Computational Biology Commons^™

Computational Model For Survey And Trend Analysis Of Patients With Endometriosis : A Decision Aid Tool For Ebm, Salvo Reina, Vito Reina, Franco Ameglio, Mauro Costa, Alessandro Fasciani

COBRA Preprint Series

Endometriosis is increasingly collecting worldwide attention due to its medical complexity and social impact. The European community has identified this as a “social disease”. A large amount of information comes from scientists, yet several aspects of this pathology and staging criteria need to be clearly defined on a suitable number of individuals. In fact, available studies on endometriosis are not easily comparable due to a lack of standardized criteria to collect patients’ informations and scarce definitions of symptoms. Currently, only retrospective surgical stadiation is used to measure pathology intensity, while the Evidence Based Medicine (EBM) requires shareable methods and correct …

Pathoscope 2.0: A Complete Computational Framework For Strain Identification In Environmental Or Clinical Sequencing Samples., Changjin Hong, Solaiappan Manimaran, Ying Shen, Joseph F Perez-Rogers, Allyson L Byrd, Eduardo Castro-Nallar, Keith A Crandall, William Evan Johnson

Computational Biology Institute

BACKGROUND: Recent innovations in sequencing technologies have provided researchers with the ability to rapidly characterize the microbial content of an environmental or clinical sample with unprecedented resolution. These approaches are producing a wealth of information that is providing novel insights into the microbial ecology of the environment and human health. However, these sequencing-based approaches produce large and complex datasets that require efficient and sensitive computational analysis workflows. Many recent tools for analyzing metagenomic-sequencing data have emerged, however, these approaches often suffer from issues of specificity, efficiency, and typically do not include a complete metagenomic analysis framework.

RESULTS: We present PathoScope …

Characteristics And Prediction Of Rna Structure., Hengwu Li, Daming Zhu, Caiming Zhang, Huijian Han, Keith A Crandall

Computational Biology Institute

RNA secondary structures with pseudoknots are often predicted by minimizing free energy, which is NP-hard. Most RNAs fold during transcription from DNA into RNA through a hierarchical pathway wherein secondary structures form prior to tertiary structures. Real RNA secondary structures often have local instead of global optimization because of kinetic reasons. The performance of RNA structure prediction may be improved by considering dynamic and hierarchical folding mechanisms. This study is a novel report on RNA folding that accords with the golden mean characteristic based on the statistical analysis of the real RNA secondary structures of all 480 sequences from RNA …

Ether Bridge Formation And Chemical Diversification In Loline Alkaloid Biosynthesis, Juan Pan

Theses and Dissertations--Plant Pathology

Loline alkaloids, found in many grass-Epichloë symbiota, are toxic or feeding deterrent to invertebrates. The loline alkaloids all share a saturated pyrrolizidine ring with a 1-amine group and an ether bridge linking C2 and C7. The steps in biosynthesis of loline alkaloids are catalyzed by enzymes encoded by a gene cluster, designated LOL, in the Epichloë genome. This dissertation addresses the enzymatic, genetic and evolutionary basis for diversification of these alkaloids, focusing on ether bridge formation and the subsequent modifications of the 1-amine to form different loline alkaloids.

Through gene complementation of a natural lolO mutant and comparison …

Epistasis In Predator-Prey Relationships, Iuliia Inozemtseva

College of Graduate Studies: Theses & Dissertations

Epistasis is the interaction between two or more genes to control a single phenotype. We model epistasis of the prey in a two-locus two-allele problem in a basic predator- prey relationship. The resulting model allows us to examine both population sizes as well as genotypic and phenotypic frequencies. In the context of several numerical examples, we show that if epistasis results in an undesirable or desirable phenotype in the prey by making the particular genotype more or less susceptible to the predator or dangerous to the predator, elimination of undesirable phenotypes and then genotypes occurs.

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Semantics In Support Of Biodiversity Knowledge Discovery: An Introduction To The Biological Collections Ontology And Related Ontologies, Ramona L. Walls, John Deck, Robert Guralnick, Steve Baskauf, Reed Beaman, Stanley Blum, Shaun Bowers

Computer Science Faculty Scholarship

The study of biodiversity spans many disciplines and includes data pertaining to species distributions and abundances, genetic sequences, trait measurements, and ecological niches, complemented by information on collection and measurement protocols. A review of the current landscape of metadata standards and ontologies in biodiversity science suggests that existing standards such as the Darwin Core terminology are inadequate for describing biodiversity data in a semantically meaningful and computationally useful way. Existing ontologies, such as the Gene Ontology and others in the Open Biological and Biomedical Ontologies (OBO) Foundry library, provide a semantic structure but lack many of the necessary terms to …

Small Rna Expression During Programmed Rearragement Of A Vertebrate Genome, Joseph R. Herdy Iii

Theses and Dissertations--Biology

The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during embryogenesis that results in the deletion of ~0.5 Gb of germline DNA from the somatic lineage. The underlying mechanism of these rearrangements remains largely unknown. miRNAs (microRNAs) and piRNAs (PIWI interacting RNAs) are two classes of small noncoding RNAs that play important roles in early vertebrate development, including differentiation of cell lineages, modulation of signaling pathways, and clearing of maternal transcripts. Here, I utilized next generation sequencing to determine the temporal expression of miRNAs, piRNAs, and other small noncoding RNAs during the first five days of lamprey …

Identifying Potential Cancer Driver Genes By Genomic Data Integration., Yong Chen, Jingjing Hao, Wei Jiang, Tong He, Xuegong Zhang, Tao Jiang, Rui Jiang

College of Science & Mathematics Departmental Research

Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis …

On The Origin Of Phenotypic Variation: Novel Technologies To Dissect Molecular Determinants Of Phenotype, Francesco Vallania

All Theses and Dissertations (ETDs)

This thesis describes the conception, design, and development of novel computational tools, theoretical models, and experimental techniques applied to the dissection of molecular factors underlying phenotypic variation. The first part of my work is focused on finding rare genetic variants in pooled DNA samples, leading to the development of a novel set of algorithms, SNPseeker and SPLINTER, applied to next-generation sequencing data. The second part of my work describes the creation of a reporter system for DNA methylation for the purpose of dissecting the genetic contribution of tissue-specific patterns of DNA methylation across the genome. Finally the last part of …

Introducing A Novel Method For Genetic Analysis Of Autism Spectrum Disorder, Sepideh Nouri

Dissertations and Theses (Open Access)

Autism is a spectrum of neurological disorders that is characterized by repetitive and stereotyped behaviors, lack of social skills in verbal and non-verbal communications, and intellectual disability. Recent statistics shows that 1 out of every 88 children in the US is affected by autism.

In this thesis, I first review previous studies on genetic association analyses of autism spectrum disorder. A large number of these studies fall into two categories: Genome Wide Association Studies (GWAS) and sequencing studies. Although GWAS are able to identify multiple common risk variants associated with different diseases, these common variants explain only a small portion …

Homeotic Gene Teashirt (Tsh) Has A Neuroprotective Function In Amyloid-Beta 42 Mediated Neurodegeneration, Michael T. Moran, Meghana Tare, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Background: Alzheimer's disease (AD) is a debilitating age related progressive neurodegenerative disorder characterized by the loss of cognition, and eventual death of the affected individual. One of the major causes of AD is the accumulation of Amyloid-beta 42 (Aβ42) polypeptides formed by the improper cleavage of amyloid precursor protein (APP) in the brain. These plaques disrupt normal cellular processes through oxidative stress and aberrant signaling resulting in the loss of synaptic activity and death of the neurons. However, the detailed genetic mechanism(s) responsible for this neurodegeneration still remain elusive.

Methodology/Principal Findings: We have generated a transgenic Drosophila eye model where …

Pathoscope: Species Identification And Strain Attribution With Unassembled Sequencing Data., Owen E Francis, Matthew Bendall, Solaiappan Manimaran, Changjin Hong, Nathan L Clement, Eduardo Castro-Nallar, Quinn Snell, G Bruce Schaalje, Mark J Clement, Keith A Crandall, W Evan Johnson

Computational Biology Institute

Emerging next-generation sequencing technologies have revolutionized the collection of genomic data for applications in bioforensics, biosurveillance, and for use in clinical settings. However, to make the most of these new data, new methodology needs to be developed that can accommodate large volumes of genetic data in a computationally efficient manner. We present a statistical framework to analyze raw next-generation sequence reads from purified or mixed environmental or targeted infected tissue samples for rapid species identification and strain attribution against a robust database of known biological agents. Our method, Pathoscope, capitalizes on a Bayesian statistical framework that accommodates information on sequence …

Detecting Modules In Multiplex Networks – An Application For Integrating Expression Profiles Across Multiple Species, Koon-Kiu Yan, Daifeng Wang, Joel Rozowsky, Henry Zheng, Baikang Pei, Mark Gerstein

Yale Day of Data

Multiplex network, a set of networks linked through interconnected layers, is a useful mathematical framework for data integration. Here, we present a general method to detect modules in multiplex networks and apply it in a specific biological context: to simultaneously cluster the genome-wide expression profiles of C. elegans and D. melanogaster generated by the ENOCDE and modENCODE consortia. The method revealed modules that are fundamentally cross-species and can either be conserved or species-specific. In general, the method could be applied in various contexts like the integration of different social networks.

