MULTIGROUP DISCRIMINANT FUNCTION ANALYSIS FOR RACE AND SEX ASSESSMENT
James Taylor
Herbert H. Lehman College Office Of Grants And Contracts New York, Ny 10468
Grant 5S06GM008225-060002 from National Institute Of General Medical Sciences
Abstract: Our main objective has been to develop criteria for classifying and identifying human skeletal remains in forensic casework and in archaeological investigations. In the past this has focused on generating statistical criteria for assessing sex and face in contemporary and historic Black and White adult and fetal populations. We have conducted reliability studies on these criteria and are presently engaged in extending our research to include criteria for assessing handedness for identification purposes. The latter has implications relevant to the biomedical understanding of the interrelationships between laterality and osteoarthritis, and the necessary inclusion of age, race, and sex parameters in its study make it a natural extension of our earlier research. MBRS, MARC and numerous other honors level students have been involved in earlier versions of this research over the past several years. The raw materials of this research involve major museum collections, contact with forensic scientists and law enforcement officials and, in two cases, archaeological style investigations of older cemeteries. This mix of research materials and locations, coupled with the solid science of the statistical analyses, has proven a strong magnet for keeping students interested and involved in biomedical research.
Keywords: HEALTH SOCIAL CONTROL, FORENSIC MEDICINE, SOCIAL GROUPS, RACIAL STOCKS, body physical characteristics
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to James Taylor
PREVALENCE AND PROGNOSIS OF PULMONARY HYPERTENSION IN ADULTS WITH SICKLE CELL
James Taylor
N/a
Grant 1ZIAHL006012-01 from National Heart, Lung, And Blood Institute
Abstract: Sickle cell disease is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Mortality rates of sickle cell patients with pulmonary hypertension are hypothesized to be significantly increased as compared to patients without pulmonary hypertension. We have enrolled 449 patients in a study of the prevalence and prognosis of patients with sickle cell disease and pulmonary hypertension. All patients were screened with transthoracic echocardiograms and the tricuspid regurgitant jet velocity (TRV) used to estimate the pulmonary artery systolic pressure. Pulmonary hypertension was prospectively defined by a TRV >= 2.5 m/sec and severe pulmonary hypertension defined by a TRV >= 3.0 m/sec. Patients were followed for a mean of 18 months and censored at time of death or loss to follow-up. We performed and analyzed Doppler echocardiographic assessments of pulmonary artery systolic pressure in 235 consecutive patients (mean age=37.11 years). Doppler-defined pulmonary hypertension occurred in 32 percent of patients. Diastolic dysfunction was present in 18% of patients. A combination of diastolic dysfunction and pulmonary hypertension was present in 11% of patients, and diastolic dysfunction accounted for ony 10% to 20% of the variability in TR jet velocity. Diastolic dysfunction, as reflected by a low E/A ratio, was associated with mortality with a risk ratio of 3.5 (95% confidence interval 1.5 to 8.4, p<0.001), even after adjustment for TR jet velocity. The presence of both diastolic dysfunction and pulmonary hypertension conferred a risk ratio for death of 12.0 (95% confidence interval 3.8 to 38.1, p <0.001). Right heart catheterization was performed under a separate protocol in consenting patients with TRV >= 2.8 m/sec (based on the results of the screening echo). Based on these data, 32% of patients with sickle cell disease have elevated pulmonary artery systolic pressures (TRV >= 2.5 m/sec) and 9% have severely elevated pressures. Multiple-regression analysis identified increasing age, increased serum markers of hemolysis (LDH, total bilirubin) and arginine/ornithine ratio as significant independent predictors of pulmonary hypertension. Fetal hemoglobin levels did not predict pulmonary hypertension nor did hydroxyurea therapy modify pulmonary pressures. Left ventricular dysfunction was rarely observed (< 2% of patients) and calculated pulmonary artery systolic pressures based on TRV accurately predicted measured values during right heart catheterization (r=0.98; p=0.001). The patients diagnosed with pulmonary hypertension had significantly greater mortality. These studies suggest that secondary pulmonary hypertension is common in adult patients with sickle cell disease, appears to be resistant to hydroxyurea therapy, is linked to hemolysis and is associated with a high mortality. These data suggest that all patients should be screened for this complication and considered for therapeutic trials with oxygen, anticoagulation, transfusion and/or selective pulmonary vasodilators. 