consists of several disjoint sets of objects exhibiting similar features.
Elsa Angelini (Telecom ParisTech) Designing fast and robust algorithms for medical image processing
Abstract: Quantification from medical images involves three levels of developments: - Modeling of the organs - Extraction of the visual features - Formulation of the quantification task Regarding organ modeling, geometric encoding of the shape is designed as a tradeoff between flexibility and robustness. Encoding of the variability within a population is a complex task that can have drawbacks when handling pathological cases. On the other hand, generic anatomical knowledge, especially regarding the context of the organ, can provide rich and more robust information, with spatial relations for example. Regarding the visual features, images are richer than they appear in terms of tissue signature, embedding multiscale information. The field of image processing has evolved slowly in the design of sophisticated organ-specific visual features, the majority of them remaining very basic. Future challenges remain open regarding the need to correlate multi-modal tissue signatures with physiological characteristics. Formulation of the quantification task such as segmentation, tracking or detection of longitudinal changes can be formulated either with a deterministic or stochastic formalism. Algorithms remain poorly robust to image quality, lack of image calibration, parameter tuning and presence of pathologies. Finer interactions between algorithmic tuning and image content and better calibration of image content is currently under investigation to address this lack of robustness and reproducibility.

These three components of the pipeline will be discussed, with illustrations on brain, cardiac liver and obstetric data. Emphasis will be paid to the constraints of being fast and robust, in the context of handling large data sets with great variability and pathologies.
Nidhal Bouaynaya (University of Arkansas), Dan Schonfeld (University of Illinois) Intervention and Control of Large-Scale Gene Regulatory Networks
Abstract: We formulate the optimal intervention problem in genetic regulatory networks as a minimal-perturbation of the network in order to force it to converge to a desired steady-state distribution of gene regulation. We cast optimal intervention in gene regulation as a convex optimization problem, thus providing a globally optimal solution which can be efficiently computed using standard techniques for convex optimization. The criteria adopted for optimality is chosen to minimize potential adverse effects as a consequence of the intervention strategy. We consider a perturbation that minimizes (i) the overall energy of change between the original and controlled networks and (ii) the time needed to reach the desired steady-state of gene regulation. Moreover, we show that there is an inherent tradeoff between minimizing the energy of the perturbation and the convergence rate to the desired distribution. We further show that the optimal inverse perturbation control is robust to estimation errors in the original network. The proposed control is applied to the Human melanoma gene regulatory network.
Nidhal Bouaynaya (University of Arkansas), Dan Schonfeld (University of Illinois) Poster - Inverse Perturbation for Optimal Intervention in Genetic Regulatory Networks
Abstract: We formulate the optimal intervention problem in genetic regulatory networks as a minimal-perturbation of the network in order to force it to converge to a desired steady-state distribution of gene regulation. We cast optimal intervention in gene regulation as a convex optimization problem, thus providing a globally optimal solution which can be efficiently computed using standard techniques for convex optimization. The criteria adopted for optimality is chosen to minimize potential adverse effects as a consequence of the intervention strategy. We consider a perturbation that minimizes (i) the overall energy of change between the original and controlled networks and (ii) the time needed to reach the desired steady-state of gene regulation. Moreover, we show that there is an inherent tradeoff between minimizing the energy of the perturbation and the convergence rate to the desired distribution. We further show that the optimal inverse perturbation control is robust to estimation errors in the original network. The proposed control is applied to the Human melanoma gene regulatory network.
Yi-Ping Phoebe Chen (La Trobe University) Pattern Discovery in Biomedical Modelling
Abstract: Solving modern biomedical problems, especially, those involving genome data, requires advanced computational and analytical methods. The huge quantities of data and escalating demands of modern biomedical research increasingly require the sophistication and power of computational techniques for their pattern discovery. Key techniques include relational data management, pattern recognition, data mining, modelling and visualization of biomedical data. In this talk, I will demonstrate recent methodologies and data structures for gathering high-quality approximations and modelling of genomic information, and will use these innovations as the basis for developing methods to cluster and visualize biomedical data in pattern discovery.
Lori Dalton (Texas A & M University) Poster - Exact Sample Conditioned Performance of Estimators for Classification Error Under Bayesian Contexts
Abstract: In recent years, biomedicine has been faced with difficult high-throughput small-sample classification problems, which are typically validated with re-sampling error estimation methods such as cross-validation. While heuristically designed error estimation techniques may be acceptable in problems where large amounts of data are available, the small-sample setting is different because asymptotic results are not meaningful and validation becomes a critical issue. A recently proposed classifier error estimator places the problem in a signal estimation framework in the presence of uncertainty, thereby permitting a rigorous optimal solution in a minimum-mean-square error (MMSE) sense. The uncertainty in this model is relative to the parameters of the feature-label distributions, resulting in a Bayesian approach to error estimation. The same Bayesian framework also produces the theoretical MSE for both Bayesian error estimators and arbitrary error estimators, where uncertainty is again relative to the unknown model parameters and conditioned on the observed sample. Thus, the Bayesian error estimator has a unique advantage over classical error estimators in that its mathematical framework naturally gives rise to a practical expected measure of performance given a fixed sample.
Nevenka Dimitrova (Philips Research Laboratory) Towards Closing the Semantic Gap in Decision Support for Clinical Sequencing in Oncology
Abstract: Within only a decade since the first draft of the human genome, we’ve witness astonishing pace of development of technologies for high throughput molecular profiling that probe various aspects of genome biology and its relationship to tumorigenesis and cancer treatment. There have been giant steps towards cataloging massive amounts of data and providing fairly good annotation information. However, computational methods that tried to tease out the relationship between the genotype and its functional readout - in normal and cancer states – revealed a semantic gap that is yet to be bridged. Narrowing this gap is essential in order to develop meaningful clinical decision support technologies.

