Molecular Distance Maps: An alignment-free computational tool for analyzing and visualizing DNA sequences\u27 interrelationships

In an attempt to identify and classify species based on genetic evidence, we propose a novel combination of methods to quantify and visualize the interrelationships between thousand of species. This is possible by using Chaos Game Representation (CGR) of DNA sequences to compute genomic signatures which we then compare by computing pairwise distances. In the last step, the original DNA sequences are embedded in a high dimensional space using Multi-Dimensional Scaling (MDS) before everything is projected on a Euclidean 3D space. To start with, we apply this method to a mitochondrial DNA dataset from NCBI containing over 3,000 species. The analysis shows that the oligomer composition of full mtDNA sequences can be a source of taxonomic information, suggesting that this method could be used for unclassified species and taxonomic controversies. Next, we test the hypothesis that CGR-based genomic signature is preserved along a species\u27 genome by comparing inter- and intra-genomic signatures of nuclear DNA sequences from six different organisms, one from each kingdom of life. We also compare six different distances and we assess their performance using statistical measures. Our results support the existence of a genomic signature for a species\u27 genome at the kingdom level. In addition, we test whether CGR-based genomic signatures originating only from nuclear DNA can be used to distinguish between closely-related species and we answer in the negative. To overcome this limitation, we propose the concept of ``composite signatures\u27\u27 which combine information from different types of DNA and we show that they can effectively distinguish all closely-related species under consideration. We also propose the concept of ``assembled signatures\u27\u27 which, among other advantages, do not require a long contiguous DNA sequence but can be built from smaller ones consisting of ~100-300 base pairs. Finally, we design an interactive webtool MoDMaps3D for building three-dimensional Molecular Distance Maps. The user can explore an already existing map or build his/her own using NCBI\u27s accession numbers as input. MoDMaps3D is platform independent, written in Javascript and can run in all major modern browsers

Biocomplexity and Fractality in the Search of Biomarkers of Aging and Pathology: Focus on Mitochondrial DNA and Alzheimer's Disease

Alzheimer's disease (AD) represents one major health concern for our growing elderly population. It accounts for increasing impairment of cognitive capacity followed by loss of executive function in late stage. AD pathogenesis is multifaceted and difficult to pinpoint, and understanding AD etiology will be critical to effectively diagnose and treat the disease. An interesting hypothesis concerning AD development postulates a cause-effect relationship between accumulation of mitochondrial DNA (mtDNA) mutations and neurodegenerative changes associated with this pathology. Here we propose a computerized method for an easy and fast mtDNA mutations-based characterization of AD. The method has been built taking into account the complexity of living being and fractal properties of many anatomic and physiologic structures, including mtDNA. Dealing with mtDNA mutations as gaps in the nucleotide sequence, fractal lacunarity appears a suitable tool to differentiate between aging and AD. Therefore, Chaos Game Representation method has been used to display DNA fractal properties after adapting the algorithm to visualize also heteroplasmic mutations. Parameter β from our fractal lacunarity method, based on hyperbola model function, has been measured to quantitatively characterize AD on the basis of mtDNA mutations. Results from this pilot study to develop the method show that fractal lacunarity parameter β of mtDNA is statistically different in AD patients when compared to age-matched controls. Fractal lacunarity analysis represents a useful tool to analyze mtDNA mutations. Lacunarity parameter β is able to characterize individual mutation profile of mitochondrial genome and appears a promising index to discriminate between AD and aging

Mitochondrial DNA Profiling by Fractal Lacunarity to Characterize the Senescent Phenotype as Normal Aging or Pathological Aging

