No description available.

The DNA in the eukaryotic genome is wrapped in 147--bp segments around an octamer of histone proteins to form the fundamental subunit of chromatin, the nucleosome. Nucleosomes regulate the access of proteins to DNA, thus regulating important DNA-templated events such as transcription, translation, recombination, and repair. In order to characterize the chromatin landscape in maize, we mapped nucleosome positions using micrococcal nuclease (MNase) to enrich for nucleosomal DNA. We mapped nucleosomes under a variety of experimental conditions and in different tissues. We identified an unexpected, nonuniform source of variation which we traced to the degree to which chromatin is digested with MNase. We exploited this property to identify nucleosomes in the maize genome that possessed unique biochemical traits as being hypersensitive or hyper-resistant to MNase digestion. These regions were associated with important biological processes, including gene expression levels, transcription-factor binding, and highly-conserved noncoding sequences. In addition, we found that these nucleosomes displayed tissue specificity, implicating this special type of chromatin feature in regulating gene expression under different cell physiologies. We extended this work to the human genome and made similar discoveries: hypersensitive nucleosomes were associated with gene expression levels and were enriched in important regulatory elements. We also found hyper-resistant nucleosomes to be highly-associated with paused RNA polymerase II, implicating these nucleosomes in regulating transcriptional elongation. Thus, our approach to chromatin profiling uncovers novel biochemical states of multicellular organisms that are likely important for transcription, differentiation, and cellular responses. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester, 2014. / November 10, 2014. / chromatin, genomics, microarrays, MNase-seq, ngs, nucleosome / Includes bibliographical references. / Hank Bass, Professor Co-Directing Dissertation; Jonathan Dennis, Professor Co-Directing Dissertation; Jinfeng Zhang, University Representative; Brian Chadwick, Committee Member; Dave Gilbert, Committee Member.

Big data has brought both opportunities and challenges to our research community. Complex models can be built with large volumes of data researchers have never had access before. In this study we explore the structure learning of Bayesian network (BN) and its application to reverse engineering of gene regulatory networks (GRNs). A Bayesian network is a graphical representation of a joint distribution that encodes the conditional dependencies and independencies among the variables. We proposed a novel three-stage BN structure learning method, called GRASP (GRowth-based Approach with Staged Pruning). In the first stage, a new skeleton (undirected edges) discovery method, double filtering (DF), was designed. Compared to existing methods, DF requires smaller sample sizes to achieve similar statistical power. Based on the skeleton estimated in the first step, we proposed a sequential Monte Carlo (SMC) method to sample the edges and their directions to optimize a BIC-based score. SMC method has less tendency to be trapped in local optima, and the computation is easily parallelizable. On the third stage, we reclaim the edges that may be missed from previous stages. We obtained satisfactory results from simulation study and applied the method to infer GRNs from real experimental data. A method on personalized chemotherapy regimen selection for breast cancer and a novel algorithm for relationship extraction from unstructured documents will be discussed as well. / A Dissertation submitted to the Department of Statistics in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester 2016. / March 22, 2016. / Bayesian network structure learning, Neoadjuvent chemotherapy, Protein-protein-interaction, sequential Monte Carlo / Includes bibliographical references. / Jinfeng Zhang, Professor Directing Dissertation; Qing-Xiang Amy Sang, University Representative; Adrian Barbu, Committee Member; Yiyuan She, Committee Member; Debajyoti Sinha, Committee Member.

In the United States approximately 17,000 new spinal cord injury cases occur annually. Even with timely medical interventions, the primary injury is often exacerbated by a period of inflammation and pathological vascular changes that result in additional secondary tissue injuries. Moreover, significant cellular death in the injured cord produces cell debris that can contribute to secondary damage if not promptly cleared. Our investigations demonstrate that bone marrow-derived macrophages (BMDMs), but not resident microglia, are the primary phagocytes that clear cell debris from the injured cord. Furthermore, BMDM are retained in the lesion epicenter for protracted periods of time following engulfment of myelin debris. The BMDMs subsequently become myelin laden macrophages which are detrimental to recovery. To study the effects of myelin debris on macrophages, we have developed in vitro methods that allow the quantification of myelin debris phagocytosis and lipid retention. We also identified myelin debris as a potent non-canonical survival factor that can support long-term BMDM survival and prolong their potential to induce damage in vivo. Moreover, we demonstrate for the first time that myelin basic protein (MBP), is sufficient to suppress BMDM apoptosis. To explore both the inflammatory activation and survival of BMDMs we used RNA-sequencing to profile the transcriptome of BMDMs treated with myelin debris and MBP as well as pro-inflammatory (M1) and anti-inflammatory (M2) stimuli. Pathway analysis reveals several key anti-apoptotic genes up-regulated by both myelin debris and MBP. These represent potential therapeutic targets to reduce prolonged macrophage presence in the lesion. We additionally found that myelin debris stimulated macrophages, while functionally pro-inflammatory, have a transcriptional profile that is distinct from classic M1 macrophages. Collectively, these findings expand our understanding of infiltrating BMDMs in SCI, and reveal novel targets for therapeutic manipulation of immune responses to limit secondary injuries and promote recovery. / A Dissertation submitted to the Department of Biomedical Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester 2019. / February 1, 2019. / Bioinformatics, Inflammation, Macrophage, Myelin Basic Protein, Myelin Debris, Spinal Cord Injury / Includes bibliographical references. / Yi Ren, Professor Directing Dissertation; James Fadool, University Representative; Richard Nowakowski, Committee Member; Cathy Levenson, Committee Member; David Meckes, Committee Member.

I692: Project in Bioinformatics August 2005 / Objective: Literature review to evaluate the extent to which Bioinformatics has facilitated the drug discovery and development process from an economic perspective Problem: A plethora of genomic and proteomic information was uncovered by the U.S Human Genome Project (HGP). Despite the projected impact that Bioinformatics and Pharmacogenomics were projected to have in the drug discovery and development process, the challenges facing the pharmaceutical companies – in this regard, still persist. Design: An extensive integrated literature review of library resources such as MEDLINE, ERIC, PsychInfo, EconLit, Social Services Abstracts, ABI/INFORM and LISA (all 1990 – Present). These electronic databases were researched because of their focuses on the healthcare sector, medical and scientific innovations, economic modeling and analysis, bioinformatics and computational biology, applied social research and technology applications. Semi-structured interviews of Bioinformatics professionals were also conducted to complement the literature review. Also, Internet-based databases from reliable resources were also researched resulting in serendipitous discoveries. Sample: Published English language reports of studies and research carried out worldwide from 1990 to 2004, relating to drug discovery and development. Selection criteria: Primary focus was on research publications and journals that identify and discuss the practice of Bioinformatics, especially in the area of drug discovery and development. Premium was placed on articles and publications that discussed the economic impacts of Bioinformatics in the drug discovery process. Results: Though the goals of Bioinformatics have been clearly defined, and the discipline is widely practiced in the pharmaceutical industry, this study has not found any definite attempts to evaluate its economic and regulatory impact specifically in facilitating the drug discovery and development process, and the delivery of personalized drugs. Discussion: Bioinformatics and Pharmacogenomics are the new facets of the ever-evolving drug discovery and development process. It may still be a while before their full impact and potential is attained.

No description available.

No description available.

No description available.

No description available.

No description available.