In addition to imaging modalities which give the gross tissue level properties, crucial decisions in the context of oncology therapy selection require molecular level information that are increasingly captured by the emerging sequencing modalities. We undertook part in multiple studies aiming to understand the tumor heterogeneity and response to chemotherapy. Our efforts span several complementary modalities. In this talk I will provide several examples from our recent high throughput genomic studies:

1. DNA Sequencing: Assembly and downstream analysis of genomic data from normal individuals to understand and establish variation within normal individuals at the single nucleotide and structural level as well as the functional impact of these variations.

2. RNA Sequencing, CNV and DNA methylation: analysis in the context of chemo- and biological therapy response in breast and ovarian cancer.

3. Integration into a computational framework that combines genome-wide DNA methylation, gene expression and copy number variation data in a comprehensive fashion with the aim of finding mechanistic associations as well as signatures indicative of therapy resistance.

Our goal is to include these modalities in a Comprehensive Clinical Decision Support system where we need to integrate sequencing with imaging, pathology and other clinical data.
Peter C Doerschuk (Cornell University) 3-D reconstructions of biological macromolecular complexes by electron microscopy
Abstract: ingle-particle cryo electron microscopy provides images of biological macromolecular complexes with spatial sampling on the order of 1-2 Angstrom. Combining on the order of 100,000 such images can result in 3-D reconstructions of the electron scattering intensity of the complex with a spatial resolution as fine as 4-5 Angstrom. Due to damage in the imaging process, each complex is imaged only once and therefore having a homogeneous ensemble of complexes is important. Algorithms and results will be presented for the case where the complexes are not homogeneous and the reconstruction yields a statistical description of the electron scattering intensity rather than a single unique intensity. Related work on computed electron tomography, where the electron scattering intensity of individual complexes are determined but at lower resolution will also be presented.
Edward R. Dougherty (Texas A & M University) How is Biology as a Science Possible?
Abstract: A perusal of the contemporary biological literature involving high-throughput data sets reveals the generation of a vast amount of data and an enormous number of models (classifiers, clusters, networks) derived from this data via a plethora of algorithms. There tends to be four interrelated characteristics common to these publications: (1) no experimental deign, (2) data sets where the number of measured variables greatly exceeds the number of replications, (3) algorithms whose performance is unknown for the populations to which they are applied – and often known to work poorly when applied to a small number of replicates, and (4) models that are epistemologically meaningless because they have not been validated. Hence, we find ourselves in a position somewhat akin to that confronted by Immanuel Kant in the Eighteenth Century when he famously asked, “How is metaphysics as a science possible?” Certainly there was a lot of “metaphysical” talk in the air, but to what sureties had it led? To address the problem, Kant had to tackle the meaning of science and then appreciate what constraints had to be placed on metaphysical statements to make them “scientific.” Fortunately for us, we do not have to take on the monumental task of characterizing scientific knowledge, an endeavor that stretched from Galileo to Einstein. But we do have to consider what constraints must be placed on biological statements to make them meaningful, that is, so that they constitute biological scientific knowledge. Moreover, we need to address a critical methodological scientific issue addressed by Kant: What differentiates productive observation of Nature from “groping in the dark,” to use his phrase?
Alexandre Dufour (Institut Pasteur) Poster - 3D Active Meshes: a versatile mathematical tool to study cell shape and motility in live microscopy
Abstract: Dynamic processes such as cell motility and deformation are key components of numerous scenarios including cell division & differentiation, morphogenesis, immune response strategies, but also parasite invasion, cancer development & proliferation and host-pathogen interactions. Continuous advances in microscopy imaging techniques have allowed scientists to shed light on many of these processes over extended periods of time, yielding huge amounts of time-lapse imaging data in multiple colors and various experimental conditions. In such context, visual interpretation and manual analysis have proved to be limited by the lack of reproducibility, user bias and fatigue. Scientists thus progressively turn to automatic quantification methods able to process spatiotemporal data in a robust and systematic manner. In this work we present a novel framework for automatic cell segmentation and tracking based on the theory of deformable models, and show how such a versatile mathematical tools can be used to extract various information related to cellular motility, shape analysis and morpho-dynamic studies.
Alfred O. Hero III (University of Michigan) Correlation-based variable selection for differential gene expression analysis
Abstract: The problem of variable selection is useful for identifying the principal drivers of differential gene-response under one or more treatments, phenotypes, or conditions. Once identified, such drivers can be targeted as potential knockouts or enhancers in drug discovery or diagnostic testing. In high throughput data such as gene or protein expression the large number of variables has made it impractical to implement all but the simplest univariate methods for variable selection, e.g., detecting significant shifts in t-test or Wilcoxon test statistics. We propose an alternative approach based on detecting significant shifts in patterns of connectivity of genes in a correlation graph or concentration graph. Remarkably, it is precisely when the sample size is small that the approach is scalable, e.g., to whole genome analysis. Furthermore a statistical performance analysis establishes phase transition behaviors and tight approximations to false discovery rate that can be used for error control. We will illustrate the approach on several gene expression datasets.
Alfred O. Hero III (University of Michigan) Poster - Misaligned Principal Component Analysis
Abstract: Principal component analysis (PCA) is a widely applied method for extracting structure from samples of high dimensional biological data. Often there exist misalignments between different samples and this can cause severe problems in PCA if not properly taken into account. For example, subject-dependent temporal differences in gene expression response to a treatment will create relative time shifts in the samples that decohere the PCA analysis. The sensitivity of PCA to such misalignments is severe, leading to phase transitions that can be studied using the spectral the theory of high dimensional matrices. With this as motivation, we propose a new method of PCA, called misPCA, that explicitly accounts for the effects of misalignments in the samples. We illustrate misPCA on clustering longitudinal temporal gene expression data.