Biocomplexity, chaos, and fractality can explain the heterogeneity of aging individuals by regarding longevity as a "secondary product" of the evolution of a dynamic nonlinear system. Genetic-environmental interactions drive the individual senescent phenotype toward normal, pathological, or successful aging. Mitochondrial dysfunctions and mitochondrial DNA (mtDNA) mutations represent a possible mechanism shared by disease(s) and the aging process. This study aims to characterize the senescent phenotype and discriminate between normal (nA) and pathological (pA) aging by mtDNA mutation profiling. MtDNA sequences from hospitalized and non-hospitalized subjects (age-range: 65-89 years) were analyzed and compared to the revised Cambridge Reference Sequence (rCRS). Fractal properties of mtDNA sequences were displayed by chaos game representation (CGR) method, previously modified to deal with heteroplasmy. Fractal lacunarity analysis was applied to characterize the senescent phenotype on the basis of mtDNA sequence mutations. Lacunarity parameter beta, from our hyperbola model function, was statistically different (p < 0.01) between the nA and pA groups. Parameter beta cut-off value at 1.26 x 10(-3) identifies 78% nA and 80% pA subjects. This also agrees with the presence of MT-CO gene variants, peculiar to nA (C9546m, 83%) and pA (T9900w, 80%) mtDNA, respectively. Fractal lacunarity can discriminate the senescent phenotype evolving as normal or pathological aging by individual mtDNA mutation profile

DNA Sequence Classification: It’s Easier Than You Think: An open-source k-mer based machine learning tool for fast and accurate classification of a variety of genomic datasets

Supervised classification of genomic sequences is a challenging, well-studied problem with a variety of important applications. We propose an open-source, supervised, alignment-free, highly general method for sequence classification that operates on k-mer proportions of DNA sequences. This method was implemented in a fully standalone general-purpose software package called Kameris, publicly available under a permissive open-source license. Compared to competing software, ours provides key advantages in terms of data security and privacy, transparency, and reproducibility. We perform a detailed study of its accuracy and performance on a wide variety of classification tasks, including virus subtyping, taxonomic classification, and human haplogroup assignment. We demonstrate the success of our method on whole mitochondrial, nuclear, plastid, plasmid, and viral genomes, as well as randomly sampled eukaryote genomes and transcriptomes. Further, we perform head-to-head evaluations on the tasks of HIV-1 virus subtyping and bacterial taxonomic classification with a number of competing state-of-the-art software solutions, and show that we match or exceed all other tested software in terms of accuracy and speed

Individual-Based Modeling and Nonlinear Analysis for Complex Systems with Application to Theoretical Ecology

One approach to understanding the behaviour of complex systems is individual-based modeling, which provides a bottom-up approach allowing for the consideration of the traits and behaviour of individual organisms. Ecosystem models aim to characterize the major dynamics of ecosystems, in order to synthesize the understanding of such systems and to allow predictions of their behaviour. Moreover, ecosystem simulations have the potential to help scientists address theoretical questions as well as helping with ecological resource management. Because in reality biologists do not have much data regarding variations in ecosystems over long periods of time, using the results of ecological computer simulation for making reasonable predictions can help biologists to better understand the long-term behaviour of ecosystems. Different versions of ecosystem simulations have been developed to investigate several questions in ecology such as how speciation proceeds in the absence of experimenter-defined functions. I have investigated some of these questions relying on complex interactions between the many individuals involved in the system, as well as long-term evolutionary patterns and processes such as speciation and macroevolution. Most scientists now believe that natural phenomena have to be looking as a chaotic system. In the past few years, chaos analysis techniques have gained increasing attention over a variety of applications. I have analyzed results of complex models to see whether chaotic behaviour can emerge, since any attempt to model a realistic system needs to have the capacity to generate patterns as complex as the ones that are observed in real systems. To further understand the complex behaviour of real systems, a new algorithm for long-term prediction of time series behaviour is also proposed based on chaos analysis. We evaluated the performance of our new method with respect to the prediction of the Dow-Jones industrial index time series, epileptic seizure and global temperature anomaly

2015 Oklahoma Research Day Full Program

This document contains all abstracts from the 2015 Oklahoma Research Day held at Northeastern State University