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Interpretable And Data-Driven Machine Learning Models For Analyzing High-Dimensional Biological Data, Junchen Yang

Yale Graduate School of Arts and Sciences Dissertations

High-dimensional biological data, including single-cell omics, are prevalent in modern biology for characterizing a wide range of biological processes and phenomena. Although our capacity to generate such data has expanded at an unprecedented pace, significant challenges remain in extracting the informative features and the underlying biological signals. In particular, these datasets not only exhibit high dimensionality but also suffer from issues including inherent noise, low signal-to-noise ratio, and intrinsic heterogeneity. While machine learning models hold great promise for analyzing such data, their complexity and sensitivity to data characteristics often impede biological interpretability. To address these interconnected challenges, this thesis develops …

Engaging Students In A Genetics Course-Based Undergraduate Research Experience Utilizing Caenorhabditis Elegans In Hybrid Learning To Explore Human Disease Gene Variants, Natalie Forte, Virginia Veasey, Bethany Christie, Amira Carter, Marli Hanks, Alan Holderfield, Taylor Houston, Anil Challa, Ashley Turner

Research, Publications & Creative Work

Genetic analysis in model systems using bioinformatic approaches provides a rich context for a concrete and conceptual understanding of gene structure and function. With the intent to engage students in research and explore disease biology utilizing the nematode Caenorhabditis elegans model, we developed a semester-long course-based undergraduate research experience (CURE) in a hybrid (online/in-person) learning environment—the gene-editing and evolutionary nematode exploration CURE (GENE-CURE). Using a combination of bioinformatic and molecular genetic tools, students performed structure-function analysis of disease-associated variants of uncertain significance (VUS) in human orthologs. With the aid of a series of workshop-style research sessions, students worked in teams …

Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic

Dissertations and Theses (Open Access)

The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called essential genes and provide insights into disease-specific candidate therapeutic targets. Additionally, CRISPR offers other applications for genome editing. Two applications this dissertation is based on are 1) combination of gene knockout and drug treatment, which enables the identification of chemogenetic interactions, or gene mutations that enhance or suppress the activity of a drug, and 2) combinatorial editing, …

Modeling And Analysis Of Subcellular Protein Localization In Hyper-Dimensional Fluorescent Microscopy Images Using Deep Learning Methods, Yang Jiao

UNLV Theses, Dissertations, Professional Papers, and Capstones

Hyper-dimensional images are informative and become increasingly common in biomedical research. However, the machine learning methods of studying and processing the hyper-dimensional images are underdeveloped. Most of the methods only model the mapping functions between input and output by focusing on the spatial relationship, whereas neglect the temporal and causal relationships. In many cases, the spatial, temporal, and causal relationships are correlated and become a relationship complex. Therefore, only modeling the spatial relationship may result in inaccurate mapping function modeling and lead to undesired output. Despite the importance, there are multiple challenges on modeling the relationship complex, including the model …

Targeting The Side-Chain Convergence Of Α-Helical Hot Spots To Design Small-Molecule Mimetics Disrupting Protein-Protein Interaction, Zhen Wang

USF Tampa Graduate Theses and Dissertations

α-Helix accounts for the largest class of protein secondary structures and plays a key role in mediating protein-protein interactions (PPIs). Small-molecule α-helix mimetics mimic the structural features of α-helical hot spots and offer a powerful tool to unravel complex signaling networks and mitigate aberrant PPIs. In this dissertation, the side-chain conformational convergence of α-helical hot spots was disclosed, and insights into the side-chain convergence were exploited to instruct the design of small-molecule α-helix mimetics. The first chapter of this dissertation provides an overview of the characteristics of α-helical hot spots and current strategies to design small-molecule α-helix mimetics. In chapter …

Interdisciplinary Stem Undergraduate Programs And The Effectiveness Of Computing Competencies Within The Curriculum, Katherine G. Herbert, Thomas J. Marlowe, Kees Leune, Robert M. Siegfried, Jeanette Wilmanski