With Arnau Tibau-Puig, Ami Wiesel, and Raj Rao Nadakuditi
Zhonghua Jiang (University of Minnesota), George Karypis (University of Minnesota) Poster - Automatic Detection Of Vaccine Adverse Reactions By Incorporating Historical Medical Conditions
Abstract: This paper extends the problem of vaccine adverse reaction detection by incorporating historical medical conditions. We propose a novel measure called dual-lift for this task, and formulate this problem in the framework of constraint pattern mining. We present a pattern mining algorithm DLiftMiner which utilizes a novel approach to upper bound the dual-lift measure for reducing the search space. Experimental results on both synthetic and real world datasets show that our method is effective and promising.
W. Clem Karl (Boston University) Impact of Sensing Structure in Classification of High-Dimensional Medical Informatics Data
Abstract: There has been an explosion of non-invasive biomedical sensing modalities that have revolutionized our ability to probe the biomedical world. Often decisions have to be made on the basis of these increasingly high-dimensional observations. An example would be the determination of cancer or stroke from indirect tomographic projection measurements. The problem is frequently exacerbated by the lack of labeled training samples from which to learn class models. In many cases, however, there exists a latent low-dimensional sensing structure that can potentially be exploited for inferencing aims. This work investigates the impact of latent sensing structure on supervised classification performance when the data dimension scales to infinity faster than the number of samples. In contrast to some existing studies, here the classification difficulty is held fixed and finite as the data dimension scales. For a binary supervised classification problem with Gaussian likelihood functions, it is shown that the asymptotic error probability converges to that of pure guessing if the sensing structure is totally ignored, whereas it converges to the Bayes risk if the sensing structure is sufficiently regular and the classification method is "sensing aware". It is also shown, however, that without suitable regularity in the latent low-dimensional sensing structure, it is impossible to attain nontrivial asymptotic error probability. These findings are validated through various simulations. Additional numerical results for support vector machines and sensitivity to mismatch between true and assumed structure are also provided.
Michael Liebling (University of California, Santa Barbara) Imaging development of the embryonic heart over multiple spatial dimensions, modalities and time-scales
Abstract: Recent breakthroughs in optical microscopy have enabled in vivo imaging of the embryonic heart as it develops and gains function. Despite these advances, it remains difficult to simultaneously characterize heart morphology, heart function (the embryonic heart is beating before it is fully developed), and gene expression levels. We have developed computational tools to capture, process, and combine images acquired with different microscopy modalities, at different temporal and spatial scales, and over multiple samples, in an effort to build a multi-dimensional model of the beating and developing heart where morphology, function, and genetics can be simultaneously studied. Here, I will discuss image acquisition protocols and reconstruction strategies to overcome instrumentation and biological limitations that prevent simultaneous acquisition of these large, high-dimensional data sets. These tools will facilitate quantitative and systematic characterization of both morphology and function and study their relationship to genetic and epi-genetic factors that affect development in normal and diseased hearts.
Gabriela Martínez (University of Minnesota) Regularization Methods for Probabilistic Optimization
Abstract: We analyze nonlinear stochastic optimization problems with joint probabilistic constraints using the concept of a $p$-efficient point of a probability distribution. If the problem is described by convex functions, we develop two algorithms based on first order optimality conditions and a dual approach to the problem. The algorithms yield an optimal solution for problems involving $alpha$-concave probability distributions. For arbitrary distributions, the algorithms provide upper and lower bounds for the optimal value and nearly optimal solutions. When the problem is described by continuously differentiable non-convex functions, we describe the tangent and the normal cone to the level set of the underlying probability function. Furthermore, we formulate first order and second order conditions of optimality based on the notion of $p$-efficient points. For the case of discrete distribution functions, we developed an augmented Lagrangian method based on progressive inner approximation of the level set of the probability function by generation of $p$-efficient points. Numerical experience is provided.
