Next Generation Cluster Editing

This work aims at improving the quality of structural variant prediction from the mapped reads of a sequenced genome. We suggest a new model based on cluster editing in weighted graphs and introduce a new heuristic algorithm that allows to solve this problem quickly and with a good approximation on the huge graphs that arise from biological datasets

Computational, Integrative, and Comparative Methods for the Elucidation of Genetic Coexpression Networks

Gene expression microarray data can be used for the assembly of genetic coexpression network graphs. Using mRNA samples obtained from recombinant inbred Mus musculus strains, it is possible to integrate allelic variation with molecular and higher-order phenotypes. The depth of quantitative genetic analysis of microarray data can be vastly enhanced utilizing this mouse resource in combination with powerful computational algorithms, platforms, and data repositories. The resulting network graphs transect many levels of biological scale. This approach is illustrated with the extraction of cliques of putatively coregulated genes and their annotation using gene ontology analysis and cis-regulatory element discovery. The causal basis for coregulation is detected through the use of quantitative trait locus mapping

Gene Regulatory Network Reconstruction Using Conditional Mutual Information

<p/> <p>The inference of gene regulatory network from expression data is an important area of research that provides insight to the inner workings of a biological system. The relevance-network-based approaches provide a simple and easily-scalable solution to the understanding of interaction between genes. Up until now, most works based on relevance network focus on the discovery of direct regulation using correlation coefficient or mutual information. However, some of the more complicated interactions such as interactive regulation and coregulation are not easily detected. In this work, we propose a relevance network model for gene regulatory network inference which employs both mutual information and conditional mutual information to determine the interactions between genes. For this purpose, we propose a conditional mutual information estimator based on adaptive partitioning which allows us to condition on both discrete and continuous random variables. We provide experimental results that demonstrate that the proposed regulatory network inference algorithm can provide better performance when the target network contains coregulated and interactively regulated genes.</p

Adaptive Double Self-Organizing Map for Clustering Gene Expression Data

This thesis presents a novel clustering technique known as adaptive double self- organizing map (ADSOM) that addresses the issue of identifying the correct number of clusters. ADSOM has a flexible topology and performs clustering and cluster visualization simultaneously, thereby requiring no a priori knowledge about the number of clusters. ADSOM combines features of the popular self-organizing map with two- dimensional position vectors, which serve as a visualization tool to decide the number of clusters. It updates its free parameters during training and it allows convergence of its position vectors to a fairly consistent number of clusters provided that its initial number of nodes is greater than the expected number of clusters. A novel index is introduced based on hierarchical clustering of the final locations of position vectors. The index allows automated detection of the number of clusters, thereby reducing human error that could be incurred from counting clusters visually. The reliance of ADSOM in identifying the number of clusters is proven by applying it to publicly available gene expression data from multiple biological systems such as yeast, human, mouse, and bacteria

Comparative Analysis of Thresholding Algorithms for Microarray-derived Gene Correlation Matrices

The thresholding problem is important in today’s data-rich research scenario. A threshold is a well-defined point in the data distribution beyond which the data is highly likely to have scientific meaning. The selection of threshold is crucial since it heavily influences any downstream analysis and inferences made there from. A legitimate threshold is one that is not arbitrary but scientifically well grounded, data-dependent and best segregates the information-rich and noisy sections of data. Although the thresholding problem is not restricted to any particular field of study, little research has been done. This study investigates the problem in context of network-based analysis of transcriptomic data. Six conceptually diverse algorithms – based on number of maximal cliques, correlations of control spots with genes, top 1% of correlations, spectral graph clustering, Bonferroni correction of p-values and statistical power – are used to threshold the gene correlation matrices of three time-series microarray datasets and tested for stability and validity. Stability or reliability of the first four algorithms towards thresholding is tested upon block bootstrapping of arrays in the datasets and comparing the estimated thresholds against the bootstrap threshold distributions. Validity of thresholding algorithms is tested by comparison of the estimated thresholds against threshold based on biological information. Thresholds based on the modular basis of gene networks are concluded to perform better both in terms of stability as well as validity. Future challenges to research the problem have been identified. Although the study utilizes transcriptomic data for analysis, we assert its applicability to thresholding across various fields

Report of the Regional Ecosystem Study Group of the North Sea (REGNS) [15-19 May 2006 ICES Headquarters, Copenhagen]

Contributors: Hein Rune Skjolda