Life Sciences Commons^™

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Drug Repurposing Using Gene Expression Data Mining, Yue Qiu

Dissertations, Theses, and Capstone Projects

The conventional drug discovery process that employs the "one disease, one target, one drug'' paradigm is expensive, time-consuming, and has a high rate of failure for multi-genic complex diseases. An alternative approach to drug discovery is to repurpose an existing drug that has been used to treat some medical conditions. Drug repurposing is considered a promising method due to its accelerated the process of drug discovery and lower overall cost and risk.

Drug-perturbed gene expression profiles are powerful phenotype readouts of biological systems, and they have been widely used in drug repurposing studies. However, the existing drug-perturbed gene expression datasets …

Illuminating The Drivers Of Genomic Diversification In Lamprologine Cichlids Of The Lower Congo River, Naoko P. Kurata

Dissertations, Theses, and Capstone Projects

Freshwater fishes are extraordinarily diverse, considering their available habitats represent a tiny proportion of the earth’s surface. Rivers connect heterogeneous habitats in a linear form and provide excellent simplified models to understand how aquatic biodiversity evolves. In particular, the lower Congo River (LCR) in west Central Africa consists of a dynamic hydroscape exhibiting extraordinary aquatic biodiversity, endemicity, and morphological and ecological specialization. This system is thus an excellent natural laboratory for understanding complex speciation and population diversification processes. In my research, I explore various drivers of diversification, and adaptive evolution in rheophilic lamprologine cichlids endemic to the LCR, including Lamprologus …

Genomic Insights Into Mechanisms Of Microbial Evolution And Evolution-Inspired Strategies To Combat Pathogen Diversity, Saymon Akther

Dissertations, Theses, and Capstone Projects

We live in an era of emerging infectious diseases that are increasingly common, rapidly spreading, and gravely devastating. Lyme disease, caused by bacteria belonging to the genus Borreliella, is rapidly rising in the Northern Hemisphere because of geographic range expansion of both the tick vectors and the pathogens. Evolutionary comparative analysis of Borreliella genomes is a key to understanding the phylogeographic history and mechanisms of their global diversification. Moreover, genomic variations in Borreliella associated with human pathogenicity, e.g., at loci encoding cell-surface antigens interacting with the vertebrate hosts, have not been fully identified. Similarly, the ongoing COVID-19 pandemic, caused …

Deepreal: A Deep Learning Powered Multi-Scalemodeling Framework For Predicting Out-Of-Distributionligand-Induced Gpcr Activity, Tian Cai, Kyra Alyssa Abbu, Yang Liu, Lei Xie

Publications and Research

Motivation Drug discovery has witnessed intensive exploration of predictive modeling of drug–target physical interactions over two decades. However, a critical knowledge gap needs to be filled for correlating drug–target interactions with clinical outcomes: predicting genome-wide receptor activities or function selectivity, especially agonist versus antagonist, induced by novel chemicals. Two major obstacles compound the difficulty on this task: known data of receptor activity is far too scarce to train a robust model in light of genome-scale applications, and real-world applications need to deploy a model on data from various shifted distributions.

Results To address these challenges, we have developed an end-to-end …

An In Silico Approach To Investigate The Structural And Biochemical Basis Of The Rna Binding Functions Of Nucleolin, Avdar San

Dissertations, Theses, and Capstone Projects

Nucleolin (NCL) is a stress responsive multifunctional nucleolar protein and accounts for 10% of the total nucleolar protein content. NCL belongs to the class of RNA binding proteins (RBPs) that regulate many important cellular processes through their interactions with different RNA molecules. The dysregulation of RBPs and the RNA metabolism pathways they intersect is a known driver of tumorigenesis. NCL regulates ribosome biogenesis, chromatin remodeling, microRNA processing, and gene expression on multiple levels. The RNA-protein interactions of NCL are primarily driven by its four RNA binding domains (RBDs). NCL is known to interact with a growing list of primary-miRNA (pri-miRNA) …

Democratizing Bioinformatics Through Easily Accessible Software Platforms For Non-Experts In The Field, Konstantinos Krampis

Publications and Research

No abstract provided.

