Computational Biology Commons^™

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 …

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations and Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …

Linking Taxonomic Diversity And Trophic Function: A Graph-Based Theoretical Approach, Marcella M. Jurotich, Kaitlyn Dougherty, Barbara Hayford, Sally Clark

Transactions of the Nebraska Academy of Sciences and Affiliated Societies

The purpose of this study is to develop a novel, visual method in analyzing complex functional trait data in freshwater ecology. We focus on macroinvertebrates in stream ecosystems under a gradient of habitat degradation and employ a combination of taxonomic and functional trait diversity analyses. Then we use graph theory to link changes in functional trait diversity to taxonomic richness and habitat degradation. We test the hypotheses that: 1) taxonomic diversity and trophic functional trait diversity both decrease with increased habitat degradation; 2) loss of taxa leads to a decrease in trophic function as visualized using a bipartite graph; and …

The Role Of Histone H2a.Z Abundance In Modulating Responses To Phosphorus Deficiency In Rice, Sara Zahraeifard

LSU Doctoral Dissertations

Histone variants contribute to chromatin complexity by creating specialized nucleosomes. Here, to investigate the pattern of H2A.Z histone variant distribution and its role in modulating gene expression in rice (Oryza sativa L.), we performed genome-wide profiling of ARP6-dependent H2A.Z deposition in rice seedlings. We demonstrated that under controlled conditions, the majority of H2A.Z deposition is within protein-coding genes (PCG), and the most highly expressed genes are enriched with H2A.Z at their 5’ ends near the transcription start site (TSS), whereas the medium- to low-expressed genes contain H2A.Z across the entire gene. Based on H2A.Z deposition, we categorized genes into …

Cryptic Diversity And Discordance In Single‐Locus Species Delimitation Methods Within Horned Lizards (Phrynosomatidae: Phrynosoma), Christopher Blair, Robert W. Bryson Jr.

Publications and Research

Biodiversity reduction and loss continues to progress at an alarming rate, and thus there is widespread interest in utilizing rapid and efficient methods for quantifying and delimiting taxonomic diversity. Single-locus species-delimitation methods have become popular, in part due to the adoption of the DNA barcoding paradigm. These techniques can be broadly classified into tree-based and distance-based methods depending on whether species are delimited based on a constructed genealogy. Although the relative performance of these methods has been tested repeatedly with simulations, additional studies are needed to assess congruence with empirical data. We compiled a large data set of mitochondrial ND4 …

Chromosome Conformation In Context, James Taylor

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Cage: A Tool For Identifying Genes With Correlated Spatiotemporal Expression, Basheer Becerra

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Study Of Antidepressant Molecular Structure Leading To Safer Dosing, Meera Garg

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Phylogenetic Evidence From Freshwater Crayfishes That Cave Adaptation Is Not An Evolutionary Dead-End., David B Stern, Jesse Breinholt, Carlos Pedraza-Lara, Marilú López-Mejía, Christopher L Owen, Heather Bracken-Grissom, James W Fetzner, Keith A Crandall

Computational Biology Institute

Caves are perceived as isolated, extreme habitats with a uniquely specialized biota, which long ago led to the idea that caves are "evolutionary dead-ends." This implies that cave-adapted taxa may be doomed for extinction before they can diversify or transition to a more stable state. However, this hypothesis has not been explicitly tested in a phylogenetic framework with multiple independently evolved cave-dwelling groups. Here, we use the freshwater crayfish, a group with dozens of cave-dwelling species in multiple lineages, as a system to test this hypothesis. We consider historical patterns of lineage diversification and habitat transition as well as current …

Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta

Biomedical Sciences ETDs

This dissertation explores the effects of heterogeneity across different biological scales in cancer as well as normal cells. At the tissue scale, we investigated the variability present in the tumor microenvironment and its effect on patient chemotherapeutic outcomes using a mathematical model of drug transport. We found that parameters such as tumor blood perfusion and radius of blood vessel had an impact on the tumor cytotoxicity. This indicated that the physical microenvironment of the tumor is an important regulator of the tumor response to chemotherapy. At the cellular scale, we investigated the heterogeneity present on the membrane landscape of ErbB2 …

A Combined Computational Strategy Of Sequence And Structural Analysis Predicts The Existence Of A Functional Eicosanoid Pathway In Drosophila Melanogaster, Michael Scarpati

