On functional module detection in metabolic networks

Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models

Doctor of Philosophy

dissertationWith the tremendous growth of data produced in the recent years, it is impossible to identify patterns or test hypotheses without reducing data size. Data mining is an area of science that extracts useful information from the data by discovering patterns and structures present in the data. In this dissertation, we will largely focus on clustering which is often the first step in any exploratory data mining task, where items that are similar to each other are grouped together, making downstream data analysis robust. Different clustering techniques have different strengths, and the resulting groupings provide different perspectives on the data. Due to the unsupervised nature i.e., the lack of domain experts who can label the data, validation of results is very difficult. While there are measures that compute "goodness" scores for clustering solutions as a whole, there are few methods that validate the assignment of individual data items to their clusters. To address these challenges we focus on developing a framework that can generate, compare, combine, and evaluate different solutions to make more robust and significant statements about the data. In the first part of this dissertation, we present fast and efficient techniques to generate and combine different clustering solutions. We build on some recent ideas on efficient representations of clusters of partitions to develop a well founded metric that is spatially aware to compare clusterings. With the ability to compare clusterings, we describe a heuristic to combine different solutions to produce a single high quality clustering. We also introduce a Markov chain Monte Carlo approach to sample different clusterings from the entire landscape to provide the users with a variety of choices. In the second part of this dissertation, we build certificates for individual data items and study their influence on effective data reduction. We present a geometric approach by defining regions of influence for data items and clusters and use this to develop adaptive sampling techniques to speedup machine learning algorithms. This dissertation is therefore a systematic approach to study the landscape of clusterings in an attempt to provide a better understanding of the data

Ensemble clustering via heuristic optimisation

This thesis was submitted for the degree of Doctor of Philosophy and was awarded by Brunel UniversityTraditional clustering algorithms have different criteria and biases, and there is no single algorithm that can be the best solution for a wide range of data sets. This problem often presents a significant obstacle to analysts in revealing meaningful information buried among the huge amount of data. Ensemble Clustering has been proposed as a way to avoid the biases and improve the accuracy of clustering. The difficulty in developing Ensemble Clustering methods is to combine external information (provided by input clusterings) with internal information (i.e. characteristics of given data) effectively to improve the accuracy of clustering. The work presented in this thesis focuses on enhancing the clustering accuracy of Ensemble Clustering by employing heuristic optimisation techniques to achieve a robust combination of relevant information during the consensus clustering stage. Two novel heuristic optimisation-based Ensemble Clustering methods, Multi-Optimisation Consensus Clustering (MOCC) and K-Ants Consensus Clustering (KACC), are developed and introduced in this thesis. These methods utilise two heuristic optimisation algorithms (Simulated Annealing and Ant Colony Optimisation) for their Ensemble Clustering frameworks, and have been proved to outperform other methods in the area. The extensive experimental results, together with a detailed analysis, will be presented in this thesis

VLSI Design

This book provides some recent advances in design nanometer VLSI chips. The selected topics try to present some open problems and challenges with important topics ranging from design tools, new post-silicon devices, GPU-based parallel computing, emerging 3D integration, and antenna design. The book consists of two parts, with chapters such as: VLSI design for multi-sensor smart systems on a chip, Three-dimensional integrated circuits design for thousand-core processors, Parallel symbolic analysis of large analog circuits on GPU platforms, Algorithms for CAD tools VLSI design, A multilevel memetic algorithm for large SAT-encoded problems, etc

Clustering in Hypergraphs to Minimize Average Edge Service Time

We study the problem of clustering the vertices of a weighted hypergraph such that on average the vertices of each edge can be covered by a small number of clusters. This problem has many applications such as for designing medical tests, clustering files on disk servers, and placing network services on servers. The edges of the hypergraph model groups of items that are likely to be needed together, and the optimization criteria which we use can be interpreted as the average delay (or cost) to serve the items of a typical edge. We describe and analyze algorithms for this problem for the case in which the clusters have to be disjoint and for the case where clusters can overlap. The analysis is often subtle and reveals interesting structure and invariants that one can utilize

The Data Big Bang and the Expanding Digital Universe: High-Dimensional, Complex and Massive Data Sets in an Inflationary Epoch

Recent and forthcoming advances in instrumentation, and giant new surveys, are creating astronomical data sets that are not amenable to the methods of analysis familiar to astronomers. Traditional methods are often inadequate not merely because of the size in bytes of the data sets, but also because of the complexity of modern data sets. Mathematical limitations of familiar algorithms and techniques in dealing with such data sets create a critical need for new paradigms for the representation, analysis and scientific visualization (as opposed to illustrative visualization) of heterogeneous, multiresolution data across application domains. Some of the problems presented by the new data sets have been addressed by other disciplines such as applied mathematics, statistics and machine learning and have been utilized by other sciences such as space-based geosciences. Unfortunately, valuable results pertaining to these problems are mostly to be found only in publications outside of astronomy. Here we offer brief overviews of a number of concepts, techniques and developments, some "old" and some new. These are generally unknown to most of the astronomical community, but are vital to the analysis and visualization of complex datasets and images. In order for astronomers to take advantage of the richness and complexity of the new era of data, and to be able to identify, adopt, and apply new solutions, the astronomical community needs a certain degree of awareness and understanding of the new concepts. One of the goals of this paper is to help bridge the gap between applied mathematics, artificial intelligence and computer science on the one side and astronomy on the other.Comment: 24 pages, 8 Figures, 1 Table. Accepted for publication: "Advances in Astronomy, special issue "Robotic Astronomy