Computational Biology Commons^™

Pathway-Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Jem Bagchee-Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

No abstract provided.

Quantifying Structure And Variation In Complex Phylogenetic Data, Genevieve Geraldine Mount

LSU Doctoral Dissertations

Identifying the source and structure of variation in nature is crucial to understanding fundamental aspects of evolution. Despite a recent plethora of genetic and morphological data, many interesting questions about the relationships between different groups remain unresolved. My dissertation evaluates three approaches for identifying and quantifying the variation within phylogenetic datasets. Characterizing variation within datasets and across analytical methods gives insight into biologically interesting characters, unusual evolutionary processes, and areas for model improvement.

Network-based community detection approaches offer a powerful tool to describe variation in phylogenetic signal across the genome (i.e., gene tree variation). In Chapter 2, I investigate the …

Linking Crude Oil And Dispersant Effects To Gene Expression Of Marine Sponge Cinachyrella, Yvain Desplat

All HCAS Student Capstones, Theses, and Dissertations

Because of their filter-feeding lifestyle, sponges (Phylum Porifera) have shown to be bio-accumulators of heavy metals, and bio-monitors for polychlorobiphenyl (PCB) contaminants. Furthermore, marine sponges have been shown to be regulators of reef ecosystems by fulfilling many ecological functions. However, very little is known about their behavior in the face of environmental changes. Consequently, our lab has developed the reef sponge Cinachyrella spp. as novel experimental model. We have designed an experiment to study the effects of WAF (Water Accommodated Fraction), Corexit 9500 dispersant, and CE-WAF (Chemically Enhanced Water Accommodated Fraction)mixtures, in an effort to mimic the conditions of the …

Identification Of Trim24 Domain Essentiality In Primary Trim24coe Carcinosarcoma Cell Lines, Cem Dede

Dissertations and Theses (Open Access)

Regulation of transcriptional control is a critical feature for organismal development and survival. Because of its effects on chromatin-controlled expression, disruptions of this delicately tuned mechanism are an important factor in development of tumorigenesis. Therefore, there is a growing interest in targeting these control mechanisms for their potential therapeutic values.

Our lab previously discovered the epigenetic regulator function of Tripartite motif protein 24 (TRIM24) through its H3K4me0 and H3K23ac dual histone signature reader function, its negative regulatory effect on the p53 tumor suppressor, in addition to its shown oncogenic driving capacity on immortalized mammary epithelial cells when overexpressed. Although TRIM24 …

Statistical Methods For Resolving Intratumor Heterogeneity With Single-Cell Dna Sequencing, Alexander Davis

Dissertations and Theses (Open Access)

Tumor cells have heterogeneous genotypes, which drives progression and treatment resistance. Such genetic intratumor heterogeneity plays a role in the process of clonal evolution that underlies tumor progression and treatment resistance. Single-cell DNA sequencing is a promising experimental method for studying intratumor heterogeneity, but brings unique statistical challenges in interpreting the resulting data. Researchers lack methods to determine whether sufficiently many cells have been sampled from a tumor. In addition, there are no proven computational methods for determining the ploidy of a cell, a necessary step in the determination of copy number. In this work, software for calculating probabilities from …

Statistical Inference Of Adaptation At Multiple Genomic Scales Using Supervised Classification And A Hidden Markov Model, Lauren A. Sugden

Biology and Medicine Through Mathematics Conference

No abstract provided.

Identification And Analysis Of Feather Degrading Bacteria: A Search For Keratinase Genes, Nehal Navali

Honors Scholar Theses

Over two million tons of feather waste is generated annually by the poultry industry, the majority of which goes into landfills due to the difficulty of degrading its major component keratin. Although a portion of feather waste is eliminated via incineration or chemical treatment, the use of Feather Degrading Bacteria (FDB) has been proposed as a cheap and eco-friendly alternative. FDBs have been consistently isolated from the feather microbiome of birds and contain genes coding for the specialized protein keratinase which is able to degrade feathers. By doing so, feather waste, which is rich in nutrients, can be repurposed as …

Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren Mcgee, Jane Y. Wu

Student Publications & Research

Glioblastoma (GBM) is a grade IV astrocytoma formed primarily from cancerous astrocytes and sustained by intense angiogenesis. GBM often causes non-specific symptoms, creating difficulty for diagnosis. This study aimed to utilize machine learning techniques to provide an accurate one-year survival prognosis for GBM patients using clinical and genomic data from the Chinese Glioma Genome Atlas. Logistic regression (LR), support vector machines (SVM), random forest (RF), and ensemble models were used to identify and select predictors for GBM survival and to classify patients into those with an overall survival (OS) of less than one year and one year or greater. With …

The Host Gatekeeper: Using The Flagellar Pathway To Understand Symbiont Host Adaptation, Adam R. Pollio

Graduate Theses, Dissertations, and Problem Reports (ETD)

The acquisition of microbial partners is a strategy used by a diverse group of arthropods to overcome ecological barriers that might normally make certain niches uninhabitable. The unique phylogenetic opportunities attainable from the natural experiment of the Sodalis-allied clade allow for better understanding of how molecular structures evolve through time. Here, we focus on the evolution of the flagellar synthesis pathway, due to its complexity and ability to diverge in response to ecological pressures. We used this molecular pathway and natural experiment to show that normal evolutionary outcomes associated with symbiosis (i.e., genome reduction) do not explain the predicted conservation …

A Transcriptomic Exploration Of Hawaiian Drosophilid Development And Evolution, Madeline M. Chenevert

LSU New Orleans Theses and Dissertations

One in four known species of fruit flies inhabit the Hawaiian Islands. From a small number of colonizing flies, a wide range of species evolved, some of which managed to reverse-colonize other continental environments. In order to explore the developmental pathways, which separate the Hawaiian Drosophila proper and the Scaptomyza group that contains reverse-colonized species, the transcriptomes of two better-known species in each group, Scaptomyza anomala and Drosophila grimshawi, were analyzed to find changes in gene expression between the two groups. This study describes a novel transcriptome for S. anomala studies as well as unusual changes in gene expression …

Chasing The Genetics Of Ascites In Broilers Using Whole Genome Resequencing, Alia Parveen

Graduate Theses and Dissertations

We are using whole genome resequencing to identify chromosomal regions associated with resistance or susceptibility to ascites, a form of pulmonary hypertension syndrome, meat-type chickens. Previous Genome Wide Association Studies (GWAS) based on Single Nucleotide Polymorphisms (SNPs) have identified regions on chromosomes 2, 9 and Z. Despite several GWAS and further genotyping, there are no reliable or potential markers for ascites phenotype. We have completed screening of Copy Number Variations (CNVs) and Single Nucleotide Polymorphisms in ascites resistant and susceptible birds from the relaxed, REL, line derived from a commercial elite broiler line. DNA samples from resistant and susceptible birds …

Characterization And Amplification Of Retrotransposable Elements Platy-1 And Alu In The Cebidae Lineage Of Platyrrhine Primates, Jessica Storer

LSU Doctoral Dissertations

Alu mobile elements are much more than “junk DNA”. Inherent properties such as high copy number, small ~300 bp size, and their nearly homoplasy-free nature make these elements particularly useful in resolving primate phylogenies. In addition, shared sequence features and identity with the Alu element allow for discovery of new SINE retrotransposons, such as the Platyrrhine-limited Platy-1 element. Building on previous research of subfamily analysis, the Platy-1 and Alu elements can be used not only to explore the controversial New World monkey (NWM) phylogeny, but also the mode and tempo of their amplification in different primate genera and species.

Chapter …

Phylogenetic Trees And Networks Can Serve As Powerful And Complementary Approaches For Analysis Of Genomic Data, Christopher Blair, Cécile Ané

Publications and Research

Genomic data have had a profound impact on nearly every biological discipline. In systematics and phylogenetics, the thousands of loci that are now being sequenced can be analyzed under the multispecies coalescent model (MSC) to explicitly account for gene tree discordance due to incomplete lineage sorting (ILS). However, the MSC assumes no gene flow post divergence, calling for additional methods that can accommodate this limitation. Explicit phylogenetic network methods have emerged, which can simultaneously account for ILS and gene flow by representing evolutionary history as a directed acyclic graph. In this point-of-view we highlight some of the strengths and limitations …

