Computational Biology Commons^™

Efficient Reduced Bias Genetic Algorithm For Generic Community Detection Objectives, Aditya Karnam Gururaj Rao

Theses

The problem of community structure identification has been an extensively investigated area for biology, physics, social sciences, and computer science in recent years for studying the properties of networks representing complex relationships. Most traditional methods, such as K-means and hierarchical clustering, are based on the assumption that communities have spherical configurations. Lately, Genetic Algorithms (GA) are being utilized for efficient community detection without imposing sphericity. GAs are machine learning methods which mimic natural selection and scale with the complexity of the network. However, traditional GA approaches employ a representation method that dramatically increases the solution space to be searched by …

Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando

Computational Biology Institute

It has recently been hypothesized that stress exposure (e.g. via glucocorticoid secretion) may dysregulate the bacterial gut microbiome, a crucial 'organ' in animal health. However, whether stress exposure (e.g. via glucocorticoid secretion) affects the bacterial gut microbiome of natural populations is unknown. We have experimentally altered the basal glucocorticoid level (corticosterone implants) in a wild avian species, the yellow-legged gull

Prediction Of Lncrna-Disease Associations Based On Inductive Matrix Completion, Chengqian Lu, Mengyun Yang, Feng Luo, Fang-Xiang Wu, Min Li, Yi Pan, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA–disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA–disease associations, especially for novel lncRNAs, remains challenging.

Results: In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA– disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA–disease interactions and functional similarity of diseases based on disease–gene and gene–gene onotology …

Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson

Honors Program: Senior Projects (Public)

Copy number variations (CNVs) are large insertions, deletions, and duplications in the genome that vary between individuals in a species. These variations are known to impact a broad range of phenotypes from molecular-level traits to higher-order clinical phenotypes. CNVs have been linked to complex traits in humans such as autism, attention deficit hyperactivity disorder, nervous system disorders, and early-onset extreme obesity. In this study, whole-genome sequence was obtained from 72 founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska. This included 24 boars (12 Duroc and 12 Landrace) and …

Gene-Based Association Study For Lipid Traits In Diverse Cohorts Implicates Bace1 And Sidt2 Regulation In Triglyceride Levels, Angela Andaleon, Lauren S. Mogil, Heather Wheeler

Bioinformatics Faculty Publications

Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS) of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in CETP associated with HDL cholesterol (P = 9.0 × 10⁻¹⁰) and …

Benchmark Evaluation Of True Single Molecular Sequencing To Determine Cystic Fibrosis Airway Microbiome Diversity, Andrea Hahn, Matthew L. Bendall, Keylie M. Gibson, Hollis Chaney, Iman Sami, Geovanny F. Perez, Anastassios C. Koumbourlis, Timothy A. Mccaffrey, Robert J. Freishtat, Keith A Crandall

Computational Biology Institute

Cystic fibrosis (CF) is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS) and PathoScope in the analysis of the CF airway microbiome. Three control samples were created with differing amounts of Burkholderia cepacia, Pseudomonas aeruginosa, and Prevotella melaninogenica, three common bacteria found in cystic …

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted to …

Recurrent Neural Networks And Their Applications To Rna Secondary Structure Inference, Devin Willmott

Theses and Dissertations--Mathematics

Recurrent neural networks (RNNs) are state of the art sequential machine learning tools, but have difficulty learning sequences with long-range dependencies due to the exponential growth or decay of gradients backpropagated through the RNN. Some methods overcome this problem by modifying the standard RNN architecure to force the recurrent weight matrix W to remain orthogonal throughout training. The first half of this thesis presents a novel orthogonal RNN architecture that enforces orthogonality of W by parametrizing with a skew-symmetric matrix via the Cayley transform. We present rules for backpropagation through the Cayley transform, show how to deal with the Cayley …

Novel Computational Methods For Sequencing Data Analysis: Mapping, Query, And Classification, Xinan Liu

Theses and Dissertations--Computer Science

Over the past decade, the evolution of next-generation sequencing technology has considerably advanced the genomics research. As a consequence, fast and accurate computational methods are needed for analyzing the large data in different applications. The research presented in this dissertation focuses on three areas: RNA-seq read mapping, large-scale data query, and metagenomics sequence classification.

A critical step of RNA-seq data analysis is to map the RNA-seq reads onto a reference genome. This dissertation presents a novel splice alignment tool, MapSplice3. It achieves high read alignment and base mapping yields and is able to detect splice junctions, gene fusions, and circular …

A Systematic Approach To Rna-Associated Motif Discovery, Tian Gao, Jiang Shu, Juan Cui

School of Computing: Faculty Publications

Background: Sequencing-based large screening of RNA-protein and RNA-RNA interactions has enabled the mechanistic study of post-transcriptional RNA processing and sorting, including exosome-mediated RNA secretion. The downstream analysis of RNA binding sites has encouraged the investigation of novel sequence motifs, which resulted in exceptional new challenges for identifying motifs from very short sequences (e.g., small non-coding RNAs or truncated messenger RNAs), where conventional methods tend to be ineffective. To address these challenges, we propose a novel motif-finding method and validate it on a wide range of RNA applications.

Results: We first perform motif analysis on microRNAs and longer RNA fragments from …

Bacterial Inoculants, Endophytic Bacteria And Their Influence On Nicotiana Physiology, Development And Microbiome, Andrea Marisa Sanchez Barrios

Theses and Dissertations--Plant and Soil Sciences

Soil and root microbial communities have been studied for decades, and the incorporation of high-throughput techniques and analysis has allowed the identification of endophytic/non-culturable organisms. This has helped characterize and establish the core microbiome of many model plant species which include underground and aboveground organs. Unfortunately, the information obtained from some of these model plants is not always transferable to other agronomic species. In this project, we decided to study the microbiome of the Nicotiana genus because of its importance in plant physiological and plant-microbe interactions studies. The data obtained was used as baseline information that allowed us to better …

Estimating The Heritability Of Thermal Tolerance In Acropora Cervicornis And The Physiological Basis Of Adaptation That Correlates To Survival At Elevated Temperatures, Kelsey L. Yetsko

UNF Graduate Theses and Dissertations

Human activities have substantially increased the atmospheric concentrations of greenhouse gases, resulting in warmer ocean temperatures that are having a negative impact on reef corals, which are highly susceptible to changes in temperature. Understanding the degree to which species vary in their tolerance to elevated temperatures and whether this variation is heritable is important in determining their ability to adapt to climate change. In order to address this, Acropora cervicornis fragments from 20 genetically distinct colonies were kept at either ambient or elevated temperatures, and mortality was monitored for 26 days. Heritability of thermal tolerance was estimated using a clonal …

An Investigation Of Atomic Structures Derived From X-Ray Crystallography And Cryo-Electron Microscopy Using Distal Blocks Of Side-Chains, Lin Chen, Jing He, Salim Sazzed, Rayshawn Walker

Computer Science Faculty Publications

Cryo-electron microscopy (cryo-EM) is a structure determination method for large molecular complexes. As more and more atomic structures are determined using this technique, it is becoming possible to perform statistical characterization of side-chain conformations. Two data sets were involved to characterize block lengths for each of the 18 types of amino acids. One set contains 9131 structures resolved using X-ray crystallography from density maps with better than or equal to 1.5 Å resolutions, and the other contains 237 protein structures derived from cryo-EM density maps with 2-4 Å resolutions. The results show that the normalized probability density function of block …

Unseen Science: Modern Discoveries Too Far Away Or Tiny For Human Eyes, Lucy Huang

Capstones

As science has progressed, scientists have realized that evidence goes beyond the realms of physical sight. Whether it is too small or difficult to find, scientists have developed different ways to get around this problem. We see this in cancer genomics and in extrasolar planetary research. Scientists use what they know and what they measure to validate their work.

https://lucy-huang-9tge.squarespace.com/

Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande

KGI Theses and Dissertations

Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …

The Ability Of Different Imputation Methods To Preserve The Significant Genes And Pathways In Cancer, Rosa Aghdam, Taban Baghfalaki, Pegah Khosravi, Elnaz Saberi Ansari

Publications and Research

Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM) method was applied to detect the significant genes in rectal and lung cancers to showcase …

Bayesian Prediction Intervals For Assessing P-Value Variability In Prospective Replication Studies, Olga A. Vsevolozhskaya, Gabriel Ruiz, Dmitri Zaykin

Biostatistics Faculty Publications

Increased availability of data and accessibility of computational tools in recent years have created an unprecedented upsurge of scientific studies driven by statistical analysis. Limitations inherent to statistics impose constraints on the reliability of conclusions drawn from data, so misuse of statistical methods is a growing concern. Hypothesis and significance testing, and the accompanying P-values are being scrutinized as representing the most widely applied and abused practices. One line of critique is that P-values are inherently unfit to fulfill their ostensible role as measures of credibility for scientific hypotheses. It has also been suggested that while P-values …

In Silico Study Of Newly Synthesized Opioid Analgesics Bound To Three Opioid Receptors, Abdullah Allaoa, Mai Zahran

Publications and Research

Opioids are the most widely used drugs for the treatment of moderate to severe, chronic pain. They achieve antinociception by activation of mu (MOR-1), kappa (KOR-1), and delta (DOR-1) opioid receptors. Natural products found in kratom plant, Mitragyna speciosa, represent diverse chemical groups with opioid activity, providing opportunities to better understand opioid pharmacology. Pharmacology studies show that Mitragynine pseudoindoxyl is a mu agonist/delta antagonist opioid with a signaling bias for G-protein-mediated signaling pathways in vitro and which produced potent antinociception in vivo. Respiratory depression assays along with other behavioral testing also showed that some of the major problems …

Identifying Genetic Factors Influencing Sperm Mobility Phenotype In Chicken Using Genome Wide Association Studies, Primordial Germ Cell Transplantation, And Rnaseq., Sohita Ojha

Graduate Theses and Dissertations

Sperm mobility is a major determinant of male fertility in chicken. In spite of low heritability of reproductive traits, sperm mobility has high heritability index which suggests presence of quantitative trait loci (QTLs) governing the trait. Our research focused on three objectives: i) to identify the QTLs affecting low mobility phenotype in chicken, ii) to understand the impact of Sertoli-cells and germ cells interactions in influencing the mobility phenotype and iii) to identify the genes and gene networks differentially expressed in male and female PGCs. To detect the QTLs, genome wide association studies (GWAS) was conducted which revealed the presence …

Development, Evaluation, And Application Of A Novel Error Correction Method For Next Generation Sequencing Data, Isaac Akogwu

Dissertations

Tremendous evolvement in sequencing technologies and the vast availability of data due to decreasing cost of Next-Generation-Sequencing (NGS) has availed scientists the opportunity to address a wide variety of evolutionary and biological issues. NGS uses massively parallel technology to accelerate the process at the expense of accuracy and read length in comparison to earlier Sanger methods. Therefore, computational limitations exist in how much analysis and information can be gleaned from the data without performing some form of error correction.

Error correction process is laborious and consumes a lot of computational resources. Despite the existence of many NGS data error correction …