DNA Microarray Data Analysis: A New Survey on Biclustering

There are subsets of genes that have similar behavior under subsets of conditions, so we say that they coexpress, but behave independently under other subsets of conditions. Discovering such coexpressions can be helpful to uncover genomic knowledge such as gene networks or gene interactions. That is why, it is of utmost importance to make a simultaneous clustering of genes and conditions to identify clusters of genes that are coexpressed under clusters of conditions. This type of clustering is called biclustering.Biclustering is an NP-hard problem. Consequently, heuristic algorithms are typically used to approximate this problem by finding suboptimal solutions. In this paper, we make a new survey on biclustering of gene expression data, also called microarray data

High-Throughput Polygenic Biomarker Discovery Using Condition-Specific Gene Coexpression Networks

Biomarkers can be described as molecular signatures that are associated with a trait or disease. RNA expression data facilitates discovery of biomarkers underlying complex phenotypes because it can capture dynamic biochemical processes that are regulated in tissue-specific and time-specific manners. Gene Coexpression Network (GCN) analysis is a method that utilizes RNA expression data to identify binary gene relationships across experimental conditions. Using a novel GCN construction algorithm, Knowledge Independent Network Construction (KINC), I provide evidence for novel polygenic biomarkers in both plant and animal use cases. Kidney cancer is comprised of several distinct subtypes that demonstrate unique histological and molecular signatures. Using KINC, I have identified gene correlations that are specific to clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer. ccRCC is associated with two common mutation profiles that respond differently to targeted therapy. By identifying GCN edges that are specific to patients with each of these two mutation profiles, I discovered unique genes with similar biological function, suggesting a role for T cell exhaustion in the development of ccRCC. Medicago truncatula is a legume that is capable of atmospheric nitrogen fixation through a symbiotic relationship between plant and rhizobium that results in root nodulation. This process is governed by complex gene expression patterns that are dynamically regulated across tissues over the course of rhizobial infection. Using de novo RNA sequencing data generated from the root maturation zone at five distinct time points, I identified hundreds of genes that were differentially expressed between control and inoculated plants at specific time points. To discover genes that were co-regulated during this experiment, I constructed a GCN using the KINC software. By combining GCN clustering analysis with differentially expressed genes, I present evidence for novel root nodulation biomarkers. These biomarkers suggest that temporal regulation of pathogen response related genes is an important process in nodulation. Large-scale GCN analysis requires computational resources and stable data-processing pipelines. Supercomputers such as Clemson University’s Palmetto Cluster provide data storage and processing resources that enable terabyte-scale experiments. However, with the wealth of public sequencing data available for mining, petabyte-scale experiments are required to provide novel insights across the tree of life. I discuss computational challenges that I have discovered with large scale RNA expression data mining, and present two workflows, OSG-GEM and OSG-KINC, that enable researchers to access geographically distributed computing resources to handle petabyte-scale experiments

Ant Colony Optimization

Ant Colony Optimization (ACO) is the best example of how studies aimed at understanding and modeling the behavior of ants and other social insects can provide inspiration for the development of computational algorithms for the solution of difficult mathematical problems. Introduced by Marco Dorigo in his PhD thesis (1992) and initially applied to the travelling salesman problem, the ACO field has experienced a tremendous growth, standing today as an important nature-inspired stochastic metaheuristic for hard optimization problems. This book presents state-of-the-art ACO methods and is divided into two parts: (I) Techniques, which includes parallel implementations, and (II) Applications, where recent contributions of ACO to diverse fields, such as traffic congestion and control, structural optimization, manufacturing, and genomics are presented

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Algorithmic Techniques in Gene Expression Processing. From Imputation to Visualization

The amount of biological data has grown exponentially in recent decades. Modern biotechnologies, such as microarrays and next-generation sequencing, are capable to produce massive amounts of biomedical data in a single experiment. As the amount of the data is rapidly growing there is an urgent need for reliable computational methods for analyzing and visualizing it. This thesis addresses this need by studying how to efficiently and reliably analyze and visualize high-dimensional data, especially that obtained from gene expression microarray experiments. First, we will study the ways to improve the quality of microarray data by replacing (imputing) the missing data entries with the estimated values for these entries. Missing value imputation is a method which is commonly used to make the original incomplete data complete, thus making it easier to be analyzed with statistical and computational methods. Our novel approach was to use curated external biological information as a guide for the missing value imputation. Secondly, we studied the effect of missing value imputation on the downstream data analysis methods like clustering. We compared multiple recent imputation algorithms against 8 publicly available microarray data sets. It was observed that the missing value imputation indeed is a rational way to improve the quality of biological data. The research revealed differences between the clustering results obtained with different imputation methods. On most data sets, the simple and fast k-NN imputation was good enough, but there were also needs for more advanced imputation methods, such as Bayesian Principal Component Algorithm (BPCA). Finally, we studied the visualization of biological network data. Biological interaction networks are examples of the outcome of multiple biological experiments such as using the gene microarray techniques. Such networks are typically very large and highly connected, thus there is a need for fast algorithms for producing visually pleasant layouts. A computationally efficient way to produce layouts of large biological interaction networks was developed. The algorithm uses multilevel optimization within the regular force directed graph layout algorithm.Siirretty Doriast

Fundamentals

Volume 1 establishes the foundations of this new field. It goes through all the steps from data collection, their summary and clustering, to different aspects of resource-aware learning, i.e., hardware, memory, energy, and communication awareness. Machine learning methods are inspected with respect to resource requirements and how to enhance scalability on diverse computing architectures ranging from embedded systems to large computing clusters

Evolutionary Genomics

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward