Coping with new Challenges in Clustering and Biomedical Imaging

The last years have seen a tremendous increase of data acquisition in different scientific fields such as molecular biology, bioinformatics or biomedicine. Therefore, novel methods are needed for automatic data processing and analysis of this large amount of data. Data mining is the process of applying methods like clustering or classification to large databases in order to uncover hidden patterns. Clustering is the task of partitioning points of a data set into distinct groups in order to minimize the intra cluster similarity and to maximize the inter cluster similarity. In contrast to unsupervised learning like clustering, the classification problem is known as supervised learning that aims at the prediction of group membership of data objects on the basis of rules learned from a training set where the group membership is known. Specialized methods have been proposed for hierarchical and partitioning clustering. However, these methods suffer from several drawbacks. In the first part of this work, new clustering methods are proposed that cope with problems from conventional clustering algorithms. ITCH (Information-Theoretic Cluster Hierarchies) is a hierarchical clustering method that is based on a hierarchical variant of the Minimum Description Length (MDL) principle which finds hierarchies of clusters without requiring input parameters. As ITCH may converge only to a local optimum we propose GACH (Genetic Algorithm for Finding Cluster Hierarchies) that combines the benefits from genetic algorithms with information-theory. In this way the search space is explored more effectively. Furthermore, we propose INTEGRATE a novel clustering method for data with mixed numerical and categorical attributes. Supported by the MDL principle our method integrates the information provided by heterogeneous numerical and categorical attributes and thus naturally balances the influence of both sources of information. A competitive evaluation illustrates that INTEGRATE is more effective than existing clustering methods for mixed type data. Besides clustering methods for single data objects we provide a solution for clustering different data sets that are represented by their skylines. The skyline operator is a well-established database primitive for finding database objects which minimize two or more attributes with an unknown weighting between these attributes. In this thesis, we define a similarity measure, called SkyDist, for comparing skylines of different data sets that can directly be integrated into different data mining tasks such as clustering or classification. The experiments show that SkyDist in combination with different clustering algorithms can give useful insights into many applications. In the second part, we focus on the analysis of high resolution magnetic resonance images (MRI) that are clinically relevant and may allow for an early detection and diagnosis of several diseases. In particular, we propose a framework for the classification of Alzheimer's disease in MR images combining the data mining steps of feature selection, clustering and classification. As a result, a set of highly selective features discriminating patients with Alzheimer and healthy people has been identified. However, the analysis of the high dimensional MR images is extremely time-consuming. Therefore we developed JGrid, a scalable distributed computing solution designed to allow for a large scale analysis of MRI and thus an optimized prediction of diagnosis. In another study we apply efficient algorithms for motif discovery to task-fMRI scans in order to identify patterns in the brain that are characteristic for patients with somatoform pain disorder. We find groups of brain compartments that occur frequently within the brain networks and discriminate well among healthy and diseased people

A survey of statistical network models

Networks are ubiquitous in science and have become a focal point for discussion in everyday life. Formal statistical models for the analysis of network data have emerged as a major topic of interest in diverse areas of study, and most of these involve a form of graphical representation. Probability models on graphs date back to 1959. Along with empirical studies in social psychology and sociology from the 1960s, these early works generated an active network community and a substantial literature in the 1970s. This effort moved into the statistical literature in the late 1970s and 1980s, and the past decade has seen a burgeoning network literature in statistical physics and computer science. The growth of the World Wide Web and the emergence of online networking communities such as Facebook, MySpace, and LinkedIn, and a host of more specialized professional network communities has intensified interest in the study of networks and network data. Our goal in this review is to provide the reader with an entry point to this burgeoning literature. We begin with an overview of the historical development of statistical network modeling and then we introduce a number of examples that have been studied in the network literature. Our subsequent discussion focuses on a number of prominent static and dynamic network models and their interconnections. We emphasize formal model descriptions, and pay special attention to the interpretation of parameters and their estimation. We end with a description of some open problems and challenges for machine learning and statistics.Comment: 96 pages, 14 figures, 333 reference