Association Of Copy Number Variations With Chronic Hepatitis B In Chinese Population, Fang Niu

Capstone Experience: Master of Public Health

With one third of the Hepatitis B virus (HBV) infection population of the world, chronic Hepatitis B (CHB) has become a top burden in China. CHB is a lifelong infection with HBV which can cause serious health problems, like cirrhosis, liver cancer or even death. HBV infection is known to result in various clinical conditions, including asymptomatic HBV carriers to chronic hepatitis and primary hepatocellular carcinoma. Several studies have shown that host genetic susceptibility could be an important factor that determines these various outcomes of HBV infection. Many Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) have been associated …

Molecular Consequences Of High Taz Expression In Gliomas, Visweswaran Ravikumar

Dissertations and Theses (Open Access)

Diffuse high grade gliomas are complex and lethal neoplasms of the adult central nervous system that are driven by a range of genetic and epigenetic alterations. Molecular classification of these tumors has identified different transcriptional subtypes, the most notable being Proneural (PN) and Mesenchymal (MES) classes. The most aggressive forms of the disease have a Mesenchymal expression signature, with reported PN-to-MES transition occurring with tumor progression. Master regulatory analysis has identified the transcriptional co-activator TAZ (WWTR1) as a major driver of the MES transition. Overexpression of this single protein in glioma stem cells has been shown to drive a transition …

High-Performance Computing Frameworks For Large-Scale Genome Assembly, Sayan Goswami

LSU Doctoral Dissertations

Genome sequencing technology has witnessed tremendous progress in terms of throughput and cost per base pair, resulting in an explosion in the size of data. Typical de Bruijn graph-based assembly tools demand a lot of processing power and memory and cannot assemble big datasets unless running on a scaled-up server with terabytes of RAMs or scaled-out cluster with several dozens of nodes. In the first part of this work, we present a distributed next-generation sequence (NGS) assembler called Lazer, that achieves both scalability and memory efficiency by using partitioned de Bruijn graphs. By enhancing the memory-to-disk swapping and reducing the …

Simplicity Diffexpress: A Bespoke Cloud-Based Interface For Rna-Seq Differential Expression Modeling And Analysis, Cintia C. Palu, Marcelo Ribeiro-Alves, Yanxin Wu, Brendan Lawlor, Pavel V. Baranov, Brian Kelly, Paul Walsh

Department of Computer Science Publications

One of the key challenges for transcriptomics-based research is not only the processing of large data but also modeling the complexity of features that are sources of variation across samples, which is required for an accurate statistical analysis. Therefore, our goal is to foster access for wet lab researchers to bioinformatics tools, in order to enhance their ability to explore biological aspects and validate hypotheses with robust analysis. In this context, user-friendly interfaces can enable researchers to apply computational biology methods without requiring bioinformatics expertise. Such bespoke platforms can improve the quality of the findings by allowing the researcher to …

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

Mrub_3019 Casa Gene Is An Ortholog To E. Coli B2760, Kelsey Heiland, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This research is part of the Meiothermus ruber genome annotation project which aims to predict gene function with various bioinformatics tools. We investigated the function of Mrub_3019, which encodes the CasA protein involved in the multi-subunit effector complex for the CRISPR-Cas immunity system and predicted it to be an ortholog of E. coli K12 MG1655 b2760 (casA). We predicted that Mrub_3019 encodes the protein CasA, which is involved in PAM recognition of CRISPR interference pathway. Foreign DNA will bind to CasA, which signals Cas3 for helicase-mediated DNA degradation. Our hypothesis is supported by low E-values for pairwise alignment in NCBI …

Mrub_3015 Is Orthologous To The B2757 Gene Found In Escherichia Coli Coding For Casd, Ramona Collins, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of the gene Mrub_3015, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system. We predict that Mrub_3015 (DNA coordinates 3055550...3056245) encodes the the CRISPR-associated protein cas5, which is integral in maintaining the crRNA-DNA structure, keeping the complex from base pairing with the target phage DNA. Our hypothesis is supported by identical hits for Mrub_3015 and b2527 to the KEGG, Pfam, TIGRfam, CDD and PDB databases as well as a …

Mrub_3018 Is Orthologous To E. Coli B2759 (Casb), Kyle Parker, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We studied the biological activity of the Mrub_3018 gene, which we hypothesize is orthologous to E. coli gene B2759. We predicted that Mrub_3018(DNA coordinates 3057916… 3058524) encodes the protein CasB. CasB is a protein in the CRISPR CASCADE that will function as a structural protein. When the rest of the proteins form an “S” formation CasB will connect the front and back of the “S” creating a back bone for the structure. It will help bind DNA …

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

Theses and Dissertations

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.

A Novel Pathway-Based Distance Score Enhances Assessment Of Disease Heterogeneity In Gene Expression, Yunqing Liu, Xiting Yan

Yale Day of Data

Distance-based unsupervised clustering of gene expression data is commonly used to identify heterogeneity in biologic samples. However, high noise levels in gene expression data and the relatively high correlation between genes are often encountered, so traditional distances such as Euclidean distance may not be effective at discriminating the biological differences between samples. In this study, we developed a novel computational method to assess the biological differences based on pathways by assuming that ontologically defined biological pathways in biologically similar samples have similar behavior. Application of this distance score results in more accurate, robust, and biologically meaningful clustering results in both …

Mrub_3014 Is Orthologous To B2756, Samir Abdelkarim, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of the gene Mrub_3014, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system. We predict that Mrub_3014 (DNA coordinates 3054943..3055575) encodes CRISPR-associated protein Cse3/case which function as an endonuclease. Our hypothesis is supported by identical hits for Mrub_3014 and b2756 to the KEGG, Pfam, TIGRfam, CDD and PDB databases, as well as a low E-value for a pairwise NCBI BLAST comparison. Both protein products are predicted to be localized …

M. Ruber Mrub_3013 Is Orthologous To E. Coli B2755, Laura Butcher, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of gene Mrub_3013, which we hypothesize is orthologous to b2755 in E. coli K12 MG1655 (a.k.a. Cas1). We investigated the biological function of a gene with the M. ruber locus tag of Mrub_3013, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system in M. ruber. We predict that Mrub_3013 (DNA coordinates 3,053,978-3,054,940) encodes the protein Cas1 which as part of the CRISPR-Cas system, selects and cuts the foreign …

Mrub_3020, A Paralog Of Mrub_1489, Is Orthologous To E. Coli Casc (Locus Tag B2761), Alfred Dei-Ampeh, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological functions of two genes: mrub_3020 and mrub_1489. We make two hypotheses in this investigation: a) mrub_3020 is orthologous to the gene b2761 in E. coli K12 MG1655 (a.k.a. casC); b) mrub_1489 is a paralog of mrub_3020. We also predict that the two genes encode unique proteins: mrub_3020 with DNA coordinates 3060491…3063190 encodes a CRISPR – associated helicase (Cas3) that supports the Cascade complex of the CRISPR – Cas adaptive immune system …

Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu

Biochemistry Publications

Background: The distribution and composition of cis-regulatory modules composed of transcription factor (TF) binding site (TFBS) clusters in promoters substantially determine gene expression patterns and TF targets. TF knockdown experiments have revealed that TF binding profiles and gene expression levels are correlated. We use TFBS features within accessible promoter intervals to predict genes with similar tissue-wide expression patterns and TF targets using Machine Learning (ML). Methods: Bray-Curtis Similarity was used to identify genes with correlated expression patterns across 53 tissues. TF targets from knockdown experiments were also analyzed by this approach to set up the ML framework. TFBSs were …

Association Genetics And Local Adaptation Of Populus Trichocarpa Torr. & Gray, Hari Bahadur Chhetri

Graduate Theses, Dissertations, and Problem Reports (ETD)

A major goal in plant science is overcoming the recalcitrance of plant biomass to cellulose extraction, to enable efficient production of cellulosic biofuel. We have started to understand the genetic basis of some important traits such as cell wall chemistry, but we do not know anything about the key structural and functional traits such as wood anatomy that greatly affect plant biomass recalcitrance. Furthermore, biofuel feedstocks have to be adapted to varied environmental conditions to ensure high productivity in plantations, but little is known about the molecular mechanisms underlying local adaptation. With the advancement in sequencing and genotyping technologies, association …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …