Bioinformatics Commons^™

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 …

The Deleterious F109s Mutation Disrupts Binding Of Sex-Determining Region Y With Dna, Mohammed Baqur S. Al-Shuhaib Mbsa

Karbala International Journal of Modern Science

Sex-determining region Y (SRY) protein is the master switch in the initiation of male sex differentiation. Mutation in SRY gene results in ambiguous genitalia and abnormalities in reproductive organs. Its function is mainly controlled by its high mobility group (HMG) box. Damage to the HMG box may cause dysfunction of the SRY protein, which may, in turn, lead to sex reversal. This study was conducted to prioritize the deleterious effects of the non-synonymous single nucleotide polymorphisms (nsSNPs) on SRY protein. A series of computational tools were applied to predict nsSNPs with the most harmful effects on protein structure, function, and …

Molecular Identification, Antioxidant Efficacy Of Phenolic Compounds, And Antimicrobial Activity Of Beta-Carotene Isolated From Fruiting Bodies Of Suillus Sp, Shimal Yonuis Abdulhadi, Raghad Nawaf Gergees, Ghazwan Qasim Hasan

Karbala International Journal of Modern Science

Suillus species, in general, are edible mushrooms, and environmentally important that are associated mostly with pine trees in the tropics regions. These fungi considered a remarkable source of phenolic compounds that play a crucial role as antioxidants which may reduce the risk of most human chronic diseases such as cancer, diabetes, asthma, atherosclerosis, Alzheimer, and others. On the other hand, carotenoids (β carotene) are the most popular natural pigments which play an important role to protect the plants from photo-oxidative reactions. In human, these compounds prevent oxidative stress and expects to have antimicrobial activity. Here, the phenolic compounds were …

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

Biochemistry Publications

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi‐gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support vector machine (SVM) learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology‐based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway‐extended SVMs predicted responses in …

Probing Structure, Function And Dynamics In Bacterial Primary And Secondary Transporter-Associated Binding Proteins, Shantanu Shukla

Doctoral Dissertations

Substrate binding proteins (SBPs) are ubiquitous in all life forms and have evolved to perform diverse physiological functions, such as in membrane transport, gene regulation, neurotransmission, and quorum sensing. It is quite astounding to observe such functional diversity among the SBPs even when they are restricted by their fold space. Therefore, the SBPs are an excellent set of proteins that can reveal how proteins evolution novel function in a structurally conserved/constrained fold. This study attempts to understand the phenomenon of affinity and specificity evolution in SBPs by combining a set of biochemical, biophysical, and structural studies on the SBPs involved …

Development Of Computational Tools To Target Microrna, Luo Song

Dissertations & Theses (Open Access)

MicroRNAs (a.k.a, miRNAs) play an important role in disease development. However, few of their structures have been determined and structure-based computational methods remain challenging in accurately predicting their interactions with small molecules. To address this issue, my thesis is to develop integrated approaches to screening for novel inhibitors by targeting specific structure motifs in miRNAs. The project starts with implementing a tool to find potential miRNA targets with desired motifs. I combined both sequence information of miRNAs and known RNA structure data from Protein Data Bank (PDB) to predict the miRNA structure and identify the motif to target, then I …

The Effect Of Nuclear Perturbations On The 3d Organization Of The Genome, Rosela Golloshi

Doctoral Dissertations

Cells in our body experience constant mechanical forces that influence biological functions such as growth and development. The nucleus has been implicated as a key mechanosensor and can directly influence chromatin organization and epigenetic alterations leading to gene expression changes. However, the mechanism by which such mechanical forces lead to genomic alterations and expression of mechanosensitive genes is not fully understood. The work presented in this dissertation investigates the effect of mechanical and epigenetic perturbations on the 3D genome organization. To investigate this 3D genome folding, we use Chromosome Conformation Capture followed by high throughput sequencing (Hi-C) (Chapter-1) which identifies …

Structure–Activity Relationship-Based Chemical Classification Of Highly Imbalanced Tox21 Datasets, Gabriel Idakwo, Sundar Thangapandian, Joseph Luttrell, Yan Li, Nan Wang, Zhaoxian Zhou, Huixiao Hong, Bei Yang, Chaoyang Zhang, Ping Gong

Faculty Publications

The specificity of toxicant-target biomolecule interactions lends to the very imbalanced nature of many toxicity datasets, causing poor performance in Structure–Activity Relationship (SAR)-based chemical classification. Undersampling and oversampling are representative techniques for handling such an imbalance challenge. However, removing inactive chemical compound instances from the majority class using an undersampling technique can result in information loss, whereas increasing active toxicant instances in the minority class by interpolation tends to introduce artificial minority instances that often cross into the majority class space, giving rise to class overlapping and a higher false prediction rate. In this study, in order to improve the …

Observed Defects Of Swiss Cheese Based On The Microbiome Contribution To The Production Of Organic Acids, Vannessa D. Campfield