You can't always sketch what you want: Understanding Sensemaking in Visual Query Systems

Visual query systems (VQSs) empower users to interactively search for line charts with desired visual patterns, typically specified using intuitive sketch-based interfaces. Despite decades of past work on VQSs, these efforts have not translated to adoption in practice, possibly because VQSs are largely evaluated in unrealistic lab-based settings. To remedy this gap in adoption, we collaborated with experts from three diverse domains---astronomy, genetics, and material science---via a year-long user-centered design process to develop a VQS that supports their workflow and analytical needs, and evaluate how VQSs can be used in practice. Our study results reveal that ad-hoc sketch-only querying is not as commonly used as prior work suggests, since analysts are often unable to precisely express their patterns of interest. In addition, we characterize three essential sensemaking processes supported by our enhanced VQS. We discover that participants employ all three processes, but in different proportions, depending on the analytical needs in each domain. Our findings suggest that all three sensemaking processes must be integrated in order to make future VQSs useful for a wide range of analytical inquiries.Comment: Accepted for presentation at IEEE VAST 2019, to be held October 20-25 in Vancouver, Canada. Paper will also be published in a special issue of IEEE Transactions on Visualization and Computer Graphics (TVCG) IEEE VIS (InfoVis/VAST/SciVis) 2019 ACM 2012 CCS - Human-centered computing, Visualization, Visualization design and evaluation method

BClass: A Bayesian Approach Based on Mixture Models for Clustering and Classification of Heterogeneous Biological Data

Based on mixture models, we present a Bayesian method (called BClass) to classify biological entities (e.g. genes) when variables of quite heterogeneous nature are analyzed. Various statistical distributions are used to model the continuous/categorical data commonly produced by genetic experiments and large-scale genomic projects. We calculate the posterior probability of each entry to belong to each element (group) in the mixture. In this way, an original set of heterogeneous variables is transformed into a set of purely homogeneous characteristics represented by the probabilities of each entry to belong to the groups. The number of groups in the analysis is controlled dynamically by rendering the groups as 'alive' and 'dormant' depending upon the number of entities classified within them. Using standard Metropolis-Hastings and Gibbs sampling algorithms, we constructed a sampler to approximate posterior moments and grouping probabilities. Since this method does not require the definition of similarity measures, it is especially suitable for data mining and knowledge discovery in biological databases. We applied BClass to classify genes in RegulonDB, a database specialized in information about the transcriptional regulation of gene expression in the bacterium Escherichia coli. The classification obtained is consistent with current knowledge and allowed prediction of missing values for a number of genes. BClass is object-oriented and fully programmed in Lisp-Stat. The output grouping probabilities are analyzed and interpreted using graphical (dynamically linked plots) and query-based approaches. We discuss the advantages of using Lisp-Stat as a programming language as well as the problems we faced when the data volume increased exponentially due to the ever-growing number of genomic projects.

The Role of Clustered Organization and Generation of Mixed Properties in Macaque V2

Throughout the mammalian cortex, neurons of similar response characteristics group together into topographic functional domains. The genesis and role of this organization remains in question, but it has been proposed to affect the mixed properties of neurons. These types of neurons possess multiple receptive field preferences, such as a cell responding to a color and an oriented stimulus. To examine the functionality of clustered organization and their effect in generation of neurons possessing mixed properties, this dissertation examined the secondary visual cortex (V2) of the Macaca fasicularis. This particular cortex is comprised of domains organized according to distinct visual stimulus components, specifically clusters of neurons partitioned by color and orientation preferences within a close proximity. In the first series of experiments (Chapter 3), a computer model of a cortical area based upon macaque V2 investigated the effect of clusters of like-preferring neurons on the probability of two different preference terminals synapsing on a particular cell. These results indicate that presence of at least one cluster significantly increases the probability of multiple preferences arriving at a neuron. The second series of experiments (Chapter 4) used single unit electrophysiology to investigate the temporal properties of V2 neurons in response to achromatic and colored oriented stimuli. With the addition of color to the stimulus, an increase in latency, an increase to the time point of the maximum rate of firing, and a decreased initial-phase response with a sustained later-phase response were observed. These studies indicate that functional clusters of neurons significantly increase the joint probability of the co-localization of differing preference terminals, potentially yielding neurons with mixed preferences through these intra-areal connections. Furthermore, the temporal characteristics of V2 neurons, as seen in observed latency and time of maximum spiking, support this idea of domain-enhanced intra-areal integration

Efficient Knowledge Extraction from Structured Data

Knowledge extraction from structured data aims for identifying valid, novel, potentially useful, and ultimately understandable patterns in the data. The core step of this process is the application of a data mining algorithm in order to produce an enumeration of particular patterns and relationships in large databases. Clustering is one of the major data mining tasks and aims at grouping the data objects into meaningful classes (clusters) such that the similarity of objects within clusters is maximized, and the similarity of objects from different clusters is minimized. In this thesis, we advance the state-of-the-art data mining algorithms for analyzing structured data types. We describe the development of innovative solutions for hierarchical data mining. The EM-based hierarchical clustering method ITCH (Information-Theoretic Cluster Hierarchies) is designed to propose solid solutions for four different challenges. (1) to guide the hierarchical clustering algorithm to identify only meaningful and valid clusters. (2) to represent each cluster content in the hierarchy by an intuitive description with e.g. a probability density function. (3) to consistently handle outliers. (4) to avoid difficult parameter settings. ITCH is built on a hierarchical variant of the information-theoretic principle of Minimum Description Length (MDL). Interpreting the hierarchical cluster structure as a statistical model of the dataset, it can be used for effective data compression by Huffman coding. Thus, the achievable compression rate induces a natural objective function for clustering, which automatically satisfies all four above mentioned goals. The genetic-based hierarchical clustering algorithm GACH (Genetic Algorithm for finding Cluster Hierarchies) overcomes the problem of getting stuck in a local optimum by a beneficial combination of genetic algorithms, information theory and model-based clustering. Besides hierarchical data mining, we also made contributions to more complex data structures, namely objects that consist of mixed type attributes and skyline objects. The algorithm INTEGRATE performs integrative mining of heterogeneous data, which is one of the major challenges in the next decade, by a unified view on numerical and categorical information in clustering. Once more, supported by the MDL principle, INTEGRATE guarantees the usability on real world data. For skyline objects we developed SkyDist, a similarity measure for comparing different skyline objects, which is therefore a first step towards performing data mining on this kind of data structure. Applied in a recommender system, for example SkyDist can be used for pointing the user to alternative car types, exhibiting a similar price/mileage behavior like in his original query. For mining graph-structured data, we developed different approaches that have the ability to detect patterns in static as well as in dynamic networks. We confirmed the practical feasibility of our novel approaches on large real-world case studies ranging from medical brain data to biological yeast networks. In the second part of this thesis, we focused on boosting the knowledge extraction process. We achieved this objective by an intelligent adoption of Graphics Processing Units (GPUs). The GPUs have evolved from simple devices for the display signal preparation into powerful coprocessors that do not only support typical computer graphics tasks but can also be used for general numeric and symbolic computations. As major advantage, GPUs provide extreme parallelism combined with a high bandwidth in memory transfer at low cost. In this thesis, we propose algorithms for computationally expensive data mining tasks like similarity search and different clustering paradigms which are designed for the highly parallel environment of a GPU, called CUDA-DClust and CUDA-k-means. We define a multi-dimensional index structure which is particularly suited to support similarity queries under the restricted programming model of a GPU. We demonstrate the superiority of our algorithms running on GPU over their conventional counterparts on CPU in terms of efficiency