Bioinformatics Commons^™

Bilinear Programming And Protein Structure Alignment, J. Cain, D. Kamenetsky, N. Lavine

Mathematical Sciences Technical Reports (MSTR)

Proteins are a primary functional component of organic life, and understanding their function is integral to many areas of research in biochemistry. The three-dimensional structure of a protein largely determines this function. Protein structure alignment compares the structure of a protein with known function to that of a protein with unknown function. A protein’s three-dimensional structure can be transformed through a smooth piecewise-linear sigmoid function to a real symmetric contact matrix that represents the functional significance of certain parts of the protein. We address the protein alignment problem as a minimization of the 2-norm difference of two proteins’ contact matrices. …

An Analysis Of Global Gene Expression Resulting From Exposure To Energetic Materials, Vernon L. Mcintosh Jr.

Doctoral Dissertations

AN ANALYSIS OF GLOBAL GENE EXPRESSION RESULTING FROM EXPOSURE TO ENERGETIC MATERIALS

A Dissertation

Presented for the Doctor of Philosophy Degree

University of Tennessee, Knoxville

VERNON LASHAWN MCINTOSH JR.

August 2010

Dedication

This dissertation is dedicated to my family. My mother and father Debra and Vernon McIntosh instilled in me the respect for academic excellence and the drive maximize my potential. Early on, my younger brother Kyle started showing signs of a shared interest in biology thus my desire to be a positive role model for him kept me motivated. Last but certainly not least, my loving wife and best …

The Maximum Clique Problem: Algorithms, Applications, And Implementations, John David Eblen

Doctoral Dissertations

Computationally hard problems are routinely encountered during the course of solving practical problems. This is commonly dealt with by settling for less than optimal solutions, through the use of heuristics or approximation algorithms. This dissertation examines the alternate possibility of solving such problems exactly, through a detailed study of one particular problem, the maximum clique problem. It discusses algorithms, implementations, and the application of maximum clique results to real-world problems. First, the theoretical roots of the algorithmic method employed are discussed. Then a practical approach is described, which separates out important algorithmic decisions so that the algorithm can be easily …

Cross-Market Model Adaptation With Pairwise Preference Data For Web Search Ranking, Jing Bai, Fernando Diaz, Yi Chang, Zhaohui Zheng, Keke Chen

Kno.e.sis Publications

Machine-learned ranking techniques automatically learn a complex document ranking function given training data. These techniques have demonstrated the effectiveness and flexibility required of a commercial web search. However, manually labeled training data (with multiple absolute grades) has become the bottleneck for training a quality ranking function, particularly for a new domain. In this paper, we explore the adaptation of machine-learned ranking models across a set of geographically diverse markets with the market-specific pairwise preference data, which can be easily obtained from clickthrough logs. We propose a novel adaptation algorithm, Pairwise-Trada, which is able to adapt ranking models that are trained …

Pattern Space Maintenance For Data Updates And Interactive Mining, Mengling Feng, Guozhu Dong, Jinyan Li, Yap-Peng Tan, Limsoon Wong

Kno.e.sis Publications

This article addresses the incremental and decremental maintenance of the frequent pattern space. We conduct an in-depth investigation on how the frequent pattern space evolves under both incremental and decremental updates. Based on the evolution analysis, a new data structure, Generator-Enumeration Tree (GE-tree), is developed to facilitate the maintenance of the frequent pattern space. With the concept of GE-tree, we propose two novel algorithms, Pattern Space Maintainer+ (PSM+) and Pattern Space Maintainer− (PSM−), for the incremental and decremental maintenance of frequent patterns. Experimental results demonstrate that the proposed algorithms, on average, outperform the representative state-of-the-art …

Comparative Functional Genomic Study Of Substrate Specificity Evolution Of The Sabath Family Of Methyltransferases In Plants, Nan Zhao, Jean-Luc Ferrer, Xiaofeng Zhuang, Feng Chen