Department of Computer Science Faculty Scholarship and Creative Works

Undergraduate interdisciplinary, multidisciplinary and transdisciplinary computing-related STEM programs are proliferating extensively. Each of these programs requires a robust computing component to be integrated into the curriculum. However, including an introductory, programmingoriented sequence designed for CS majors is not always the best fit for these multifaceted programs. In this work in progress paper, we set out to investigate possibilities and issues for the computing component, focusing on three fields: bioinformatics, data science, and cybersecurity. We explore commonalities and differences, and discuss initial plans to test our hypotheses. In doing so, we consider data organization, data acquisition, and a preliminary survey design.

Development Of Computational To Ols To Target Microrna, Luo Song

Dissertations and 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 …

Methods To Integrate Genetic And Clinical Data For Disease Subtyping, Diana Mabel Diaz-Herrera

Wayne State University Dissertations

Enormous efforts have been made to collect genetic and clinical data from cancer patients to advance the understanding of disease development and progression. Processing and analyzing these flows of data is challenging. Many computational methods have been proposed to help different fronts of biology and medicine. The integration of clinical and genetic data using computational methods towards personalized medicine is considered the future for oncology studies, and this thesis contributes in this direction. This thesis presents three new data integration approaches to elucidate granular and meaningful disease sub-types from high-dimensional complex genetic and clinical variables, which is an essential step …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

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 …

Of Donuts And Promo : In Silico Approaches To Identification Of Transcriptional Regulators Of Salivary Acinar Differentiation, Connor Cillian Duffy

Legacy Theses & Dissertations (2009 - 2024)

The salivary gland is an organ often taken for granted by most people. However, its proper function is essential for several everyday activities, such as speaking, swallowing, and tasting. As such, impaired salivary gland function, such as that caused by Sjögren’s Syndrome or radiotherapy for head and neck cancers, can lead to a significantly reduced quality of life. The cells that produce saliva in salivary glands are known as acinar cells, which arise from proacinar cells generated during embryonic development. As such, in studying the promoter regions of proacinar and acinar genes, it may be possible to identify common transcription …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Gesture: An Online Hand-Drawing Tool For Gene Expression Pattern Search, Chunyan Wang, Yiqing Xu, Xuelin Wang, Li Zhang, Suyun Wei, Qiaolin Ye, Youxiang Zhu, Hengfu Yin, Manoj Nainwal, Luis Tanon-Reyes, Feng Cheng, Tongming Yin, Ning Ye

Molecular Biosciences Faculty Publications

Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene expression data is not an easy task. Clustering, a popular method, is often used to classify similar expression genes, however, genes with a ‘desirable’ or ‘user-defined’ pattern cannot be efficiently detected by clustering methods. To address these limitations, we developed an online tool called GEsture. Users can draw, or graph a curve using a mouse instead of inputting abstract parameters of clustering methods. GEsture explores genes showing similar, opposite and time-delay expression patterns with …

A Cure For Salmonella: Engaging Students In Pathogen Microbiology And Bioinformatics, Sophie Jurgensen

Senior Honors Projects, 2010-2019

Advances in Next Generation Sequencing (NGS) technology have generated a vast amount of publicly available genomic data, creating a need for students with training in computational analysis. This laboratory lesson is a course-based undergraduate research experience (CURE) focusing on environmental Salmonella, a common foodborne pathogen that is of great interest to public health laboratories but is relatively less virulent than most other such pathogens. As discovery is a central tenet of CUREs, students isolate novel Salmonella enterica and related strains from stream sediment, poultry litter, or other sources in the first half of the lesson (Module 1). They also …

Integrative Pathway Analysis Pipeline For Mirna And Mrna Data, Diana Mabel Diaz Herrera

Wayne State University Theses

The identification of pathways that are involved in a particular phenotype helps us understand the underlying biological processes. Traditional pathway analysis techniques aim to infer the impact on individual pathways using only mRNA levels. However, recent studies showed that gene expression alone is unable to capture the whole picture of biological phenomena. At the same time, MicroRNAs (miRNAs) are newly discovered gene regulators that have shown to play an important role in diagnosis, and prognosis for different types of diseases. Current pathway analysis techniques do not take miRNAs into consideration. In this project, we investigate the effect of integrating miRNA …

The Influences Of Different Socioeconomic Scenarios In Bioinformatics And Biotechnology Research: The Ethical Issues Arising From Technological Advances, Marcia Miki Sato

Theses

In the last couple decades, we could see the combination of technology and biology taking large steps in science. As new fields, bioinformatics and biotechnology also led to important discussions between excited scientists and social thinkers. The divergent opinions argue about the amazing possibilities of human advances and the social issues that follow the progress. This paper discusses ethical matters of new developments and compares policy choices with respect to research and use of biotechnology and bioinformatics in different countries. Even though the world is increasingly globalized, the comparisons suggest that different cultures have different ethical responses and public policies …

Killing Two Birds With One Stone: The Concurrent Development Of The Novel Alignment Free Tree Building Method, Scrawkov-Phy, And The Extensible Phyloinformatics Utility, Emu-Phy., J. Nick Fisk

Theses

Many components of phylogenetic inference belong to the most computationally challenging and complex domain of problems. To further escalate the challenge, the genomics revolution has exponentially increased the amount of data available for analysis. This, combined with the foundational nature of phylogenetic analysis, has prompted the development of novel methods for managing and analyzing phylogenomic data, as well as improving or intelligently utilizing current ones. In this study, a novel alignment tree building algorithm using Quasi-Hidden Markov Models (QHMMs), Scrawkov-Phy, is introduced. Additionally, exploratory work in the design and implementation of an extensible phyloinformatics tool, EMU-Phy, is described. Lastly, features …

Novel Dynamic Partial Reconfiguration Implementations Of The Support Vector Machine Classifier On Fpga, Hanaa Hussain, Khaled Benkrid, Hüseyi̇n Şeker

Turkish Journal of Electrical Engineering and Computer Sciences

The support vector machine (SVM) is one of the highly powerful classifiers that have been shown to be capable of dealing with high-dimensional data. However, its complexity increases requirements of computational power. Recent technologies including the postgenome data of high-dimensional nature add further complexity to the construction of SVM classifiers. In order to overcome this problem, hardware implementations of the SVM classifier have been proposed to benefit from parallelism to accelerate the SVM. On the other hand, those implementations offer limited flexibility in terms of changing parameters and require the reconfiguration of the whole device. The latter interrupts the operation …

A Reproducible Approach To High-Throughput Biological Data Acquisition And Integration, Daniela Börnigen, Yo Sup Moon, Gholamali Rahnavard, Levi Waldron, Lauren Mciver, Afrah Shafquat, Eric A. Franzosa, Larissa Miropolsky, Christopher Sweeney, Xochitl C. Morgan, Wendy S. Garrett, Curtis Huttenhower

Publications and Research

Modern biological research requires rapid, complex, and reproducible integration of multiple experimental results generated both internally and externally (e.g., from public repositories). Although large systematic meta-analyses are among the most effective approaches both for clinical biomarker discovery and for computational inference of biomolecular mechanisms, identifying, acquiring, and integrating relevant experimental results from multiple sources for a given study can be time-consuming and error-prone. To enable efficient and reproducible integration of diverse experimental results, we developed a novel approach for standardized acquisition and analysis of high-throughput and heterogeneous biological data. This allowed, first, novel biomolecular network reconstruction in human prostate cancer, …

Gene Ontology Analysis Of Pairwise Genetic Associations In Two Genome-Wide Studies Of Sporadic Als, Nora Chung Kim, Peter C. Andrews, Folkert W. Asselbergs, H Robert Frost, Scott M. Williams, Brent T. Harris, Cynthia Read, Kathleen D. Askland, Jason H. Moore

Dartmouth Scholarship

It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO).

Genotyping On Custom Arrays Using A Parallel Data Pipeline, Brian Albere

Master's Theses and Capstones

In the past, genotyping (determining a set of alleles in an organism) has been an extremely challenging process. The time, monetary, and technology demands of the task have limited genotype data to a small variety of scientific model organisms with the capacity to conduct genetic crosses. New sequencing technology from companies such as NimbleGen, however, can generate custom organism-specific microarrays at relatively low cost. The combination of these arrays and the knowledge of species' genome-wide SNPs allow genotype experiments, such as generation maps, QTL studies, and natural population variation studies, to be conducted on virtually any organism. Although the NimbleGen …

Algorithmic Techniques Employed In The Isolation Of Codon Usage Biases In Prokaryotic Genomes, Douglas W. Raiford Iii

Browse all Theses and Dissertations

While genomic sequencing projects are an abundant source of information for biological studies ranging from the molecular to the ecological in scale, much of the information present may yet be hidden from casual analysis. One such information domain, trends in codon usage, can provide a wealth of information about an organism's genes and their expression. Degeneracy in the genetic code allows more than one triplet codon to code for the same amino acid, and usage of these codons is often biased such that one or more of these synonymous codons is preferred. Isolation of translational efficiency bias can have important …

Bioinformatic Study Of Gamma-Secretase And Its Substrates, Fei Nan

Graduate Theses, Dissertations, and Problem Reports (ETD)

gamma-Secretase is an enzymatic complex critical to amyloid formation and other important pathophysiological processes. Non-specific gamma-secretase inhibitors are not ideal for intervention of familial Alzheimer's disease. The four essential include Presenilin (PS1 or PS-2), APH-1, Pen-2, nicastrin (Nct). Also gamma-secretase cleaves a variety of substrates (over 30). But different sites are cleaved even in a single substrate and no consensus sequence for cleavage by gamma-secretase is identified. We hypothesize that consensus compositional sequence (or functional domain) in components of gamma-secretase and/or its substrates should exist during gamma-secretase regulation and specific gamma-secretase inhibitor based on such consensus sequence (or functional domain) …

Bioconductor: Open Software Development For Computational Biology And Bioinformatics, Robert C. Gentleman, Vincent J. Carey, Douglas J. Bates, Benjamin M. Bolstad, Marcel Dettling, Sandrine Dudoit, Byron Ellis, Laurent Gautier, Yongchao Ge, Jeff Gentry, Kurt Hornik, Torsten Hothorn, Wolfgang Huber, Stefano Iacus, Rafael Irizarry, Friedrich Leisch, Cheng Li, Martin Maechler, Anthony J. Rossini, Guenther Sawitzki, Colin Smith, Gordon K. Smyth, Luke Tierney, Yee Hwa Yang, Jianhua Zhang

Bioconductor Project Working Papers

The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. We detail some of the design decisions, software paradigms and operational strategies that have allowed a small number of researchers to provide a wide variety of innovative, extensible, software solutions in a relatively short time. The use of an object oriented programming paradigm, the adoption and development of a software package system, designing by contract, distributed development and collaboration with other projects are elements of this project's success. Individually, each of these concepts are useful and important but when combined they have …

Binary Representation Of Dna Sequences Towards Developing Useful Algorithms In Bioinformatic Data-Mining, Shivani. Pandya

Electronic Theses and Dissertations 2000 - 2009

This thesis refers to a research addressing the use of binary representation of the DNA for the purpose of developing useful algorithms for Bioinformatics. Pertinent studies address the use of a binary form of the DNA base chemicals in information-theoretic base so as to identify symmetry between DNA and complementary DNA. This study also refers to "fuzzy" (codon-noncodon) considerations in delinating codon and noncodon regimes in a DNA sequences. The research envisaged further includes a comparative analysis of the test results on the aforesaid efforts using different statistical metrics such as Hamming distance Kullback-Leibler measure etc. the observed details supports …