Bioinformatics Commons^™

A Framework For The Statistical Analysis Of Mass Spectrometry Imaging Experiments, Kyle Bemis

Open Access Dissertations

Mass spectrometry (MS) imaging is a powerful investigation technique for a wide range of biological applications such as molecular histology of tissue, whole body sections, and bacterial films , and biomedical applications such as cancer diagnosis. MS imaging visualizes the spatial distribution of molecular ions in a sample by repeatedly collecting mass spectra across its surface, resulting in complex, high-dimensional imaging datasets. Two of the primary goals of statistical analysis of MS imaging experiments are classification (for supervised experiments), i.e. assigning pixels to pre-defined classes based on their spectral profiles, and segmentation (for unsupervised experiments), i.e. assigning pixels to newly …

Bayesian Causal Inference Of Cell Signal Transduction From Proteomics Experiments, Robert D. O. Ness

Open Access Dissertations

Cell signal transduction describes how a cell senses and processes signals from the environment using networks of interacting proteins. In computational systems biology, investigators apply machine learning methods for causal inference to develop causal Bayesian network models of signal transduction from experimental data. Directed edges in the network represent causal regulatory relationships, and the model can be used to predict the effects of interventions to signal transduction. Causal inference approaches applied to proteomics experiments use statistical associations between observed signaling protein concentrations to infer a causal Bayesian network model, but there is no experimental and analysis framework for applying these …

Dynamic Regulation Of Dna Demethylation And Rna-Directed Dna Methylation In Arabidopsis, Kai Tang

Open Access Dissertations

DNA methylation is an important epigenetic mark present in many eukaryotes, and is involved in many crucial biological processes, such as gene imprinting, regulation of gene expression, and genome stability. Proper genomic DNA methylation patterns are achieved through the concerted action of DNA methylation and demethylation pathways. In the model plant species Arabidopsis thaliana, ROS1 (REPRESSOR OF SILENCING 1) is one of the DNA demethylases and the key component in the demethylation pathway. Dysfunction of ROS1 leads to increase in DNA methylation level at thousands of genomic loci. However, the features of ROS1 targets are not well understood. In the …

Graphical Methods In Rna Structure Matching, Jiajie Huang

Open Access Dissertations

Eukaryotic genomes are pervasively transcribed; almost every base can be found in an RNA transcript. This is a surprising observation since most of the genome does not encode proteins. This RNA must serve an important regulatory function – important because producing non-coding RNA is an energy intensive process, and in the absence of strong selection one would expect it to disappear.

RNA families with common functions have specifically conserved structural motifs, which are directly related to the functional roles of RNA in catalysis and regulation. Because the conserved structures depend on base-pairing, similar RNA structures may have little or no …

Computational Labeling, Partitioning, And Balancing Of Molecular Networks, Biaobin Jiang

Open Access Dissertations

Recent advances in high throughput techniques enable large-scale molecular quantification with high accuracy, including mRNAs, proteins and metabolites. Differential expression of these molecules in case and control samples provides a way to select phenotype-associated molecules with statistically significant changes. However, given the significance ranking list of molecular changes, how those molecules work together to drive phenotype formation is still unclear. In particular, the changes in molecular quantities are insufficient to interpret the changes in their functional behavior. My study is aimed at answering this question by integrating molecular network data to systematically model and estimate the changes of molecular functional …

Understanding Plant Response To Stress Using Gene Model Quality Evaluation And Transcriptome Analysis, Karthik Ramaswamy Padmanabhan

Open Access Dissertations

The overall aim of the project was to understand how plants reacted to environmental stress and evolved to overcome it. The land plants that we see today evolved from a green algal ancestor around 510 million years ago. Plants had to make significant changes to their cellular, morphological, regulatory and physiological processes during their adaptation to the terrestrial environment from an aquatic environment. The first part of the project was to find out how these changes were reflected on the protein makeup of the early land plants. The gene model sequence data of two early land plants, Physcomitrella patens (moss) …

Physiological Bases And A Novel Genetic Determinant Of Water-Use Efficiency (Wue), Jie Yin

Open Access Dissertations

Water-use efficiency (WUE), the ratio of biomass to water loss, is a heritable but complex trait, the genetic basis of which is largely unknown. We utilized diverse accessions of the halophyte Eutrema salsugineum to ultimately identify a novel genetic determinant of WUE. E. salsugineum accessions from locations with low water availability, temperature, and radiation have lower transpirational water loss and greater biomass, resulting in higher WUE. High-WUE accessions also have lower stomatal density and index and larger thinner leaves than low-WUE accessions. We identified 14,808 single nucleotide polymorphisms (SNPs) between two accessions of E. salsugineum,Shandong (SH) and Yukon (YK), …

The Application Of The Hadoop Software Framework In Bioinformatics Programs, Dan Wang

Open Access Dissertations

The project described in this dissertation proposal attempted to improve the efficiency and scalability performance as well as the usability and user experience of three Bioinformatics applications - DNA/peptide sequence similarity comparison, digital DNA library subtraction, and DNA/peptide sequence de-duplication - by 1) adopting the Hadoop MapReduce algorithms and distributed file system and 2) implementing the fully automated Hadoop programs into a user friendly graphical user interface (GUI). In addition, the researcher was also interested in investigating the advantages and limitations of applying the Hadoop software framework as a general methodology in parallelizing Bioinformatics programs.

After considering the original calculation …

Biophysical Studies Of The Allosteric Regulatory Mechanism Of Syk Tandem Sh2 Domains Interacting With Immunoreceptor Tyrosine-Based Activation Motifs, Chao Feng

Open Access Dissertations

The non-receptor spleen tyrosine kinase (Syk) is an important player in signal transduction from immunoreceptors to various downstream targets. It is widely expressed in both haematopoietic and epithelial cells. Syk disorder is closely related with many inflammatory and autoimmune diseases, as well as cancers.

Syk associates with immunoreceptors through its tandem SH2 domains (tSH2), which contain two SH2 domains connected by interdomain A. The association of Syk with immunoreceptors is regulated by Y130 phosphorylation in interdomain A. The unphosphorylated tSH2 can bind with the doubly phosphorylated immunoreceptor tyrosine-based activation motif (dp-ITAM) of the cytoplasmic domains of immunoreceptors with very high …

Prediction Of The Protein Complex Assembly Pathway Using Multiple Docking Algorithm, Yoichiro Togawa

Open Access Theses

Proteins often function as a complex of multiple subunits, and the quaternary structure is important for proper function. An ordered assembly pathway is one of the strategies nature has developed to obtain the correct conformation: studies have shown a relationship between the assembly pathway and evolution of protein complexes. Identification of the assembly pathway and the intermediate structures helps drug development as well. Therefore, elucidation of the assembly pathway of protein complexes is important for understanding biochemical processes central to cellular function. Recent studies have demonstrated the assembly pathway of a protein complex can be predicted from its crystal structure …

Estimation Of Variation For High-Throughput Molecular Biological Experiments With Small Sample Size, Danni Yu

Open Access Dissertations

Motivation: In the quantification of molecular components, a large variation can affect and even potentially mislead the biological conclusions. Meanwhile, the high-throughput experiments often involve a small number of samples due to the limitation of cost and time. In such cases, the stochastic information may dominate the outcome of an experiment because there may not be enough samples to present the true biological information. It is challenging to distinguish the changes in phenotype from the stochastic variation.

Methods: Since the biological molecules have been quantified with different technologies, different statistical methods are required. Focusing on three types of important high-throughput …

Development Of Tyrosine Kinase Peptide Biosensors And Methods For Detection, Andrew Michael Lipchik

Open Access Dissertations

New methods to monitor tyrosine kinase activity are critical for studying kinases in cell biology, drug discovery and the clinic. Peptide-based biosensors for detection of kinase activity utilitize a kinase specific artificial peptide substrate, which can report intercellular kinase activity through the incorporation of phosphate.

An artificial Syk substrate peptide was developed and incorporated with other functional modules to produce a Syk biosensor. These modules included a biotin-tag for affinity capture, a photo-cleavable amino acid to allow release of the substrate from the delivery module and the cell penetrating peptides TAT. A live cell kinase assay utilizing this biosensor was …