Population Structure Of The Lizard Ecpleopus Gaudichaudii Coincides With A Biogeographic Barrier - The Doce River, Alexander J. Garretson

Dissertations and Theses

Intraspecific genetic variation is an integral component of diversification and the accumulation of biodiversity. The degree to which isolated populations of the same species are genetically structured in geographical space is impacted by a variety of mechanisms. In this study, I document patterns and discuss possible drivers of genetic structure within Ecpleopus gaudichaudii, a lizard species endemic to the Atlantic Forest of Brazil. For that, I assembled ddRadseq sequences from 48 individuals across much of the range of the E. gaudichaudii and analyzed its population structure. I created an intraspecific phylogeny for this group utilizing RAxML and conducted a …

Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski

Dissertations, Theses, and Capstone Projects

Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

A Cross-Level Information Transmission Network Forhierarchical Omics Data Integration And Phenotypeprediction From A New Genotype, Di He, Lei Xie

Publications and Research

Motivation: An unsolved fundamental problem in biology is to predict phenotypes from a new genotype under environmental perturbations. The emergence of multiple omics data provides new opportunities but imposes great challenges in the predictive modeling of genotype-phenotype associations. Firstly, the high-dimensionality of genomics data and the lack of coherent labeled data often make the existing supervised learning techniques less successful. Secondly, it is challenging to integrate heterogeneous omics data from different resources. Finally,few works have explicitly modeled the information transmission from DNA to phenotype, which involves multiple intermediate molecular types. Higher-level features (e.g. gene expression) usually have stronger discriminative …

Graph-Theoretic Partitioning Of Rnas And Classification Of Pseudoknots-Ii, Louis Petingi

Publications and Research

Dual graphs have been applied to model RNA secondary structures with pseudoknots, or intertwined base pairs. In previous works, a linear-time algorithm was introduced to partition dual graphs into maximally connected components called blocks and determine whether each block contains a pseudoknot or not. As pseudoknots can not be contained into two different blocks, this characterization allow us to efficiently isolate smaller RNA fragments and classify them as pseudoknotted or pseudoknot-free regions, while keeping these sub-structures intact. Moreover we have extended the partitioning algorithm by classifying a pseudoknot as either recursive or non-recursive in order to continue with our research …

Pattern Of Use Of Electronic Health Record (Ehr) Among The Chronically Ill: A Health Information National Trend Survey (Hints) Analysis, Rose Calixte, Sumaiya Islam, Zainab Toteh Osakwe, Argelis Rivera, Marlene Camacho-Rivera

Publications and Research

Effective patient–provider communication is a cornerstone of patient-centered care. Patient portals provide an effective method for secure communication between patients or their proxies and their health care providers. With greater acceptability of patient portals in private practices, patients have a unique opportunity to manage their health care needs. However, studies have shown that less than 50% of patients reported accessing the electronic health record (EHR) in a 12-month period. We used HINTS 5 cycle 1 and cycle 2 to assess disparities among US residents 18 and older with any chronic condition regarding the use of EHR for secure direct messaging …

Biol 4010w/7190g/Cisc2810w: Macromolecular Structure And Bioinformatics, Shaneen Singh

Open Educational Resources

No abstract provided.

Biomedical Informatics Colloquium, Bio 4050, Course Outline, Eugenia G. Giannopoulou

Open Educational Resources

A seminar-based course that exposes students to current research topics in the fields of Bioinformatics and Medical Informatics. Weekly presentations by invited speakers and/or faculty introduce students to the broad diversity of research areas in both fields, and engages them in critical thinking and writing. Online lectures and reading activities will be given periodically.

