Computational Biology Commons^™

Soil Microbial Community Composition Of White Oak Mountain, Tennessee, Matthew Gano, Timothy D. Trott

Research in Biology

Abstract - Soil microbial communities are responsible for nutrient cycling in terrestrial ecosystems and have symbiotic and parasitic relationships with the plant community. However, little is known about the factors that determine the soil microbial community composition. In this study we examined how spring wildflower diversity and geographical factors influence the soil microbial community composition of the second growth oak hickory forests of White Oak Mountain in Southeast Tennessee. The characterization of the soil microbial community was completed with 16S/18S/ITS rDNA amplicon sequencing of total DNA extracted from soil samples that were normalized for each sample plot. Here we characterize …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Genomic Basis Of Antifreeze Trait Divergence In Antarctic And Patagonian Toothfish, Shriram Bhat

2023 Midwest Ecology & Evolution Conference

The Dissostichus genus of notothenioid fish contains two giant, iconic sister species, Dissostichus mawsoni (Antarctic toothfish) and Dissostichus eleginoides (Patagonian toothfish), which inhabit thermally distinct environments. D. mawsoni is protected by antifreeze glycoproteins (AFGPs) from freezing in the cold waters of the Southern Ocean, while D. eleginoides lacks detectable antifreeze activity despite its recent divergence. Interestingly, recent evidence suggests the possibility of a third species in the Dissostichus genus, which is currently believed to be a separate population of D. eleginoides closer to the Southern Ocean whose genome has recently been published. Our study focuses on D. eleginoides specimens from …

Cell-Typing And Interaction Analysis Of The Immune Compartment Of The Tumor Microenvironment Using High-Resolution Omics Modalities, Courtney Taylor Schiebout

Dartmouth College Ph.D Dissertations

Single-cell RNA-sequencing (scRNA-seq) has provided a new frontier for the investigation of complex tissues. One ideal candidate for the utilization of this method is the tumor microenvironment (TME). The TME is often host to a complex set of cell populations and behaviors that can be highly influential for cancer inhibition or progression. This is especially true of the immune compartment of the TME: the presence of certain types of immune cells in the TME and their expression profiles can significantly affect cancer prognosis in some cases. By providing individual cell-level gene expression data, scRNA-seq can be highly informative for characterizing …

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 …

The Allele Catalog Tool: A Web-Based Interactive Tool For Allele Discovery And Analysis, Yen On Chan, Nicholas Dietz, Shuai Zeng, Juexin Wang, Sherry Flint-Garcia, M. Nancy Salazar-Vidal, Mária Škrabišová, Kristin Bilyeu, Trupti Joshi

Biomedical Sciences

Background: The advancement of sequencing technologies today has made a plethora of whole-genome re-sequenced (WGRS) data publicly available. However, research utilizing the WGRS data without further configuration is nearly impossible. To solve this problem, our research group has developed an interactive Allele Catalog Tool to enable researchers to explore the coding region allelic variation present in over 1,000 re-sequenced accessions each for soybean, Arabidopsis, and maize.

Results: The Allele Catalog Tool was designed originally with soybean genomic data and resources. The Allele Catalog datasets were generated using our variant calling pipeline (SnakyVC) and the Allele Catalog pipeline (AlleleCatalog). The …

A Computational Analysis Of Hybrid Genome Assembly Strategies, Joseph Walewski

Computer Science Honors Papers

The central dogma of molecular biology states that DNA is transcribed to RNA and then translated into proteins. Since DNA is the starting material for many of biology’s macromolecules, it has been referred to as “nature’s instruction book.” The sum of all DNA in a cell is referred to as the genome, and genome sequencing is how we interpret the DNA.

Due to limitations on currently available technology, it is not possible to retrieve the entire genome in one contiguous set of data. Therefore, genome sequencing is a computer science problem as sequencing “reads” must be stitched together to obtain …

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyang Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background

Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods

Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …

Characterization Of Cell Type-Specific Molecular Heterogeneity In Cancer Using Multi-Omic Approaches, Min Kyung Lee

Dartmouth College Ph.D Dissertations

Tumors are composed of heterogeneous cell types each with its own unique molecular profiles. Recent advances in single cell genomics technologies have begun to increase our understanding of the molecular heterogeneity that exists in tumors with particular focus on gene expression and chromatin accessibility profiles. However, due to limitations in methods for certain sample types and high cost for single cell genomics, bulk tumor molecular profiling has been and remains widely used. In addition, other facets of single cell epigenomic profiling, particularly methylation and hydroxymethylation, remains underexplored. Thus, investigations to understand the cell type specific epigenetic heterogeneity and the cooperation …

Methylation Patterns Across Tissue Type And Time In Peromyscus Leucopus: A Targeted Museum Study, Loryn Smith

Master's Theses or Doctor of Nursing Practice

Museum specimens are a vital data source for many types of studies. One relatively new use includes studying methylation patterns. Methylation patterns are a form of epigenetics or how gene expression changes without alteration of the genetic code. These patterns have been examined in many mammals. However, the focus has previously been on overall epigenetic patterns. Few studies have investigated whether methylation patterns differ across tissue types, time, or preservation method. In this study, I compared methylation patterns in muscle, liver, toe pads, and nasal bones from Peromyscus leucopus (white-footed mouse) museum specimens collected in 2022, 2018, 2014, and 2008 …

Prediction Of Kinase-Substrate Associations Using The Functional Landscape Of Kinases And Phosphorylation Sites, Serhan Yilmaz, Filipa Blasco Tavares Pereira Lopes, Mark R. Chance, Mehmet Koyutürk

