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Full-Text Articles in Bioinformatics

Chromatin Digestion By The Chemotherapeutic Agent Bleomycin Produces Nucleosome And Transcription Factor Footprinting Patterns Similar To Micrococcal Nuclease, Joshua Michael Stolz Sep 2019

Chromatin Digestion By The Chemotherapeutic Agent Bleomycin Produces Nucleosome And Transcription Factor Footprinting Patterns Similar To Micrococcal Nuclease, Joshua Michael Stolz

Theses and Dissertations

Bleomycin (BLM), a glycopeptide antibiotic commonly used in chemotherapeutic treatments, has been shown to produce single and double stranded DNA breaks. Subsequent analysis of DNA fragmentation patterns has demonstrated preferential digestion of chromatin in the TSS of active genes and the ability to produce nucleosome-sized fragments within intact chromatin. Nucleosome positioning plays a critical role in the regulation of gene activation. Currently, micrococcal nuclease (MNase) is used as the standard for mapping the position of nucleosomes in the genome. In order to identify whether BLM can be used as an effective nucleosome-mapping agent, BLM was used to digest chromatin in …


Understanding The Molecular And Cellular Functions Of Odd-Skipped Related 1 In Outflow Tract Development, Menglan Xiang Aug 2019

Understanding The Molecular And Cellular Functions Of Odd-Skipped Related 1 In Outflow Tract Development, Menglan Xiang

Theses and Dissertations

The cardiac outflow tract (OFT) is a transient conduit that connects the embryonic heart chambers to the vascular network. Transcription factor Osr1 promotes the proliferation and cell cycle progression of second heart field (SHF), an essential cell population that contribute to the developing OFT. In this study, we investigated the role of Osr1 in OFT development on cellular and molecular levels using a systems biology approach. We observed OFT rotation and elongation defects, as well as double-outlet right ventricle and overriding aorta as a result of SHF-specific deletion of Osr1. Using genetic inducible fate mapping, we showed that Osr1-expressing SHF …


An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese Jun 2019

An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese

Theses and Dissertations

The drug discovery process is an extremely long and expensive process that modern computational methods help to alleviate. Through the use of computational methods, we provide information and insight into the activation methods of class B GPCRs so that future drugs can be developed to have less side effects. The first study focuses on the corticotropin releasing factor receptor, which is a good drug target for anxiety and depression. A mechanism of activation was theorized which focuses less on molecular switches (as has been the focus of several papers) and more on large scale conformation at the intracellular region of …


Evolution Of Endurance Running Genes Across Primates, Natalia T. Grube Apr 2019

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 …


Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon Feb 2019

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

Theses and Dissertations

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.


Evaluating Predixcan’S Ability To Predict Differential Expression Between Alcoholics And Non-Alcoholics, John E. Drake Jr Jan 2019

Evaluating Predixcan’S Ability To Predict Differential Expression Between Alcoholics And Non-Alcoholics, John E. Drake Jr

Theses and Dissertations

PrediXcan is a recent software for the imputation of gene expression from genotype data alone. Using an overlapping set of transcriptome datasets from postmortem brain tissues of donors with alcohol use disorder and neurotypical controls, which were generated by two different platforms (e.g., Arraystar and Affymetrix), and an additional unrelated transcriptome dataset from lung tissue, we sought to evaluate PrediXcan’s ability to impute gene expression and identify differentially expressed genes. From the Arraystar platform, 1.3% of matched genes between the measured and imputed expression had a Pearson correlation ≥ 0.5. Our attempt to replicate this finding using the expression data …


Methods For Joint Normalization And Comparison Of Hi-C Data, John C. Stansfield Jan 2019

Methods For Joint Normalization And Comparison Of Hi-C Data, John C. Stansfield

Theses and Dissertations

The development of chromatin conformation capture technology has opened new avenues of study into the 3D structure and function of the genome. Chromatin structure is known to influence gene regulation, and differences in structure are now emerging as a mechanism of regulation between, e.g., cell differentiation and disease vs. normal states. Hi-C sequencing technology now provides a way to study the 3D interactions of the chromatin over the whole genome. However, like all sequencing technologies, Hi-C suffers from several forms of bias stemming from both the technology and the DNA sequence itself. Several normalization methods have been developed for normalizing …