Boise State University Theses and Dissertations

The United States Department of Agriculture downgrades on the order of 17% of all Swiss cheese produced in the United States due to defects. Many of these defects are related to improper eye formation, number, distribution, or size; leading to an industry loss of over $69 million per annum. The microbiome in Swiss-type cheeses plays a significant role in eye development due to production of organic acids and gaseous emissions contingent on bacterial abundance and phenotype. The relationship between bacteria and the organic acids they produce leading to Swiss cheese defects can be correlated using Next-generation sequencing and high-performance liquid …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Gene Set Testing By Distance Correlation, Sho-Hsien Su

Graduate Theses and Dissertations

Pathways are the functional building blocks of complex diseases such as cancers. Pathway-level studies may provide insights on some important biological processes. Gene set test is an important tool to study the differential expression of a gene set between two groups, e.g., cancer vs normal. The differential expression of a gene set could be due to the difference in mean, variability, or both. However, most existing gene set tests only target the mean difference but overlook other types of differential expression. In this thesis, we propose to use the recently developed distance correlation for gene set testing. To assess the …

Modified-Half-Normal Distribution And Different Methods To Estimate Average Treatment Effect., Jingchao Sun

Electronic Theses and Dissertations

This dissertation consists of three projects related to Modified-Half-Normal distribution and causal inference. In my first project, a new distribution called Modified-Half-Normal distribution was introduced. I explored a few of its distributional properties, the procedures for generating random samples based on Bayesian approaches, and the parameter estimation based on the method of moments. The second project deals with the problem of selection bias of average treatment effect (ATE) if we use the observational data. I combined the propensity score based inverse probability of treatment weighting (IPTW) method and the directed acyclic graph (DAG) to solve this problem. The third project …

A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very poor patient prognosis (5-year survival of ≤ 7%). While transcriptional profiling has aided in the classification of this disease into at least two broader subtypes, this alone has so far been insufficient to inform on more nuanced patterns of oncogenic dependency. We hypothesized that a more comprehensive and granular characterization of PDAC disease diversity is required to establish relevant context for targeted therapy. To this end, we sought to establish an integrated platform to: i) more comprehensively characterize differential oncogenic signaling across our tumor models, and ii) establish …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations & Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

Investigation Of Sulfur Cycling In Marine Sponge Cinachyrella Spp. From A South Florida Reef, Shelby K. Cain

All HCAS Student Capstones, Theses, and Dissertations

Symbionts within marine sponges are actively participating in the biogeochemical cycles. Among them, the role of symbiont microbes in the sulfur cycle remains a mystery. This study measured the abundance of microbes within the genus Cinachyrella before and after exposure to hydrogen sulfide. A four-part study was conducted: a) five-hour drop experiments, b) vertical distribution experiments, c) five-hour uptake experiments, and d) long-term exposure experiments. The five-hour drop experiment utilized a microsensor to measure sulfide levels, which was lowered 1.0 mm every thirty minutes for a total of 5 hours. Three trials were performed, each with one sponge and a …

Decoding The Evolutionary Response To Prostate Cancer Therapy Using Plasma Genome Sequencing, Naveen Ramesh

Dissertations & Theses (Open Access)

Investigating genome evolution in response to therapy is difficult in human tissue samples due to the difficulty in accessing metastatic tumor sites and logistical challenges of collecting longitudinal samples. To overcome these issues, we developed an unbiased whole-genome plasma DNA sequencing approach called PEGASUS that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach was applied to study longitudinal blood plasma samples from prostate cancer patients. A molecular characterization of archival plasma DNA from 233 patients and genomic profiling of 101 patients identified clinical correlations of aneuploid plasma DNA profiles with poor survival, increased …

Carbon Metabolism In Cave Subaerial Biofilms, Victoria E. Frazier

Masters Theses

Subaerial biofilms (SABs) grow at the interface between the atmosphere and rock surfaces in terrestrial and subterranean environments around the world. Multi-colored SABs colonizing relatively dry and nutrient-limited cave surfaces are known to contain microbes putatively involved in chemolithoautotrophic processes using inorganic carbon like carbon dioxide (CO₂) or methane (CH₄). However, the importance of CO₂ and CH₄ to SAB biomass production has not been quantified, the environmental conditions influencing biomass production and diversity have not been thoroughly evaluated, and stable carbon and nitrogen isotope compositions have yet to be determined from epigenic cave SABs. …

Genomics Education Partnership F Element Annotation Report, Amanda Moy

Honors Projects

The Genomics Education Partnership (GEP), headquartered at the University of Alabama, is a collection of over 100 universities that provide training and resources in order to provide students experiential learning in bioinformatics and genomics. The GEP hosts numerous research projects, including the F element project. The F element project has the main focus of annotating the F element genes of the fruit fly species D. ananassae, D. bipectinata, D. kikkawai, and D. takahashii. The Muller F element is the smallest chromosome in Drosophila species. However, the four species listed above have a notably larger F element than other …