Plant Sciences Publications and Other Works

Background

The plant SABATH protein family is composed of a group of related small molecule methyltransferases (MTs) that catalyze the S-adenosyl-L-methionine dependent methylation of a variety of plant small molecular weight metabolites encompassing widely divergent structures. Some of these substrates are important plant hormones and signaling molecules, such as indole-3-acetic acid (IAA), jasmonic acid (JA) and salicylic acid (SA). Methylating these compounds may have important impacts on plant growth and development. In the previous paper, we presented Indole-3-acetic acid (IAA) methyltransferase (IAMT) as an evolutionarily ancient member of the SABATH family in higher plants. Whether the IAMT exists in less …

Graph Algorithms For Machine Learning: A Case-Control Study Based On Prostate Cancer Populations And High Throughput Transcriptomic Data, Gary L. Rogers, Pablo Moscato, Michael A. Langston

Faculty Publications and Other Works -- EECS

Background

The continuing proliferation of high-throughput biological data promises to revolutionize personalized medicine. Confirming the presence or absence of disease is an important goal. In this study, we seek to identify genes, gene products and biological pathways that are crucial to human health, with prostate cancer chosen as the target disease.

Materials and methods

Using case-control transcriptomic data, we devise a graph theoretical toolkit for this task. It employs both innovative algorithms and novel two-way correlations to pinpoint putative biomarkers that classify unknown samples as cancerous or normal.

Results and conclusion

Observed accuracy on real data suggests that we are …

Serendipitous Discoveries In Microarray Analysis, Sally R. Ellingson, Charles A. Phillips, Randy Glenn, Douglas Swanson, Thomas Ha, Daniel Goldowitz, Michael A. Langston

Faculty Publications and Other Works -- EECS

Background

Scientists are capable of performing very large scale gene expression experiments with current microarray technologies. In order to find significance in the expression data, it is common to use clustering algorithms to group genes with similar expression patterns. Clusters will often contain related genes, such as co-regulated genes or genes in the same biological pathway. It is too expensive and time consuming to test all of the relationships found in large scale microarray experiments. There are many bioinformatics tools that can be used to infer the significance of microarray experiments and cluster analysis.

Materials and methods

In this project …

Body Mass Index, Treatment Practices, And Mortality In Patients With Acute Heart Failure, Timothy Fitzgibbons, Olga Hardy, Darleen Lessard, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVES: Obesity is associated with an increased risk of heart failure (HF). Among patients presenting with acute HF, however, differences in clinical characteristics, treatment regimens, and short-term prognosis of varying weights are largely unknown, particularly from a broader population-based perspective. METHODS: A total of 3722 patients admitted with acute HF to 11 greater Worcester (Massachusetts, USA) hospitals during 1995 and 2000 were categorized as being lean (n = 216), normal weight (n = 1465), overweight (n = 1007), or obese (n = 1034) at the time of hospitalization. RESULTS: Obese patients with decompensated HF were significantly younger (mean age = …

Prognosis Of Acute Myocardial Infarction Complicated By Complete Heart Block (The Worcester Heart Attack Study), Robert Goldberg, Juan Zevallos, Jorge Yarzebski, Joseph Alpert, Joel Gore, Z. Chen, James Dalen

Jorge L. Yarzebski

As part of a community-based study of patients hospitalized with acute myocardial infarction (AMI) in the Worcester, Massachusetts, metropolitan area, changes over time in the incidence rates of complete heart block (CHB) complicating AMI, and the prognostic impact of CHB on the in-hospital and long-term survival of these patients were examined. In all, 4,762 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area during 1975, 1978, 1981, 1984, 1986 and 1988 constituted the study sample. The incidence rates of CHB complicating AMI remained relatively stable at 5.8% over the 13-year (1975 to 1988) period studied. The …

Changes Over Time In The Use Of Aspirin In Patients Hospitalized With Acute Myocardial Infarction (1975 To 1997): A Population-Based Perspective, Elizabeth Jackson, Ramya Sivasubramian, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVE: The purpose of this study was to examine 2 decade-long trends in the use of aspirin and associated outcomes in patients hospitalized with acute myocardial infarction. BACKGROUND: Aspirin has been shown to be beneficial in the secondary prevention of AMI. However, little is known about changes over time in the use of aspirin in patients hospitalized with AMI and associated outcomes, particularly from a more generalizable population-based perspective. METHODS: We examined trends in aspirin use and hospital and long-term outcomes in 9336 metropolitan Worcester, Mass, residents hospitalized with validated AMI in all area hospitals between 1975 and 1997. RESULTS: …

Thirty-Year Trends (1975-2005) In The Magnitude, Patient Characteristics, And Hospital Outcomes Of Patients With Acute Myocardial Infarction Complicated By Ventricular Fibrillation, Robert Goldberg, Jorge Yarzebski, Frederick Spencer, Juan Zevallos, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

Limited contemporary data are available describing the incidence rates, hospital prognosis, and factors associated with the occurrence of ventricular fibrillation (VF) in patients hospitalized with acute myocardial infarction (AMI). The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the magnitude, predictors, and hospital case-fatality rates associated with VF in residents of a large New England metropolitan area hospitalized at all area medical centers with an uncomplicated AMI. The study population consisted of 7,472 residents of the Worcester (Massachusetts) metropolitan area hospitalized with an uncomplicated AMI in 15 annual periods from 1975 to 2005. The overall …

Temporal Trends (1975 Through 1990) In The Incidence And Case-Fatality Rates Of Primary Ventricular Fibrillation Complicating Acute Myocardial Infarction. A Communitywide Perspective, David Chiriboga, Jorge Yarzebski, Robert Goldberg, Joel Gore, Joseph Alpert

Jorge L. Yarzebski

BACKGROUND: As part of a population-based study of acute myocardial infarction, we examined changes over time in the incidence and in-hospital case-fatality rates of primary ventricular fibrillation complicating acute myocardial infarction. METHODS AND RESULTS: Patients with validated acute myocardial infarction hospitalized at 16 hospitals in the Worcester, Mass, metropolitan area between 1975 and 1990 comprised the study sample. During the 15-year study period, 5.1% of patients developed primary ventricular fibrillation in the setting of uncomplicated acute myocardial infarction, with this rate remaining relatively constant over time. Both age- and multivariable-adjusted analyses showed no significant trend in the incidence rates of …

Long-Term Trends (1986-2003) In The Use Of Coronary Reperfusion Strategies In Patients Hospitalized With Acute Myocardial Infarction In Central Massachusetts, Robert J. Goldberg, Frederick A. Spencer, Joseph Okolo, Darleen M. Lessard, Jorge L. Yarzebski, Joel M. Gore

Jorge L. Yarzebski

BACKGROUND: The objectives of our study were to examine long-term (1986-2003) trends in the use of percutaneous coronary interventions (PCI) and thrombolytic therapy in the management of patients hospitalized at all Central Massachusetts medical centers with acute myocardial infarction (AMI). Our secondary study goal was to examine factors associated with use of these coronary reperfusion strategies. Limited contemporary data are available about changing trends in the use of coronary reperfusion strategies, particularly from a population-based perspective. METHODS: The sample consisted of 9422 greater Worcester (MA) residents hospitalized with AMI at all metropolitan Worcester medical centers in 10 annual periods between …

A Community-Wide Perspective Of Gender Differences And Temporal Trends In The Use Of Diagnostic And Revascularization Procedures For Acute Myocardial Infarction, David Chiriboga, Jorge Yarzebski, Robert Goldberg, Z. Chen, Jerry Gurwitz, Joel Gore, Joseph Alpert, James Dalen

Jorge L. Yarzebski

This study compares the overall use, as well as temporal trends, of various diagnostic and revascularization procedures for acute myocardial infarction (AMI) in men and women. The study sample comprised a total of 2,924 men and 1,838 women with validated AMI admitted to any of the 16 teaching and community hospitals in the Worcester, Massachusetts, metropolitan area during 1975, 1978, 1981, 1984, 1986 and 1988. During the period under study there was a significant increase in use of each of the examined procedures during hospitalization for AMI in both men and women. Increasing use of multiple procedures was also seen …

Temporal Trends And Associated Factors Of Inpatient Cardiac Rehabilitation In Patients With Acute Myocardial Infarction: A Community-Wide Perspective, Frederick Spencer, Bobak Salami, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