Faculty Scholarship

Protein phosphorylation is a key post-translational modification that plays a central role in many cellular processes. With recent advances in biotechnology, thousands of phosphorylated sites can be identified and quantified in a given sample, enabling proteome-wide screening of cellular signaling. However, for most (> 90%) of the phosphorylation sites that are identified in these experiments, the kinase(s) that target these sites are unknown. To broadly utilize available structural, functional, evolutionary, and contextual information in predicting kinase-substrate associations (KSAs), we develop a network-based machine learning framework. Our framework integrates a multitude of data sources to characterize the landscape of functional relationships …

Accucalc: A Python Package For Accuracy Calculation In Gwas, Jana Biová, Nicholas Dietz, Yen On Chan, Trupti Joshi, Kristin Bilyeu, Mária Škrabišová

Biomedical Sciences

The genome-wide association study (GWAS) is a popular genomic approach that identifies genomic regions associated with a phenotype and, thus, aims to discover causative mutations (CM) in the genes underlying the phenotype. However, GWAS discoveries are limited by many factors and typically identify associated genomic regions without the further ability to compare the viability of candidate genes and actual CMs. Therefore, the current methodology is limited to CM identification. In our recent work, we presented a novel approach to an empowered “GWAS to Genes” strategy that we named Synthetic phenotype to causative mutation (SP2CM). We established this strategy to identify …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

A Standardized Pipeline For Isolation And Assembly Of Genomes From Symbiotic Bacteria In Whole Louse Genomic Sequence Data., Mohammad Mikail I. Bala

Theses and Dissertations

Many insects are known to harbour intracellular and heritable bacteria (endosymbionts), which provide their hosts with adaptive traits. Whole insect gDNA shotgun sequencing projects often sequence the genome of endosymbiont, in addition to the insect’s genome. There are approximately 600 whole genome shotgun libraries from insects available on the public repository (NCBI), which can be mined to obtain endosymbiont genomes. The assembly and annotation of endosymbiont genomes can contribute towards the exploration of their role as obligate symbiotic partners. However, de novo assembly of an endosymbiont genome, continues to be challenging, when the host and/or enteric bacterial gDNA is present …

Adjusting For Gene-Specific Covariates To Improve Rna-Seq Analysis, Hyeongseon Jeon, Kyu-Sang Lim, Yet Nguyen, Dan Nettleton

Mathematics & Statistics Faculty Publications

Summary

This paper suggests a novel positive false discovery rate (pFDR) controlling method for testing gene-specific hypotheses using a gene-specific covariate variable, such as gene length. We suppose the null probability depends on the covariate variable. In this context, we propose a rejection rule that accounts for heterogeneity among tests by employing two distinct types of null probabilities. We establish a pFDR estimator for a given rejection rule by following Storey's q-value framework. A condition on a type 1 error posterior probability is provided that equivalently characterizes our rejection rule. We also present a suitable procedure for selecting a tuning …

Intergenic Transcription In In Vivo Developed Bovine Oocytes And Pre-Implantation Embryos, Saurav Ranjitkar, Mohammad Shiri, Jiangwen Sun, Xiuchun Tian

Computer Science Faculty Publications

Background

Intergenic transcription, either failure to terminate at the transcription end site (TES), or transcription initiation at other intergenic regions, is present in cultured cells and enhanced in the presence of stressors such as viral infection. Transcription termination failure has not been characterized in natural biological samples such as pre-implantation embryos which express more than 10,000 genes and undergo drastic changes in DNA methylation.

Results

Using Automatic Readthrough Transcription Detection (ARTDeco) and data of in vivo developed bovine oocytes and embryos, we found abundant intergenic transcripts that we termed as read-outs (transcribed from 5 to 15 kb after TES) and …

An Approach To Developing Benchmark Datasets For Protein Secondary Structure Segmentation From Cryo-Em Density Maps, Thu Nguyen, Yongcheng Mu, Jiangwen Sun, Jing He

Computer Science Faculty Publications

More and more deep learning approaches have been proposed to segment secondary structures from cryo-electron density maps at medium resolution range (5--10Å). Although the deep learning approaches show great potential, only a few small experimental data sets have been used to test the approaches. There is limited understanding about potential factors, in data, that affect the performance of segmentation. We propose an approach to generate data sets with desired specifications in three potential factors - the protein sequence identity, structural contents, and data quality. The approach was implemented and has generated a test set and various training sets to study …

Dfhic: A Dilated Full Convolution Model To Enhance The Resolution Of Hi-C Data, Bin Wang, Kun Liu, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Hi-C technology has been the most widely used chromosome conformation capture(3C) experiment that measures the frequency of all paired interactions in the entire genome, which is a powerful tool for studying the 3D structure of the genome. The fineness of the constructed genome structure depends on the resolution of Hi-C data. However, due to the fact that high-resolution Hi-C data require deep sequencing and thus high experimental cost, most available Hi-C data are in low-resolution. Hence, it is essential to enhance the quality of Hi-C data by developing the effective computational methods.

Results: In this work, we propose …

Cellbrf: A Feature Selection Method For Single-Cell Clustering Using Cell Balance And Random Forest, Yunpei Xu, Hong-Dong Li, Cui-Xiang Lin, Ruiqing Zheng, Yaohang Li, Jinhui Xu, Jianxin Wang

Computer Science Faculty Publications

Motivation

Single-cell RNA sequencing (scRNA-seq) offers a powerful tool to dissect the complexity of biological tissues through cell sub-population identification in combination with clustering approaches. Feature selection is a critical step for improving the accuracy and interpretability of single-cell clustering. Existing feature selection methods underutilize the discriminatory potential of genes across distinct cell types. We hypothesize that incorporating such information could further boost the performance of single cell clustering. Results

We develop CellBRF, a feature selection method that considers genes’ relevance to cell types for single-cell clustering. The key idea is to identify genes that are most important for discriminating …