Bioinformatics Commons^™

Characterization Of A Protozoan Phosducin-Like Protein-3 (Phlp-3) Reveals Conserved Redox Activity, Rachel L. Kooistra, Robin David, Ana C. Ruiz, Kyle J. Haselton, Kaitlyn Kiernan, Andrew M. Blagborough, Ligin Solamen, Kenneth W. Olsen, Catherine Putonti, Stefan M. Kanzok

Biology: Faculty Publications and Other Works

We recently identified three novel thioredoxin-like genes in the genome of the protozoan parasite Plasmodium that belong to the Phosducin-like family of proteins (PhLP). PhLPs are small cytosolic proteins hypothesized to function in G-protein signaling and protein folding. Although PhLPs are highly conserved in eukaryotes from yeast to mammals, only a few representatives have been experimentally characterized to date. In addition, while PhLPs contain a thioredoxin domain, they lack a CXXC motif, a strong indicator for redox activity, and it is unclear whether members of the PhLP family are enzymatically active. Here, we describe PbPhLP-3 as the first phosducin-like protein …

Application Of Graphical Models In Protein-Protein Interactions And Dynamics, Amir Vajdi Hoojghan

Graduate Doctoral Dissertations

Every organism contains a few hundred to thousands of proteins. A protein is made of a sequence of molecular building blocks named amino acids. Amino acids will be referred to as residues. Every protein performs one or more functions in the cell. In order for a protein to do its job, it requires to bind properly to other partner proteins. Many genetic diseases such as cancer are caused by mutations (changes) of specific residues which cause disturbances in the functions of those proteins.

The problem of prediction of protein binding site is a crucial topic in computational biology. A protein …

Characterization Of A Protozoan Phosducin-Like Protein-3 (Phlp-3) Reveals Conserved Redox Activity, Rachel L. Kooistra, Robin David, Ana C. Ruiz, Sean W. Powers, Kyle J. Haselton, Kaitlyn Kiernan, Andrew M. Blagborough, Ligin Solamen, Kenneth W, Olsen, Catherine Putonti, Stefan M. Kanzok

Bioinformatics Faculty Publications

We recently identified three novel thioredoxin-like genes in the genome of the protozoan parasite Plasmodium that belong to the Phosducin-like family of proteins (PhLP). PhLPs are small cytosolic proteins hypothesized to function in G-protein signaling and protein folding. Although PhLPs are highly conserved in eukaryotes from yeast to mammals, only a few representatives have been experimentally characterized to date. In addition, while PhLPs contain a thioredoxin domain, they lack a CXXC motif, a strong indicator for redox activity, and it is unclear whether members of the PhLP family are enzymatically active. Here, we describe PbPhLP-3 as the first phosducin-like protein …

Characterization Of A Protozoan Phosducin-Like Protein-3 (Phlp-3) Reveals Conserved Redox Activity, Rachel L. Kooistra, Robin David, Ana C. Ruiz, Sean W. Powers, Kyle J. Haselton, Kaitlyn Kiernan, Andrew M. Blagborough, Ken W. Olsen, Catherine Putonti, Stefan M. Kanzok

Chemistry: Faculty Publications and Other Works

We recently identified three novel thioredoxin-like genes in the genome of the protozoan parasite Plasmodium that belong to the Phosducin-like family of proteins (PhLP). PhLPs are small cytosolic proteins hypothesized to function in G-protein signaling and protein folding. Although PhLPs are highly conserved in eukaryotes from yeast to mammals, only a few representatives have been experimentally characterized to date. In addition, while PhLPs contain a thioredoxin domain, they lack a CXXC motif, a strong indicator for redox activity, and it is unclear whether members of the PhLP family are enzymatically active. Here, we describe PbPhLP-3 as the first phosducin-like protein …

Polya Db3: A Database Cataloging Polyadenation Sites(Pas) Across Different Species And Their Conservation, Ram Mohan Nambiar

Theses

Polyadenation is an important process occurring in the messenger RNA that involves cleavage of 3 end nascent mRNAs and addition of poly(A) tails. For this thesis,I present PolyA DB3 ,a database cataloging cleavage and polyadenylation sites (PASs) in several genomes specifically for human,mouse,rat and chicken. This database is based on deep sequencing data. PASs are mapped by the 3’ region extraction and deep sequencing (3’READS) method, ensuring unequivocal PAS identification. Large volume of data based on diverse biological samples is used to increase PAS coverage and provide PAS usage information. Strand-specific RNA-seq data were used to extend annotated 3’ ends …

The International Conference On Intelligent Biology And Medicine (Icibm) 2018: Bioinformatics Towards Translational Applications, Xiaoming Liu, Lei Xie, Zhijin Wu, Kai Wang, Zhongming Zhao, Jianhuan Ruan, Degui Zhi

Publications and Research

The 2018 International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held on June 10–12, 2018, in Los Angeles, California, USA. The conference consisted of a total of eleven scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks, which covered a wild range of aspects of bioinformatics, medical informatics, systems biology and intelligent computing. Here, we summarize nine research articles selected for publishing in BMC Bioinformatics.

A New Insight Into Underlying Disease Mechanism Through Semi-Parametric Latent Differential Network Model, Yong He, Jiadong Ji, Lei Xie, Xinsheng Zhang, Fuzhong Xue

Publications and Research

Background

In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous data. However, in real application, we may encounter discrete data or mixed data, which urges us to propose a unified differential network modelling for various data types.

Results

We propose a unified latent Gaussian copula differential network model which provides deeper understanding of the unknown mechanism than that among the observed variables. Adaptive rank-based estimation approaches are proposed with the assumption …

Understanding The Impacts Of Current And Future Environmental Variation On Central African Amphibian Biodiversity, Courtney A. Miller

University of New Orleans Theses and Dissertations

Global climate change is projected to impact multiple levels of biodiversity by imposing strong selection pressures on existing populations, triggering shifts in species distributions, and reorganizing entire communities. The Lower Guineo-Congolian region in central Africa, a reservoir for amphibian diversity, is predicted to be severely affected by future climate change through rising temperatures and greater variability in rainfall. Geospatial modelling can be used to assess how environmental variation shapes patterns of biological variation – from the genomic to the community level – and use these associations to predict patterns of biological change across space and time. The overall goal of …

Minimum Information About An Uncultivated Virus Genome (Miuvig), Simon Roux, Evelien M. Adriaenssens, Bas E. Dutilh, Eugene V. Koonin, Andrew M. Kropinski, Mart Krupovic, Jens H. Kuhn, Rob Lavigne, J Rodney Brister, Arvind Varsani, Clara Amid, Ramy K. Aziz, Seth R. Bordenstein, Peer Bork, Mya Breitbart, Guy R. Cochrane, Rebecca A. Daly, Christelle Desnues, Melissa B. Duhaime, Joanne B. Emerson, François Enault, Jed A. Fuhrman, Pascal Hingamp, Philip Hugenholtz, Bonnie L. Hurwitz, Natalie N. Ivanova, Jessica M. Labonté, Kyung-Bum Lee, Rex R. Malmstrom, Manuel Martinez-Garcia, Ilene Karsch Mizrachi, Hiroyuki Ogata, David Páez-Espino, Marie-Agnès Petit, Catherine Putonti, Thomas Rattei, Alejandro Reyes, Francisco Rodriguez-Valera, Karyna Rosario, Lynn Schriml, Frederik Schulz, Grieg F. Steward, Matthew B. Sullivan, Shinichi Sunagawa, Curtis A. Suttle, Ben Temperton, Susannah G. Tringe, Rebecca Vega Thurber, Nicole S. Webster, Katrine L. Whiteson, Steven W. Whilhelm, K Eric Wommack, Tanja Woyke, Kelly C. Wrighton, Pelin Yilmaz, Takashi Yoshida, Mark J. Young, Natalya Yutin, Lisa Zeigler Allen, Nikos C. Kyrpides, Emiley A. Eloe-Fadrosh

Bioinformatics Faculty Publications

We present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative …

Pasnet: Pathway-Associated Sparse Deepneural Network For Prognosis Prediction From High-Throughput Data, Jie Hao, Youngsoon Kim, Tae-Kyung Kim, Mingon Kang

Faculty and Research Publications

Background: Predicting prognosis in patients from large-scale genomic data is a fundamentally challenging problem in genomic medicine. However, the prognosis still remains poor in many diseases. The poor prognosis maybe caused by high complexity of biological systems, where multiple biological components and their hierarchical relationships are involved. Moreover, it is challenging to develop robust computational solutions with high-dimension, low-sample size data. Results: In this study, we propose a Pathway-Associated Sparse Deep Neural Network (PASNet) that not only predicts patients’ prognoses but also describes complex biological processes regarding biological pathways for prognosis. PASNet models a multilayered, hierarchical biological system of genes …

Mechanistic Characterization Of Resistome And Microbiome Dynamics Across Diverse Microbial Habitats, Andrew John Gasparrini

Arts & Sciences Electronic Theses and Dissertations

Increasing antibiotic resistance in pathogens is a serious public health challenge, with over two million antibiotic resistant infections in the United States leading to at least 23,000 deaths and an estimated $55 billion in excess healthcare and societal costs. Antibiotic resistance has risen steadily in both pathogenic and benign bacteria since antibiotics’ introduction to agriculture and medicine 70 years ago. A dramatic reduction in the number of antibiotics approved for human use has accompanied this rise in antibiotic resistance, leading to the alarming prospect of a post-antibiotic era. Understanding the evolutionary origins, genetic contexts, and molecular mechanisms of antibiotic resistance …

The Splice Is Not Right: Splice-Site-Creating Mutations In Cancer Genomes, Reyka Glencora Jayasinghe

Arts & Sciences Electronic Theses and Dissertations

Accurate interpretation of cancer mutations in individual tumors is a prerequisite for precision medicine. Large-scale sequencing studies, such as The Cancer Genome Atlas (TCGA) project, have worked to address the functional consequences of genomic mutations, with the larger goal of determining the underlying mechanisms of cancer initiation and progression. Many studies have focused on characterizing non-synonymous somatic mutations that alter amino acid sequence, as well as splice disrupting mutations at splice donors and acceptors. Current annotation methods typically classify mutations as disruptors of splicing if they fall on the consensus intronic dinucleotide splice donor, GT, the splice acceptor, AG. Splice …

Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li

Arts & Sciences Electronic Theses and Dissertations

The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is …

Protein Structure-Guided Approaches To Identify Functional Mutations In Cancer, Sohini Sengupta

Arts & Sciences Electronic Theses and Dissertations

Distinguishing driver mutations from passenger mutations within tumor cells continues to be a major challenge in cancer genomics. Many computational tools have been developed to address this challenge; however, they rely heavily on primary protein sequence context and frequency/mutation rate. Rare driver mutations not found in many cancer patients may be missed with these traditional approaches. Additionally, the structural context of mutations on tertiary/quaternary protein structures is not taken into account and may play a more prominent role in determining phenotype and function. This dissertation first presents a novel computational tool called HotSpot3D, which identifies regions of protein structures that …

Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal

Arts & Sciences Electronic Theses and Dissertations

The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific …

A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey

Arts & Sciences Electronic Theses and Dissertations

The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …

Red Panda: A Novel Method For Detecting Variation In Single-Cell Rna Sequencing, Adam Cornish

Theses & Dissertations

Single-cell sequencing enables the rapid acquisition of genomic and transcriptomic data from individual cells to better understand genetic diseases, such as cancer or autoimmune disorders, which are often affected by changes in rare cells. Currently, no existing software is aimed at identifying single nucleotide variations or micro (1-50bp) insertions and deletions in single-cell RNA sequencing (scRNA-seq) data. However, generating high quality data is vital to the study of the aforementioned diseases, among others. Our goal is to create such a tool and use in-house sequencing to validate its effectiveness. Our software employs the unique information found in scRNA-seq data to …

Physella Acuta, Comparative Immunology And Evolutionary Aspects Of Gastropod Immune Function, Jonathan H. Schultz

Biology ETDs

Gastropod immunobiology has benefitted from investigations focused on the planorbid snail Biomphalaria glabrata, intermediate host for the human parasite Schistosoma mansoni. Though such concentrated efforts have elucidated fascinating aspects of invertebrate immunity, they have not provided full knowledge regarding the evolution of immune function among other gastropod species. This dissertation presents the importance of making strategic choices regarding which organisms to select for comparative immunology. Herein, the choice was made to investigate the immunobiology of Physella acuta, a freshwater snail species of the Physidae, a sister family to Planorbidae to which B. glabrata belongs. Benefiting greatly from …

Investigating The Role Of Brachypodium Distachyon Cellulose Synthase 8 In Gluconacetobacter Diazotrophicus Colonization, Xuan Yang

Electronic Thesis and Dissertation Repository

Nitrogen is an essential nutrient for plant growth. Significant amount of nitrogen fertilizer is applied to crop field to maintain high yield. Alternatives to chemical nitrogen fertilizer are needed to reduce the costs of crop production and offset environmental damage. Gluconacetobacter diazotrophicus is a nitrogen fixing bacterium that was originally isolated from sugarcane and has been proposed as a possible biofertilizer for monocot crop production. However, the colonization of G. diazotrophicus in most monocot crops is limited and deep understanding of the response of the host plants to G. diazotrophicus colonization is still lacking. In this study, research was conducted …

Phr: Patient Health Record, Quinn Nelson

Theses/Capstones/Creative Projects

The rapid development of information technology systems has expanded into multiple disciplines and results in systems that are limited by initial design and implementation: the Healthcare Information Technology (HIT) space is no different. The introduction of the Electronic Health Record (EHR) system has changed the way healthcare operates. Initial designs of these systems were focused on serving the needs of insurance companies and healthcare billing departments. Research shows that the design of EHR systems negatively impact provider-patient interactions and the care they receive. This capstone project capitalizes on the collaboration efforts between UNO and UNMC – by joining a research …

Improving Dbnsfp, Mingyao Lu

Dissertations & Theses (Open Access)

IMPROVING dbNSFP

Mingyao Lu, B.S.

Advisory Professor: Xiaoming Liu, Ph.D.

The analysis and interpretation of DNA variation are very important for the Whole Exome studies (WES). Genome research has focused on single nucleotide variants (SNVs). Since indels are as important as SNVs, especially indels in coding regions are often candidates of disease-causing variants, thus, it is necessary to expand the focus to include indel mutations.

The goal of my project is to provide an automatic annotation pipeline to the WES based disease studies project by extending the dbNSFP with a tool for automated indel annotation and deleteriousness prediction. The current …

Functional Consequence Of Psat1 Association On Pkm2'S Inherent Enzymatic Activity., Alexis Avidan Vega

Electronic Theses and Dissertations

Pyruvate kinase M2 (PKM2) is predominantly found in tumors, where it allows the cancer cell to adapt to metabolic conditions through allosteric regulation of its activity. We recently discovered that phosphoserine aminotransferase 1 (PSAT1) associates with and activates PKM2. Here, I sought to affirm PSAT1's ability to increase PKM2 activity through kinetic and association studies of wild-type or mutant PKM2 enzymes. I demonstrate that His-tagged WT and mutant PKM2 enzymes are active, exhibit different kinetics, yet cannot be activated by PSAT1. Comparison studies using untagged WT PKM2 suggest that inclusion of the His-tag disrupts PSAT1 association. In support, pull-down strategies …

Diversification Across A Dynamic Landscape: Phylogeography And Riverscape Genetics Of Speckled Dace (Rhinichthys Osculus) In Western North America, Steven Michael Mussmann

Graduate Theses and Dissertations

Evolution occurs at various spatial and temporal scales. For example, speciation may occur in historic time, whereas localized adaptation is more contemporary. Each is required to identify and manage biodiversity. However, the relative abundance of Speckled Dace (Rhinichthys osculus), a small cyprinid fish in western North America (WNA) and the study species for this dissertation, establishes it an atypical conservation target, particularly when contrasted with the profusion of narrowly endemic forms it displays. Yet, the juxtaposition of ubiquity versus endemism provides an ideal model against which to test hypotheses regarding the geomorphic evolution of WNA. More specifically, it also allows …

Genetic And Epigenetic Investigations On Pulmonary Hypertension Syndrome In Meat Type- Chickens, Khaloud Alzahrani

Graduate Theses and Dissertations

This dissertation presents a collection of studies that investigate the genetic and epigenetic associations to ascites phenotype in broiler chickens. Ascites is a significant metabolic disease associated with fast-growing meat-type chickens (broilers) and is a terminal result of pulmonary hypertension syndrome PHS. It is a multi-factorial syndrome caused by interactions between genetic, physiological, environmental, and managemental factors. It was estimated that ascites accounts for losses of about US$1 billion annually worldwide and for over 25% of broilers mortality. Although traditional and molecular genetic methods in the selection and in performance improvements, has greatly reduced ascites frequency, yet it has not …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations & Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

Confold2: Improved Contact-Driven Ab Initio Protein Structure Modeling, Badri Adhikari, Jianlin Cheng

Badri Adhikari

No abstract provided.

Dna Subway Purple Line Metagenome Analysis, Ray A. Enke

Ray Enke Ph.D.

Thermal And Microbial Effects On Brown Macroalgae: Heat Acclimation And The Biodiversity Of The Microbiome, Charlotte Tc Quigley

Electronic Theses and Dissertations

This dissertation examines effects of stress on brown algal biology from a macroscopic scale by examining the whole aquaculture crops, and at a microscopic level by examining the macroalgal microbiome, across the vertical stress gradient of the intertidal zone and across the latitudes of their biogeographic ranges. Thermal stress negatively affected seedstock gametophytes of the kelp Alaria esculenta isolated from northern and southern locations in Maine. However, previous thermal stress had a positive effect on growth of the next-generation sporophytes. Alaria esculenta has potential as a kelp crop in Maine’s sea vegetable aquaculture sector and implementing this protocol may allow …

A Parallelized Implementation Of Cut-And-Solve And A Streamlined Mixed-Integer Linear Programming Model For Finding Genetic Patterns Optimally Associated With Complex Diseases, Michael Yip-Hin Chan

Theses

With the advent of genetic sequencing, there was much hope of finding the inherited elements underlying complex diseases, such as late-onset Alzheimer’s disease (AD), but it has been a challenge to fully uncover the necessary information hidden in the data. A likely contributor to this failure is the fact that the pathogenesis of most complex diseases does not involve single markers working alone, but patterns of genetic markers interacting additively or epistatically. But as we move upwards beyond patterns of size two, it quickly becomes computationally infeasible to examine all combinations in the solution space. A common solution to solving …

Multi-Resolution Analysis Of Large Molecular Structures And Interactions, Kasra Manavi

Computer Science ETDs

Simulation of large molecular structures and their interactions has become a major component of modern biomolecular research. Methods to simulate these type of molecules span a wide array of resolutions, from all atom molecular dynamics to model interaction energetics to systems of linear equations to evaluate population kinetics. In recent years, there has been an acceleration of molecular structural information production, primarily from x-ray crystallography and electron microscopy. This data has provided modelers the ability to produce better representations of these molecular structures. The purpose of this research is to take advantage of this information to develop multi-resolution models for …