Robert Nowak (University of Wisconsin-Madison) Large-Scale Multiple Testing in Medical Informatics
Abstract: In this talk I will discuss the novel experimental designs for large-scale multiple hypothesis testing problems. Testing to determine which genes are differentially expressed in a certain disease is a classic instance of multiple testing in medical informatics. Tremendous progress has been made in high-dimensional inference and testing problems by exploiting intrinsic low-dimensional structure. Sparsity is perhaps the simplest model for low-dimensional structure. It is based on the assumption that the signal of interest can be represented as a combination of a small number of elementary components. Sparse recovery is the problem of determining which components are needed in the representation based on measurements of the signal. For example, diseases are often characterized by a relatively small number of genes, which can be identified using high-throughput experimental techniques. This talk focuses on two issues related to this line of research.

1. Most theory and methods for sparse recovery are based on non-adaptive measurements. I will discuss the advantages of sequential measurement schemes that adaptively focus sensing using information gathered throughout the measurement process. In particular, I will show that sequential testing procedures can be significantly more powerful than non-sequential methods in the high-dimensional setting.

2. The standard sparse recovery problem involves inferring sparse linear functions. I will discuss generalizations of the standard problem to the recovery of sparse multilinear functions. Such functions are characterized by multiplicative interactions between the input variables, with sparsity meaning that relatively few of all conceivable interactions are present. This problem is motivated by the study of interactions between processes in complex networked systems (e.g., among genes and proteins in living cells). Our results extend the notion of compressed sensing from the linear sparsity model to nonlinear forms of sparsity encountered in complex systems. In contrast to linear sparsity models, in the multilinear case the pattern of sparsity can significantly affect sensing requirements.
Jean-Christophe Olivo-Marin (Institut Pasteur) Tutorial - Quantitative biological imaging: from cells to numbers
Abstract: The lecture will present biological imaging topics ranging from fundamentals in microscopy to specific methods and algorithms for the processing and quantification of 2- and 3-D+t images sequences in biological microscopy. We will demonstrate algorithms of PSF approximations for image deconvolution, image segmentation, multi-particle tracking and active contours models for cell shape and deformation analysis. We will illustrate the application of our methods in projects related to the study of the dynamics of genes in cell nuclei, the movement of parasites in cells and the detection and tracking of microbes in cells. One specific goal in biological imaging is indeed to automate the quantification of dynamics parameters or the characterization of phenotypic and morphological changes occurring as a consequence of cell/cell or pathogens/host cells interactions. The availability of this information and its thorough analysis is indeed of key importance to help deciphering underlying molecular mechanisms of e.g. infectious diseases.
Jens Rittscher (General Electric) Using Algorithms to Produce High Content Information from Cell and Tissue Images
Abstract: While the chemical structure of DNA is well understood, determining how genome-encoded components function in an integrated manner to perform cellular and organismal function is still an open challenge. The talk will motivate that imaging, more specifically the extraction of quantitative information, plays a critical role in this process. Such measurements will enable the automatic monitoring of cellular and intracellular events, and providing information about specific molecular mechanisms in individual cells.