A Unified Framework Integrating Parent-Of-Origin Effects For Association Study, Feifei Xiao, Jianzhong Ma, Christopher I. I. Amos

Dartmouth Scholarship

Genetic imprinting is the most well-known cause for parent-of-origin effect (POE) whereby a gene is differentially expressed depending on the parental origin of the same alleles. Genetic imprinting is related to several human disorders, including diabetes, breast cancer, alcoholism, and obesity. This phenomenon has been shown to be important for normal embryonic development in mammals. Traditional association approaches ignore this important genetic phenomenon. In this study, we generalize the natural and orthogonal interactions (NOIA) framework to allow for estimation of both main allelic effects and POEs. We develop a statistical (Stat-POE) model that has the orthogonal estimates of parameters including …

Creating A Package In R, Brit Schneiders, Eric Archer

STAR Program Research Presentations

In a time of increasingly efficient technology and data production, scientists are producing data faster than it can be analyzed. Therefore, user accessibility to data analysis is becoming more and more critical. In general, researchers have a set of raw data and want an efficient means to their final analysis. A package serves as that means by creating a set of functions and making them accessible to the user. Often, a user has a small piece of code to run (a single R script, for example), and that script requires the use of certain functions, which are contained in a …

Physiologically-Based Pharmacokinetic Modeling For Predicting Caffeine/Theophylline-Ciprofloxacin Interactions, David M. Ng, Ali Navid

STAR Program Research Presentations

Dynamics of interactions between the drugs caffeine, theophylline, and ciprofloxacin are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drugs are distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body are reflected in the structure and functioning of the model. Multiple drugs can interact to increase or decrease their beneficial and/or undesired effects. This is important because some common substances, such as caffeine in coffee, soft drinks, and energy drinks, are actually drugs that affect the body. Ciprofloxacin is an inhibitor of caffeine and theophylline metabolism; such inhibition …

Rna-Sequencing Applications: Gene Expression Quantification And Methylator Phenotype Identification, Guoshuai Cai

Dissertations and Theses (Open Access)

My dissertation focuses on two aspects of RNA sequencing technology. The first is the methodology for modeling the overdispersion inherent in RNA-seq data for differential expression analysis. This aspect is addressed in three sections. The second aspect is the application of RNA-seq data to identify the CpG island methylator phenotype (CIMP) by integrating datasets of mRNA expression level and DNA methylation status.

Section 1: The cost of DNA sequencing has reduced dramatically in the past decade. Consequently, genomic research increasingly depends on sequencing technology. However it remains elusive how the sequencing capacity influences the accuracy of mRNA expression measurement. We …

Transcription Factor Binding Profiles Reveal Cyclic Expression Of Human Protein-Coding Genes And Non-Coding Rnas, Chao Cheng, Matthew Ung, Gavin D. Grant, Michael L. Whitfield

Dartmouth Scholarship

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and …

A Comprehensive And Integrative Reconstruction Of Evolutionary History For Anomura (Crustacea: Decapoda)., Heather D Bracken-Grissom, Maren E Cannon, Patricia Cabezas, Rodney M Feldmann, Carrie E Schweitzer, Shane T Ahyong, Darryl L Felder, Rafael Lemaitre, Keith A Crandall

Computational Biology Institute

BACKGROUND: The infraorder Anomura has long captivated the attention of evolutionary biologists due to its impressive morphological diversity and ecological adaptations. To date, 2500 extant species have been described but phylogenetic relationships at high taxonomic levels remain unresolved. Here, we reconstruct the evolutionary history-phylogeny, divergence times, character evolution and diversification-of this speciose clade. For this purpose, we sequenced two mitochondrial (16S and 12S) and three nuclear (H3, 18S and 28S) markers for 19 of the 20 extant families, using traditional Sanger and next-generation 454 sequencing methods. Molecular data were combined with 156 morphological characters in order to estimate the largest …