Dissertations, Theses, and Capstone Projects

With increased understanding of their roles in signal transduction and metabolism, eicosanoids have emerged as important players in human health and disease. Mammalian prostanoids and related lipid mediators perform varied functions in different tissues and organs. Synthesized through the oxygenation of C20 polyunsaturated fatty acids, mammalian eicosanoids are both pro- and anti-inflammatory. The physiological contexts in which eicosanoid family members act at the cellular level are not well understood. In this study, we examined whether the genome of Drosophila melanogaster, a powerful model for innate immunity and inflammation, codes for the enzymes required for eicosanoid biosynthesis. We report the …

Computational Investigation Of The Pore Formation Mechanism Of Beta-Hairpin Antimicrobial Peptides, Richard Lipkin

Dissertations, Theses, and Capstone Projects

β-hairpin antimicrobial peptides (AMPs) are small, usually cationic peptides that provide innate biological defenses against multiple agents. They have been proposed as the basis for novel antibiotics, but their pore formation has not been directly observed on a molecular level. We review previous computational studies of peptide-induced membrane pore formation and report several new molecular dynamics simulations of β-hairpin AMPs to elucidate their pore formation mechanism. We simulated β-barrels of various AMPs in anionic implicit membranes, finding that most of the AMPs’ β-barrels were not as stable as those of protegrin. We also performed an optimization study of protegrin β-barrels …

Comparative Phylogeographic, Population Genomic, And Selection Inference With Development Of Hierarchical Co-Demographic Models, Alexander Xue

Dissertations, Theses, and Capstone Projects

Comparing demographic histories across assemblages of populations, species, and sister pairs has been a focus in phylogeography since its inception. Initial approaches utilized organelle genetic data and involved qualitative comparisons of genetic patterns for evaluating hypotheses of shared evolutionary responses to past environmental changes. This endeavor has progressed with coalescent model-based statistical techniques and advances in next-generation sequencing, yet there remains a need for methods that can analyze aggregated genomic-scale data from non-model organisms within a unified framework that considers individual taxon uncertainty and variance. To this end, the aggregate site frequency spectrum (aSFS), an expansion of the site frequency …

Itraq-Based Proteomics Analysis And Network Integration For Kernel Tissue Development In Maize, Long Zhang, Yongbin Dong, Qilei Wang, Chunguang Du, Wenwei Xiong, Xinyu Li, Sailan Zhu, Yuling Li

Department of Biology Faculty Scholarship and Creative Works

Grain weight is one of the most important yield components and a developmentally complex structure comprised of two major compartments (endosperm and pericarp) in maize (Zea mays L.), however, very little is known concerning the coordinated accumulation of the numerous proteins involved. Herein, we used isobaric tags for relative and absolute quantitation (iTRAQ)-based comparative proteomic method to analyze the characteristics of dynamic proteomics for endosperm and pericarp during grain development. Totally, 9539 proteins were identified for both components at four development stages, among which 1401 proteins were non-redundant, 232 proteins were specific in pericarp and 153 proteins were specific in …

Machine Learning Based Protein Sequence To (Un)Structure Mapping And Interaction Prediction, Sumaiya Iqbal

LSU New Orleans Theses and Dissertations

Proteins are the fundamental macromolecules within a cell that carry out most of the biological functions. The computational study of protein structure and its functions, using machine learning and data analytics, is elemental in advancing the life-science research due to the fast-growing biological data and the extensive complexities involved in their analyses towards discovering meaningful insights. Mapping of protein’s primary sequence is not only limited to its structure, we extend that to its disordered component known as Intrinsically Disordered Proteins or Regions in proteins (IDPs/IDRs), and hence the involved dynamics, which help us explain complex interaction within a cell that …

Testing The Independence Hypothesis Of Accepted Mutations For Pairs Of Adjacent Amino Acids In Protein Sequences, Jyotsna Ramanan, Peter Revesz

School of Computing: Faculty Publications

Evolutionary studies usually assume that the genetic mutations are independent of each other. However, that does not imply that the observed mutations are independent of each other because it is possible that when a nucleotide is mutated, then it may be biologically beneficial if an adjacent nucleotide mutates too. With a number of decoded genes currently available in various genome libraries and online databases, it is now possible to have a large-scale computer-based study to test whether the independence assumption holds for pairs of adjacent amino acids. Hence the independence question also arises for pairs of adjacent amino acids within …

Tumor Necrosis Factor Dynamically Regulates The Mrna Stabilome In Rheumatoid Arthritis Fibroblast-Like Synoviocytes, Konstantinos Loupasakis, David Kuo, Upneet K. Sokhi, Christopher Sohn, Bethany Syracuse, Eugenia G. Giannopoulou, Sung Ho Park, Hyelim Kang, Gunnar Rätsch, Lionel B. Ivashkiv, George D. Kalliolias