By providing some specific examples it will be illustrated how specific computer vision algorithms enable the analysis of data sets and complex biological specimens that cannot be analyzed through manual inspection. The talk will highlight specific examples on how image analysis algorithms can be used to extract high content data. Specifically I will show how image segmentation methods are used to extract protein expression information in a novel sequential multiplexing process GE developed. In addition it will be discussed how statistical shape analysis methods can be applied to assess cellular morphology as well as the structure of entire organisms. Finally, it will be shown how the analysis of apparent motion can be used to monitor cardiomyocyte populations.

While imaging data potentially has much to add to models for systems biology, the usefulness of imaging information is dependent on the quantitative nature of the data and other aspects of its quality. Developing an awareness of the important long-term factors and challenge will help ensure acceptance of image analysis methods. Today image analysis methods are already used to study complex biological processes.
Badri Roysam (University of Houston) Scalable methods for analyzing 3D/4D/5D Images of Complex and Dynamic Biological Microenvironments
Abstract: Modern optical microscopy has grown into a multi-dimensional imaging tool. It is now possible to record dynamic processes in living specimens in their spatial context and temporal order, yielding information-rich 5-D images (3-D space, time, spectra).Of particular interest are complex and dynamic tissuemicroenvironments that play critical roles in health and disease, e.g., tumors, stem-cell niches, brain tissue surrounding neuroprosthetic devices, retinal tissue, cancer stem-cell niches, glands, and immune system tissues.

The task of analyzing these images exceeds human ability due to the sheer volume of the data (images routinely exceed 20GB in size), its structural complexity, and the dynamic behaviors of cells and organelles. First, there is a need for automated systems to assist the human analyst to map the tissue anatomy, quantify structural associations, identify critical events, map event locations and timing to the tissue anatomic context, identify and quantify spatial and temporal dependencies, produce meaningful summaries of multivariate measurement data, and compare perturbed and normal datasets for testing hypotheses, exploration, and systems modeling. Beyond automation, there is a need for ³computational sensing² of tissue patterns and cell behaviors that are too subtle for the human visual system to detect.

In this talk, I will describe large-scale application of image processing, active machine learning, multivariate clustering, and parallel computation methods that enable scalable analysis of multi-dimensional microscopy data. A particularly valuable application of these methods is to validate the large-scale automated analysis results. All of the software from this work is free and open source (www.farsight-toolkit,org).
Guillermo R. Sapiro (University of Minnesota) Tutorial - Translational medical imaging
Abstract: In this talk I will describe some of our efforts in the area of translational medical imaging, and illustrate how mathematics and formalism play a fundamental role. I will start with our work on brain imaging, where we have developed entire analysis pipelines, going from fixing basic mathematical errors in the classical formulas of high resolution diffusion imaging (HARDI), all the way to studying gender and kinship in brain connectivity networks and to helping neuro-surgeons in deep brain stimulation procedures. I will then present some of our work on the analysis of the structure of HIV and other viruses with data obtained from cryo-tomography, a critical step in vaccine development. Additional applications for helping surgeons in the operating room will be mentioned as well.
Allen Tannenbaum (Boston University) Interactive Segmentation of 3D Imagery
Abstract: In this talk, we will describe a new interactive procedure for segmenting 3D data sets using a mixture of ideas from control and image processing. More precisely, using a Lyapunov control design, a balance is established between the influence of a data-driven gradient flow and the human’s input over time. Automatic segmentation is thus smoothly coupled with interactivity. An application of the mathematical methods to orthopedic segmentation is shown, demonstrating the expected transient and steady state behavior of the implicit segmentation function and auxiliary observer.
Jean-Baptiste Thibault (GE Healthcare) Modeling and Acceleration of Maximum A Posteriori Reconstruction from Large CT Datasets
Abstract: Recent increases in detector coverage and trigger frequencies have opened up new clinical applications in modern Computed Tomography, but have also led to an explosion in the volume of CT raw datasets. This represents a particular challenge for accurate tomographic image reconstruction, particularly when using a model-based iterative framework based on Maximum A Posteriori estimation. Inclusion of detector physics, tube response, noise statistics, and image modeling involves certain complexity that drives up reconstruction time. However, recent results have started to demonstrate the significant potential of model-based iterative reconstruction for ultra-low-dose imaging aimed at improving patient safety, as well as high quality results in other targeted applications such as low contrast complex abdomen imaging and high-resolution medullar and cortical bone. This poses a particular challenge to come up with fast convergent algorithms that do not trade-off significant quality for speed, and are amenable to modern parallel computing hardware.