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

Rotavirus A Genome Segments Show Distinct Segregation And Codon Usage Patterns, Irene Hoxie, John J. Dennehy

Publications and Research

Reassortment of the Rotavirus A (RVA) 11-segment dsRNA genome may generate new genome constellations that allow RVA to expand its host range or evade immune responses. Reassortment may also produce phylogenetic incongruities and weakly linked evolutionary histories across the 11 segments, obscuring reassortment-specific epistasis and changes in substitution rates. To determine the co-segregation patterns of RVA segments, we generated time-scaled phylogenetic trees for each of the 11 segments of 789 complete RVA genomes isolated from mammalian hosts and compared the segments’ geodesic distances. We found that segments 4 (VP4) and 9 (VP7) occupied significantly different tree spaces from each other …

Extending Import Detection Algorithms For Concept Import From Two To Three Biomedical Terminologies, Vipina K. Keloth, James Geller, Yan Chen, Julia Xu

Publications and Research

Background: While enrichment of terminologies can be achieved in different ways, filling gaps in the IS-A hierarchy backbone of a terminology appears especially promising. To avoid difficult manual inspection, we started a research program in 2014, investigating terminology densities, where the comparison of terminologies leads to the algorithmic discovery of potentially missing concepts in a target terminology. While candidate concepts have to be approved for import by an expert, the human effort is greatly reduced by algorithmic generation of candidates. In previous studies, a single source terminology was used with one target terminology.

Methods: In this paper, we are extending …

Missing Lateral Relationships In Top‑Level Concepts Of An Ontology, Ling Zheng, Yan Chen, Hua Min, P. Lloyd Hildebrand, Hao Liu, Michael Halper, James Geller, Sherri De Coronado, Yehoshua Perl

Publications and Research

Background: Ontologies house various kinds of domain knowledge in formal structures, primarily in the form of concepts and the associative relationships between them. Ontologies have become integral components of many health information processing environments. Hence, quality assurance of the conceptual content of any ontology is critical. Relationships are foundational to the definition of concepts. Missing relationship errors (i.e., unintended omissions of important definitional relationships) can have a deleterious effect on the quality of an ontology. An abstraction network is a structure that overlays an ontology and provides an alternate, summarization view of its contents. One kind of abstraction network is …

Outlier Concepts Auditing Methodology For A Large Family Of Biomedical Ontologies, Ling Zheng, Hua Min, Yan Chen, Vipina Keloth, James Geller, Yehoshua Perl, George Hripcsak

Publications and Research

Background: Summarization networks are compact summaries of ontologies. The “Big Picture” view offered by summarization networks enables to identify sets of concepts that are more likely to have errors than control concepts. For ontologies that have outgoing lateral relationships, we have developed the "partial-area taxonomy" summarization network. Prior research has identified one kind of outlier concepts, concepts of small partials-areas within partial-area taxonomies. Previously we have shown that the small partial-area technique works successfully for four ontologies (or their hierarchies).

Methods: To improve the Quality Assurance (QA) scalability, a family-based QA framework, where one QA technique is potentially applicable to …

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …

Development Of Ligand Guided Selection (Ligs) To Identify Specific Dna Aptamers Against Cell Surface Proteins, Hasan Ekrem Zumrut

Dissertations, Theses, and Capstone Projects

Oligonucleotide aptamers (nucleic acid-based affinity reagents) are an emerging class of synthetic molecules that display high affinity and specificity towards their targets. Aptamer molecules for a target of interest are obtained using a combinatorial chemistry-based method termed systematic evolution of ligands by exponential enrichment (SELEX). SELEX is an in vitro selection process in which a random oligonucleotide library is subjected to repeated cycles of target incubation, separation, and amplification until target-specific evolved sequences become prevalent in the library. Typically, SELEX is used against target molecules such as small molecules and proteins, in their purified state. However, aptamers selected against purified …

On The Distribution Of Genetic Variation In Ecological Communities, Isaac Overcast

Dissertations, Theses, and Capstone Projects

Biodiversity in ecological communities is structured hierarchically across spatial and temporal scales. Many open questions remain as to how this structure accumulates. For example, what are the relative contributions of dispersal versus in situ speciation? Or, how important are stochastic drift versus deterministic processes? Up to this point, these questions have been investigated by isolated disciplines (e.g. macroecology, comparative phylogeography, macroevolution) using tools and data that tend to focus on only one axis of community scale data (e.g. phylogenies, relative abundances, and/or trait information). Yet we know that there are feedbacks among processes that respond on short, medium, and long …

Designing Computational Biology Workflows With Perl - Part 1, Esma Yildirim

Open Educational Resources

This material introduces Linux File System structures and demonstrates how to use commands to communicate with the operating system through a Terminal program. Basic program structures and system() function of Perl are discussed. A brief introduction to gene-sequencing terminology and file formats are given.

Designing Computational Biology Workflows With Perl - Part 1, Esma Yildirim

Open Educational Resources

This material introduces the AWS console interface, describes how to create an instance on AWS with the VMI provided, connect to that machine instance using the SSH protocol. Once connected, it requires the students to write a script to enter the data folder, which includes gene-sequencing input files and print the first five line of each file remotely. The same exercise can be applied if the VMI is installed on a local machine using virtualization software (e.g. Oracle VirtualBox). In this case, the Terminal program of the VMI can be used to do the exercise.

Designing Computational Biology Workflows With Perl - Part 2, Esma Yildirim

Open Educational Resources

This material introduces the AWS console interface, describes how to create an instance on AWS with the VMI provided and connect to that machine instance using the SSH protocol. Once connected, it requires the students to write a script to automate the tasks to create VCF files from two different sample genomes belonging to E.coli microorganisms by using the FASTA and FASTQ files in the input folder of the virtual machine. The same exercise can be applied if the VMI is installed on a local machine using virtualization software (e.g. Oracle VirtualBox). In this case, the Terminal program of the …

Designing Computational Biology Workflows With Perl - Part 2, Esma Yildirim

Open Educational Resources

This material briefly reintroduces the DNA double Helix structure, explains SNP and INDEL mutations in genes and describes FASTA, FASTQ, BAM and VCF file formats. It also explains the index creation, alignment, sorting, marking duplicates and variant calling steps of a simple preprocessing workflow and how to write a Perl script to automate the execution of these steps on a Virtual Machine Image.

Bioinformatics Ii, Bio 3352, Course Outline, Eugenia G. Giannopoulou

Open Educational Resources

This course is a continuation of Bioinformatics I. Topics include gene expression, microarrays, next- generation sequencing methods, RNA-seq, large genomic projects, protein structure and stability, protein folding, and computational structure prediction of proteins; proteomics; and protein-nucleic acid interactions. The lab component includes R-based statistical data analysis on large datasets, introduction to big data analysis tools, protein visualization software, internet-based tools and high-level programming languages.

Designing Computational Biology Workflows With Perl - Part 1 & 2, Esma Yildirim

Open Educational Resources

This manual guides the instructor to combine the partial files of the virtual machine image and construct sequencer.ova file. It is accompanied by the partial files of the virtual machine image.

Evolution Of Endurance Running Genes Across Primates, Natalia T. Grube

Theses and Dissertations

The endurance running hypothesis has emerged as a key idea to explain several unique anatomical, physiological, and genetic features of modern humans—among these features is the evolution of ACTN3 (Bramble & Lieberman 2004, Nature), a gene linked to human athletic performance. An additional gene linked to human endurance performance is ACE. Because endurance running is a uniquely human trait, I predicted that ACE and ACTN3 genes would be evolving adaptively in the human lineage when examined in a wider primatological framework. To test this I compiled ACE and ACTN3 genes from 14 primate species and phylogenetically tested if these genes …