Publications and Research

During rheumatoid arthritis (RA), Tumor Necrosis Factor (TNF) activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS. We found that TNF induces a biphasic gene expression program: initially, the inducible transcriptome consists primarily of unstable transcripts but progressively switches …

Transcriptomic Differentiation Underlying Marine‐To‐Freshwater Transitions In The South American Silversides Odontesthes Argentinensis And O. Bonariensis (Atheriniformes), Lily Hughes, Gustavo Somoza, Bryan Nguyen, James Bernot, Mariano Gonzalez-Castro, Juan Martin Diaz De Astarloa, Guillermo Orti

Computational Biology Institute

Salinity gradients are critical habitat determinants for freshwater organisms. Silverside fishes in the genus Odontesthes have recently and repeatedly transitioned from marine to freshwater habitats, overcoming a strong ecological barrier. Genomic and transcriptomic changes involved in this kind of transition are only known for a few model species. We present new data and analyses of gene expression and microbiome composition in the gills of two closely related silverside species, marine O. argentinensis and freshwater O. bonariensis and find more than three thousand transcripts differentially expressed, with osmoregulatory/ion transport genes and immune genes showing very different expression patterns across species. Interspecific …

Rnaseq Analysis Of The Drosophila Response To The Entomopathogenic Nematode Steinernema., Shruti Yadav, Sean Daugherty, Amol Carl Shetty, Ioannis Eleftherianos

Computational Biology Institute

Drosophila melanogaster is an outstanding model to study the molecular and functional basis of host-pathogen interactions. Currently, our knowledge of microbial infections in D. melanogaster is well understood; however, the response of flies to nematode infections is still in its infancy. Here, we have used the potent parasitic nematode Steinernema carpocapsae, which lives in mutualism with its endosymbiotic bacteria Xenorhabdus nematophila, to examine the transcriptomic basis of the interaction between D. melanogaster and entomopathogenic nematodes. We have employed next-generation RNA sequencing (RNAseq) to investigate the transcriptomic profile of D. melanogaster larvae in response to infection by S. carpocapsae symbiotic (carrying …

Estimation Of The True Evolutionary Distance Under The Fragile Breakage Model., Nikita Alexeev, Max A Alekseyev

Computational Biology Institute

BACKGROUND: The ability to estimate the evolutionary distance between extant genomes plays a crucial role in many phylogenomic studies. Often such estimation is based on the parsimony assumption, implying that the distance between two genomes can be estimated as the rearrangement distance equal the minimal number of genome rearrangements required to transform one genome into the other. However, in reality the parsimony assumption may not always hold, emphasizing the need for estimation that does not rely on the rearrangement distance. The distance that accounts for the actual (rather than minimal) number of rearrangements between two genomes is often referred to …

Isolation And Comparative Genomic Analysis Of Final Third Of Satis Genome, Kelly Hartigan, Nicole Curnutt, Matthew Mcdermut

Undergraduate Research Symposium Posters

A highly novel Streptomyces phage, Satis, was isolated from a direct environmental sample collected from outside Danforth House on the Washington University campus. Satis infects bacterial species Streptomyces lividans producing pinpoint, cloudy plaques less than 1mm in diameter. Electron microscope data shows rare atypical physical features. Rather than the common octahedral capsid shape, Satis has a prolate head with visible cross-linked hexagonal protein structure and average measurements of 285 nm by 47 nm with a long, flexible tail measuring 268 nm. Upon sequencing, it was found that Satis contains the longest phage genome discovered to date through the SEA-PHAGE program …

Using Mathematical Models Of Biological Processes In Genome-Wide Association Studies Of Psychiatric Disorders, Amy Cochran

Biology and Medicine Through Mathematics Conference

No abstract provided.

Transcriptomic Effects Of Dispersed Oil In A Non-Model Decapod Crustacean, Hernan Vazquez-Miranda, Brent Thoma, Juliet Wong, Darryl Felder, Keith A. Crandall, Heather Bracken-Grissom

Computational Biology Institute

Background. Oil spills are major environmental disasters. Dispersants help control spills, as they emulsify oil into droplets to speed bioremediation. Although dispersant toxicity is controversial, the genetic consequences and damages of dispersed oil exposure are poorly understood. We used RNA-seq to measure gene expression of flatback mudcrabs (Eurypanopeus depressus, Decapoda, Brachyura, Panopeidae) exposed to dispersed oil.

Methods. Our experimental design included two control types, oil-only, and oil-dispersant treatments with three replicates each. We prepared 100 base pair-ended libraries from total RNA and sequenced them in one Illumina HiSeq2000 lane. We assembled a reference transcriptome with all replicates per treatment, …

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations and Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …