Computational Biology Commons^™

Reconstructing Mutational Lineages In Breast Cancer By Multi-Patient-Targeted Single Cell Dna Sequencing, Jake Leighton

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high rates of metastasis and recurrence, where TNBC patients have a poor 5-year survival and ~50% are non-responsive to chemotherapy. Aneuploidy is a cancer hallmark that is pervasive in over 90% of breast cancer patients and is indicative of complex genomic rearrangements that are acquired during tumor initiation. Although copy number aberrations have been extensively studied in relation to aneuploidy and TNBC initiation, little is currently known regarding the timing and impact of single nucleotide variants (SNVs) contributing to these early transformative genomic events. Paramount to novel …

Identifying Non-Traditional Slippery Sequences Associated With Translational Frameshifts, Aaron J. Gin, Kari Lynn Clase

Graduate Industrial Research Symposium

Genetic frameshifts are a mutation in which
a nucleotide skip leads to a shift in the
reading frame. In viruses, these frameshifts
can be programmed using a slippery
sequence to bypass the stop codon
associated with the initial protein. This
allows for variable control of protein
expression. In bacteriophages, translational
frameshifts have been identified but only a
few have been proven experimentally. Using
experimental data and comparative
genomics, non-traditional slippery
sequences can be identified as assisting in
controlling the protein coding throughout
viruses. Novel slippery sequences can aid in
the understanding of protein expression in
biological environments and further the …

Selection Pressure On Surface Exposed Virus Proteins, Sareh Bagherichimeh

Electronic Thesis and Dissertation Repository

Viral infection requires the interaction between virus surface-exposed (SE) proteins and host cell receptors. This can result in an “arms race” that is assumed to drive accelerated rates of evolution, and some well known examples of diversifying selection involve surface pro- teins (HIV-1 env, influenza hemagglutinin). We conducted a systematic analysis to determine whether this is truly a distinctive feature of SE virus proteins, in comparison to non-SE proteins encoded by the same genomes.

We obtained reference and all neighbour genomes of 52 human viruses from the NCBI Viral Genomes database. The coding sequences (CDS) of each genome extracted by …

Caribbean Reef-Building Coral-Symbiodiniaceae Network: Identifying Symbioses Critical For System Stability In A Changing Climate, Shaman Patel

All HCAS Student Capstones, Theses, and Dissertations

Increasing global ocean temperatures and frequency of marine heatwaves pose dire consequences for coral reefs. High temperatures often lead to disruptions in coral symbiosis resulting in coral bleaching, increasing the mortality of corals. However, corals can potentially avoid bleaching peril by associating with thermally tolerant symbionts. Here we provide a tool for understanding symbiosis network stability of Caribbean reef-building corals. We created a network of Caribbean hermatypic corals and their associated Symbiodiniaceae phylotypes. A bleaching model was applied to this network to test for resilience and robustness (R50) to thermal stress. It was also layered with trait data for coral …

Deciphering The Genetic Architecture Of Key Female Floral Traits For Hybrid Wheat Seed Production, Juan Jimenez

Theses, Dissertations, and Student Research in Agronomy and Horticulture

Wheat (Triticum aestivum L.) is a staple cereal that provides 20% of the calories and proteins in human intake (Ray et al., 2013). Global population is projected to increase to 9.7 billion by 2050. Food production must increase by 70% to feed this future population. Wheat production is in crisis due to political and environmental challenges and is projected to decline by 0.8% in 2022 (FAO, 2022). To ensure food security yield genetic gain must increase by around 1.4% annually. Taking advantage of heterosis, hybrid wheat has the potential to boost grain yield. However, hybrid wheat seed production systems …

Large Genomes Assembly Using Mapreduce Framework, Yuehua Zhang

All Dissertations

Knowing the genome sequence of an organism is the essential step toward understanding its genomic and genetic characteristics. Currently, whole genome shotgun (WGS) sequencing is the most widely used genome sequencing technique to determine the entire DNA sequence of an organism. Recent advances in next-generation sequencing (NGS) techniques have enabled biologists to generate large DNA sequences in a high-throughput and low-cost way. However, the assembly of NGS reads faces significant challenges due to short reads and an enormously high volume of data. Despite recent progress in genome assembly, current NGS assemblers cannot generate high-quality results or efficiently handle large genomes …

Sequence-Based Bioinformatics Approaches To Predict Virus-Host Relationships In Archaea And Eukaryotes, Yingshan Li

Computer Science and Engineering: Theses, Dissertations, and Student Research

Viral metagenomics is independent of lab culturing and capable of investigating viromes of virtually any given environmental niches. While numerous sequences of viral genomes have been assembled from metagenomic studies over the past years, the natural hosts for the majority of these viral contigs have not been determined. Different computational approaches have been developed to predict hosts of bacteria phages. Nevertheless, little progress has been made in the virus-host prediction, especially for viruses that infect eukaryotes and archaea. In this study, by analyzing all documented viruses with known eukaryotic and archaeal hosts, we assessed the predictive power of four computational …

Model-Free Identification Of Relevant Variables From Response Data, Alan Veliz-Cuba, David Murrugarra

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Changes In Gene Expression From Long-Term Warming Revealed Using Metatranscriptome Mapping To Fac-Sorted Bacteria, Christopher A. Colvin

Masters Theses

Soil microbiomes play pivotal roles to the health of the environment by maintaining metabolic cycles. One question is how will climate change affect soil bacteria over time and what could the repercussions be. To answer these questions, the Harvard Forest Long-Term Warming Experiment was established to mimic predicted climate change by warming plots of land 5℃ above ambient conditions. In 2017, 14 soil core samples were collected from Barre Woods warming experiment to mark 15 years since the establishment of the soil warming in that location. These samples underwent traditional metatranscriptomics to generate an mRNA library as well as a …

Radiation Exposure Determination In A Secure, Cloud-Based Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Towards More Complete Metagenomic Analyses Through Circularized Genomes And Conjugative Elements, Benjamin R. Joris

Electronic Thesis and Dissertation Repository

Advancements in sequencing technologies have revolutionized biological sciences and led to the emergence of a number of fields of research. One such field of research is metagenomics, which is the study of the genomic content of complex communities of bacteria. The goal of this thesis was to contribute computational methodology that can maximize the data generated in these studies and to apply these protocols human and environmental metagenomic samples.

Standard metagenomic analyses include a step for binning of assembled contigs, which has previously been shown to exclude mobile genetic elements, and I demonstrated that this phenomenon extends to all conjugative …

Identification And Characterization Of Genetic Elements That Regulate A C-Di-Gmp Mediated Multicellular Trait In Pseudomonas Fluorescens, Collin Kessler

Electronic Theses and Dissertations

Microbial communities contain densely packed cells where competition for space and resources are fierce. These communities are generally referred to as biofilms and provide advantages to individual cells against immunological and antimicrobial intervention, dehydration, and predation. High intracellular pools of cyclic diguanylate monophosphate (c-di-GMP) cause cells to aggregate during biofilm formation through the production of diverse extracellular polymers. Genes that encode c-di-GMP catalytic enzymes are commonly mutated during chronic infections where opportunists display enhanced resistance to phagocytosis and antibiotics. Our lab uses an emergent multicellular trait in the model organism Pseudomonas fluorescens Pf0-1 to study the emergence of c-di-GMP mutations …

Methods And Tools To Improve Performance Of Plant Genome Analysis, Drew Ferrell

Theses and Dissertations

Multi -omics data analysis and integration facilitates hypothesis building toward an understanding of genes and pathway responses driven by environments. Methods designed to estimate and analyze gene expression, with regard to treatments or conditions, can be leveraged to understand gene-level responses in the cell. However, genes often interact and signal within larger structures such as pathways and networks. Complex studies guided toward describing dynamic genetic pathways and networks require algorithms or methods designed for inference based on gene interactions and related topologies. Classes of algorithms and methods may be integrated into generalized workflows for comparative genomics studies, as multi -omics …

A Genomic Investigation Of Divergence Between Tuna Species, Pavel V. Dimens

Dissertations

Effective management and conservation of marine pelagic fishes is heavily dependent on a robust understanding of their population structure, their evolutionary history, and the delineation of appropriate management units. The Yellowfin tuna (Thunnus albacares) and the Blackfin tuna (Thunnus atlanticus) are two exploited epipelagic marine species with overlapping ranges in the tropical and sub-tropical Atlantic Ocean. This work analyzed genome-wide genetic variation of both species in the Atlantic basin to investigate the occurrence of population subdivision and adaptive variation. A de novo assembly of the Blackfin tuna genome was generated using Illumina paired-end sequencing data and …

Genome Evolution In The Salicaceae: Genetic Novelty, Horizontal Gene Transfer, And Comparative Genomics, Timothy Yates

Doctoral Dissertations

Genome evolution is a powerful force which shapes genomes over time through processes like mutation, horizontal transfer, and sexual reproduction. Although questions which aim to explore genome evolution are broad, they are all understood through the discovery and comparison of genetic variation. For example, genetic diversity may explain differences in phenotypes, etiology of disease, and is essential for phylogenomic analysis. Recently, the democratization of next generation and third generation DNA sequencing technologies have allowed for genomics to produce large amounts of sequence data. This has facilitated the capture of genetic variation at species and population scales.

Populus and Salix are …

What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu

Doctoral Dissertations

Over the past decade, single-cell technologies evolved from profiling hundreds of cells to millions of cells, and emerged from a single modality of data to cover multiple views at single-cell resolution, including genome, epigenome, transcriptome, and so on. With advance of these single-cell technologies, the booming of multimodal single-cell data creates a valuable resource for us to understand cellular heterogeneity and molecular mechanism at a comprehensive level. However, the large-scale multimodal single-cell data also presents a huge computational challenge for insightful integrative analysis. Here, I will lay out problems in data integration that single-cell research community is interested in and …

Decoding Copy Number Substructure And Evolution From Single Cell Genomics, Darlan Conterno Minussi

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Aneuploidy is a prominent feature in Triple-Negative Breast Cancers (TNBC), however, the evolution of genotypes during tumor expansion remains poorly understood. The prevalent model of TNBC evolution is the Punctuated Copy Number Evolution (PCNE), in which tumors undergo a period of elevated genomic instability, acquiring complex genomic rearrangements within a short timeframe followed by clonal stasis. However, these observations rely on limited cell numbers and inherent experimental bias from first-generation single cell technologies. Therefore, the evolutionary trajectory after the punctuated burst remains unknown. To address this question, we sequenced 9,765 cells from 8 primary TNBCs and 6,413 cells from 4 …

Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases, Mahesh Koirala

All Dissertations

Electrostatics plays an essential role in molecular biology. Modeling electrostatics in molecular biology is complicated due to the water phase, mobile ions, and irregularly shaped inhomogeneous biological macromolecules. This dissertation presents the popular DelPhi package that solves PBE and delivers the electrostatic potential distribution of biomolecules. We used the newly developed DelPhiForce steered Molecular Dynamics (DFMD) approach to model the binding of barstar to barnase and demonstrated that the first-principles method could also model the binding. This dissertation also reflects the use of existing computational approaches to model the effects of Single Amino Acid Variations (SAVs) to reveal molecular mechanisms …

Statistical Genetic Discoveries Using Restricted Maximum Likelihood Method, Erika Wu

2022 REYES Proceedings

In statistical genetics, genetic association and genomic prediction become more successful with a highly heritable trait. Identifying highly heritable components of a complex disease can thus advance scientific understanding of the disease and potentially lead to effective prevention and treatments. Using Matlab and existing large-scale genome datasets, we evaluate a restricted maximum likelihood approach to identify highly heritable components of a complex disease as a function of multiple clinical variables.

Mining Of Producer Recorded Data; Using Beef Calf And Cow Live-Weight Data As A Case Study, Shauna Walsh

ORBioM (Open Research BioSciences Meeting)

Animal live-weight contributes to profitability in beef herds and is a key determinant of overall efficiency of the beef sector. The objective was to develop a novel editing criteria for anomaly detection of beef cow and calf live-weight data. Live-weight data from five sources (i.e., professionally-recorded, owned-scales, borrowed-scales, scales hired from a depot, other) were available from the Irish Cattle Breeding Federation.

A number of alternative methods were used for anomaly detection including: generation of within-herd regression estimates, partial correlations between cow and calf live-weight records and mahalanobis distance. Across each method a value was calculated for each herd based …