This talk will present the modeling framework for high quality model-based tomographic reconstruction and its advantages relative to alternative iterative approaches designed primarily with concern about reconstruction speed. In the proposed approach, speed and quality can be thought of as relatively orthogonal design elements, to the extent that convergence is reasonably achieved. First, the formulation of the optimization problem fully defines the target quality level as a function of the number and accuracy of the models designed to explicitly explain x-ray attenuation measurements based on realistic modeling of scanner behavior and non-idealities. Second, a globally convergent optimization algorithm chosen among a variety of potential alternatives is optimized to realize the performance targets for fast convergence, efficient implementation, and massive parallelization for practical applications. The development and continuous amelioration of such tools and models for tomographic reconstruction promise the establishment of a new platform for iterative reconstruction in modern CT that may someday replace standard analytical methods for routine high-quality low-dose imaging.
Rebecca Willett (Duke University) Multiscale Set Estimation in Biomedical Inverse Problems
Abstract: Sparse decomposition methods are effective tools in a myriad biomedical inverse problems. However, in many settings reconstruction is only an intermediate goal preceding additional quantitative analysis. For instance, we may wish to classify tissue types in microscope images or identify tumors or lesions based on computed tomography data. This talk describes how sparse image decomposition methods can be used in conjunction with multiscale set estimation methods to improve subsequent quantitative analyses on large medical datasets. For instance, sparse decomposition for tissue differentiation breaks down in images with boundaries, but multiscale set estimation can be used to accurately identify regions where sparse decomposition can be effectively applied. Similarly, sparse image reconstruction methods alone can spend significant computing resources on estimating features irrelevant to the quantitative goals, but by incorporating multiscale set estimation metrics into the objective function we can perform accurate quantitative analysis much more quickly. This talk will cover both the theoretical underpinnings of these methods and their application to challenging large-scale problems in microendoscopy and tomography.
Fuli Yu (Baylor College of Medicine) Tutorial - Massive scale of DNA sequencing data presents challenges in processing and analysis
Abstract: Recent advancements in DNA sequencing technologies have led to wide dissemination of instrumentation, resulting data and excitement. As a result of declining costs and increasing in throughput, there is a rapid growth trajectory in the amount of sequence data production. It is predicted that DNA sequence data will soon become one of the largest data types requiring powerful infrastructure development and deployment in both software and hardware in order to enable routine and robust handling and analysis.

This tutorial will guide participants through multiple topics regarding the next generation sequencing (NGS) data production and processing. Emphasis will be placed on both didactic presentation and group discussion in the following areas: (1) What is happening; (2) The excitement; (3) Best practice-lessons from the 1000 Genomes Project; (4) Remaining bottlenecks in data handling; and (5) A view toward the future.

The HGSC has been pioneering the deployment of multiple NGS platforms (Roche 454, Illumina, SOLiD, PacBio, Ion Torrent), and spearheaded personal genomics (Waston Genome, Lupski Genome, and Beery Family), population genomics (1000 Genomes), cohort disease mapping (ARIC Studies), and Cancer Studies (TCGA, familial cancer). A great deal of experience in processing and handling NGS data and variant calling have been accumulated, which form a solid foundation to meet future challenges.

My group has been a major part of the 1000 Genomes Project for variant calling, imputation and integration for both low-coverage (~4X/genome) and exome data. We developed integrative variant analysis pipelines-Atlas2 and SNPTools (http://www.hgsc.bcm.tmc.edu/cascade-tech-software-ti.hgsc), which achieved high quality SNP and INDEL datasets in the 1000 Genomes Phase I project. I will share this experience as one example.
Teng Zhang (University of Minnesota) A novel M-estimator for robust PCA
Abstract: We formulate a convex minimization to robustly recover a subspace from a contaminated data set, partially sampled around it, and propose a fast iterative algorithm to achieve the corresponding minimum. We establish exact recovery by this minimizer, quantify the effect of noise and regularization, explain how to take advantage of a known intrinsic dimension and establish linear convergence of the iterative algorithm. We compare our method with many other algorithms for Robust PCA on synthetic and real data sets and demonstrate state-of-the-art speed and accuracy.
Visitors in Residence
Osama Y Abuomar Mississippi State University 11/13/2011 - 11/19/2011
Shipra Agrawal BioCOS Life Sciences Private Limited 11/13/2011 - 11/20/2011
Brendan P.W. Ames University of Minnesota 8/31/2011 - 8/30/2012
Elsa Angelini Telecom ParisTech 11/14/2011 - 11/18/2011
James Ashe University of Minnesota 11/14/2011 - 11/18/2011
Bubacarr Bah University of Edinburgh 9/15/2011 - 12/15/2011
Arindam Banerjee University of Minnesota 9/1/2011 - 6/30/2012
Andrew John Beveridge Macalester College 9/1/2011 - 5/15/2012
Peter Beyerlein Technische Hochschule Wildau (FH) 11/13/2011 - 11/19/2011
Sergey G Bobkov University of Minnesota 9/1/2011 - 6/30/2012
Nidhal Bouaynaya University of Arkansas 11/13/2011 - 11/18/2011
Charles A. Bouman Purdue University 11/13/2011 - 11/18/2011
Luca Capogna University of Minnesota 8/15/2011 - 6/10/2012
Aycil Cesmelioglu University of Minnesota 9/30/2010 - 8/30/2012
Yi-Ping Phoebe Chen La Trobe University 11/14/2011 - 11/19/2011
Paolo Codenotti University of Minnesota 9/1/2011 - 8/30/2012
Jintao Cui University of Minnesota 8/31/2010 - 8/30/2012
Lori Dalton Texas A & M University 11/13/2011 - 11/18/2011
Isabel K. Darcy University of Iowa 9/1/2011 - 6/30/2012
Nevenka Dimitrova Philips Research Laboratory 11/14/2011 - 11/18/2011
Peter C Doerschuk Cornell University 11/13/2011 - 11/18/2011
Edward R. Dougherty Texas A & M University 11/13/2011 - 11/16/2011
Alexandre Dufour Institut Pasteur 11/13/2011 - 11/18/2011
Dainius Dzindzalieta Vilnius State University 9/1/2011 - 12/31/2011
Leonardo Espin NONE 9/1/2011 - 6/30/2012
Arie Feuer Technion-Israel Institute of Technology 11/13/2011 - 11/18/2011
Qiang Fu University of Minnesota 11/14/2011 - 11/18/2011
Zoltan Furedi Hungarian Academy of Sciences (MTA) 9/22/2011 - 11/21/2011
Carlos Andres Garavito-Garzon University of Minnesota 9/8/2011 - 6/30/2012
Wuming Gong University of Minnesota 11/14/2011 - 11/18/2011
Marshall Hampton University of Minnesota 11/13/2011 - 11/15/2011
Alfred O. Hero III University of Michigan 11/13/2011 - 11/16/2011
Yulia Hristova University of Minnesota 9/1/2010 - 8/31/2012
Xiaoping Philip Hu Emory University 11/14/2011 - 11/16/2011
Zhonghua Jiang University of Minnesota 11/14/2011 - 11/18/2011
Chiu-Yen Kao Ohio State University 11/14/2011 - 11/17/2011
W. Clem Karl Boston University 11/13/2011 - 11/18/2011
George Karypis University of Minnesota 11/14/2011 - 11/18/2011
Rui Kuang University of Minnesota 11/14/2011 - 11/18/2011
Gilad Lerman University of Minnesota 9/1/2011 - 6/30/2012
Wenbo Li University of Delaware 9/1/2011 - 5/30/2012
Michael Liebling University of California, Santa Barbara 11/13/2011 - 11/17/2011
Xin Liu University of Minnesota 8/31/2011 - 8/30/2012
Shiqian Ma University of Minnesota 8/31/2011 - 8/30/2013
Rakesh Malladi Rice University 11/13/2011 - 11/19/2011
Yi Mao University of Washington 11/13/2011 - 11/18/2011
Yu (David) Mao University of Minnesota 8/31/2010 - 8/30/2012
Gabriela Martínez University of Minnesota 8/31/2011 - 8/30/2013
Saurabh Mishra Eagan High School 8/22/2011 - 12/31/2011
Dimitrios Mitsotakis University of Minnesota 10/27/2010 - 8/31/2012
Prateek Mittal University of Illinois at Urbana-Champaign 11/13/2011 - 11/19/2011
Chad Myers University of Minnesota 11/14/2011 - 11/18/2011
Linda A. Ness Telcordia 11/10/2011 - 11/14/2011
Robert Nowak University of Wisconsin-Madison 11/16/2011 - 11/17/2011
Jean-Christophe Olivo-Marin Institut Pasteur 11/13/2011 - 11/19/2011
Luke Olson University of Illinois at Urbana-Champaign 9/1/2011 - 12/31/2011
Broderick O. Oluyede Georgia Southern University 11/13/2011 - 11/18/2011
Mary Therese Padberg University of Iowa 8/16/2011 - 6/1/2012
Candice Renee Price University of Iowa 8/1/2011 - 7/31/2012
Weifeng (Frederick) Qiu University of Minnesota 8/31/2010 - 8/30/2012
Jens Rittscher General Electric 11/13/2011 - 11/18/2011
Badri Roysam University of Houston 11/13/2011 - 11/17/2011
Guillermo R. Sapiro University of Minnesota 9/1/2011 - 5/31/2012
Dan Schonfeld University of Illinois 11/13/2011 - 11/18/2011
Arthur Szlam University of Minnesota 8/31/2011 - 8/30/2012
Allen Tannenbaum Boston University 11/13/2011 - 11/18/2011
Jared Tanner University of Edinburgh 9/20/2011 - 12/15/2011
Ahmed H. Tewfik University of Texas at Austin 11/13/2011 - 11/19/2011
Jean-Baptiste Thibault GE Healthcare 11/13/2011 - 11/18/2011
Kursad Tosun Southern Illinois University 11/13/2011 - 11/18/2011
Divyanshu Vats University of Minnesota 8/31/2011 - 8/30/2012
Lan Wang University of Minnesota 9/1/2011 - 5/12/2012
Rachel Ward University of Texas at Austin 11/13/2011 - 11/26/2011
Rachel Ward University of Texas at Austin 10/23/2011 - 11/5/2011
Ke Wei University of Edinburgh 10/10/2011 - 12/10/2011
Elisabeth Werner Case Western Reserve University 9/1/2011 - 12/20/2011
Avi Wigderson Institute for Advanced Study 11/2/2011 - 11/4/2011
Rebecca Willett Duke University 11/15/2011 - 11/17/2011
Steve Wright University of Wisconsin-Madison 11/27/2011 - 12/3/2011
Lingzhou Xue University of Minnesota 9/1/2011 - 6/30/2012
Byung-Jun Yoon Texas A & M University 11/13/2011 - 11/18/2011
Fuli Yu Baylor College of Medicine 11/15/2011 - 11/18/2011
Ofer Zeitouni University of Minnesota 9/1/2011 - 12/9/2011
Teng Zhang University of Minnesota 8/31/2011 - 8/30/2012
Legend: Postdoc or Industrial Postdoc Long-term Visitor

IMA Affiliates:
Arizona State University, Boeing, Colorado State University, Corning Incorporated, ExxonMobil, Ford, General Motors, Georgia Institute of Technology, Honeywell, IBM, Indiana University, Iowa State University, Korea Advanced Institute of Science and Technology (KAIST), Lawrence Livermore National Laboratory, Lockheed Martin, Los Alamos National Laboratory, Medtronic, Michigan State University, Michigan Technological University, Mississippi State University, Northern Illinois University, Ohio State University, Pennsylvania State University, Portland State University, Purdue University, Rice University, Rutgers University, Sandia National Laboratories, Schlumberger Cambridge Research, Schlumberger-Doll, Seoul National University, Siemens, Telcordia, Texas A & M University, University of Central Florida, University of Chicago, University of Delaware, University of Houston, University of Illinois at Urbana-Champaign, University of Iowa, University of Kentucky, University of Maryland, University of Michigan, University of Minnesota, University of Notre Dame, University of Pennsylvania, University of Pittsburgh, University of Tennessee, University of Wisconsin-Madison, University of Wyoming, US Air Force Research Laboratory, Wayne State University, Worcester Polytechnic Institute