PURPOSE: Cardiac rehabilitation (CR) has been shown to be an important therapeutic intervention after the development of acute myocardial infarction (AMI), but historically has been underused. Inpatient CR often represents cardiac patients' first exposure to risk factor modification education and acts as a gateway to outpatient programs. METHODS: The authors performed a longitudinal study of the use of inpatient CR in 5204 Worcester residents hospitalized with validated AMI in seven 1-year periods between 1986 and 1997. RESULTS: The overall rate of referral to inpatient CR was 68%, with a slight decline in use to less than 60% in the authors' …

Communitywide Trends In The Use And Outcomes Associated With Beta-Blockers In Patients With Acute Myocardial Infarction: The Worcester Heart Attack Study, Helme Silvet, Frederick Spencer, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Despite the benefits associated with beta-blocker therapy in patients with acute myocardial infarction (AMI), limited recent data are available describing the extent of use of this therapy and the associated hospital and long-term outcomes, particularly from the perspective of a population-based study. Data are also limited about the characteristics of patients with AMI who do not receive beta-blockers. This study examines more than 2 decades of trends in the use of beta-blockers in hospitalized patients with AMI. METHODS: Communitywide study of 10,374 patients hospitalized with confirmed AMI in all metropolitan Worcester hospitals during 12 annual periods between 1975 and …

The Impact Of The Stent Era On The Management Strategy For Acute Myocardial Infarction: A Population-Based Perspective, Harold Dauerman, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

We determined trends in the use of invasive diagnostic and revascularization strategies from a multihospital community-wide perspective for patients suffering acute myocardial infarction (AMI). Comparing 3,824 patients treated in the prestent era (1986-1993) to 1,915 patients hospitalized during the stent era (1995-1997), there was a significant increase in the use of invasive procedures and revascularization techniques across a broad spectrum of AMI patients during their index hospitalization. This resulted in a higher-risk profile of patients referred for invasive management of AMI in the stent era. Cathet. Cardiovasc. Intervent. 51:255-258, 2000.

Multidecade-Long Trends (1986-2005) In The Utilization Of Coronary Reperfusion And Revascularization Treatment Strategies In Patients Hospitalized With Acute Myocardial Infarction: A Community-Wide Perspective, Jared Wasser, Robert Goldberg, Frederick Spencer, Jorge Yarzebski, Joel Gore

Jorge L. Yarzebski

OBJECTIVES: The objectives of our community-wide investigation were to describe multidecade-long trends (1986-2005) in the utilization of thrombolytic therapy, percutaneous coronary interventions, and coronary artery bypass graft surgery in patients hospitalized with acute myocardial infarction (AMI). METHODS: The study sample consisted of 9422 greater Worcester (MA) residents hospitalized with confirmed AMI at all metropolitan Worcester medical centers in 11 annual periods between 1986 and 2005. RESULTS: Increases in the utilization of percutaneous coronary interventions were observed between 1986 (2.0%) and 2005 (50.7%) with the most rapid increases beginning in the late 1990s. Utilization of coronary artery bypass graft surgery during …

Two-Decade-Long Trends (1975-1997) In The Incidence, Hospitalization, And Long-Term Death Rates Associated With Complete Heart Block Complicating Acute Myocardial Infarction: A Community-Wide Perspective, Frederick Spencer, Samer Jabbour, Darleen Lessard, Jorge Yarzebski, Shmuel Ravid, Virginia Zaleskas, Michael Hyder, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: The purpose of this community-wide study was to describe a >2-decade-long experience (1975-97) in the incidence and death rates associated with complete heart block (CHB) in patients with acute myocardial infarction (AMI). Limited population-based data exist describing recent, and changes with time therein, incidence and case-fatality rates associated with CHB complicating AMI.

METHODS: We conducted an observational study of 9082 metropolitan Worcester, Mass, residents (1990 census = 437,000) hospitalized with validated AMI in all greater Worcester hospitals during 11 1-year periods between 1975 and 1997.

RESULTS: Overall, CHB developed in 5.0% of patients with AMI. The incidence rates of …