491 subjects have enrolled in this study to date and we continue to enroll approximately 8 new subjects per month. Subjects continue to be enrolled in this trial and referred for treatment studies if identified with pulmonary hypertension. We have also enrolled 66 African American controls to determine the normal range of tricuspid regurgitant jet velocity who serve as a comparison for the sickle cell population being studied. The two tests below were added and are currently being performed on all initial visits and on follow-up visits occurring at 2, 4, 6, etc. years (1) Peripheral Arterial Tonometry (PAT) (ENDO-PAT 2000, Itamar Medical) is a relatively new, FDA-approved noninvasive technology that captures a beat-to-beat plethysmographic recording of the finger arterial pulse wave activity with pneumatic probes. The PAT score (ratio of finger blood flow amplitude before and after blood flow occlusion) will be analyzed for correlation with tricuspid regurgitant jet velocity, as well as other clinical laboratory and research markers obtainned in this study. This is a hypothesis generating analysis for future potential studies. (2) The passive infrared photography may be administered to subjects enrolled in this protocol. A non-invasive, real-time, in vivo imaging system has been developed for directly determining the spatial distributions of blood flow, by measuring the emission infrared emission from the skin of an individual. During Infrared (IR) photography images will be collected during 7-20 min and analyzed using imaging software. The software is capable of extracting temperature variations from collected 3D image cube and to identify for any chosen region of interest the low frequency temperature oscillations (0.017 Hz) using Fast Fourier Transformation and Wavelet analysis. Calculated power spectrum will reflect frequencies at which blood flow oscillates. At the end of analysis, a synthesized image will represent the spatial distribution and amplitude of oscillations at a given frequency. Such very low frequency oscillations have been characterized by laser Doppler flowmetry (point measurement) as related to endothelial function, NO dependent, increased with cholinergic stimulation, and potential to be a noninvasive marker for NO-dependent microvascular reactivity. IR photography is a passive method, provides a new information on spatial extend of flow oscillation and more safe and easy to use in the clinic. This year we added the Pittsburgh Sleep Quality Index and Beck Depression Inventory This is being used to assess the co-morbidity of depression and sleep disturbances of subjects with and without pulmonary hypertension. The subjects receive both The Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Beck Depression Inventory questionnaire upon initial evaluation or their scheduled follow-up visit every 2 years. They are asked to complete the BDI questionnaire in clinic and return it to a member of the study team. That questionnaire is then scored while the subjects are in clinic and Dr. Jeffrey Schulden is in clinic to see any subject whose responses indicate tendency toward depression or suicidal ideation. The PSQI questionnaire may be completed in clinic or taken home, completed and returned to us by mail
Keywords: 2, 5-Diaminopentanoic Acid; 21+ years old; 3D image; Accounting; Active Follow-up; Adult; Affect; African American; Afro American; Afroamerican; Age; Allele Frequency; Anticoagulation; Arginine; Arginine, L-Isomer; B-globin; Beck depression inventory; Bilirubin, total measurement; Black Populations; Black or African American; Blood Cell Count, White; Blood Vessels; Blood flow; CD106; CD106 Antigens; Candidate Disease Gene; Candidate Gene; Cardiac Catheterization Procedures; Catheterization, Cardiac; Cessation of life; Clinic; Clinical; Clinical Trials, Therapy; Collection; Complication; Computer Programs; Computer software; Confidence Intervals; Consent; Control Groups; Cross-Product Ratio; DNA; Data; Death; Deoxyribonucleic Acid; Development; Diagnosis; Disease; Disorder; Drug Kinetics; Drugs; Dysfunction; Echocardiogram; Echocardiography; Enrollment; Evaluation; FDA approved; Feeling suicidal; Fetal Hemoglobin; Fingers; Forecast of outcome; Frequencies (time pattern); Frequency; Functional disorder; Future; Gene Frequency; Genes; Genetic; Genetic Condition; Genetic Diseases; Genetic Polymorphism; Genetic analyses; Genotype; Hb SS disease; HbSS disease; Heart Catheterization; Heart Catheterization Pocedure; Hemoglobin F; Hemoglobin H Disease; Hemoglobin S Disease; Hemoglobin concentration result; Hemoglobin sickle cell disease; Hemoglobin sickle cell disorder; Hemolysis; Hereditary Disease; Home; Home environment; Human, Adult; Hydroxycarbamid; Hydroxycarbamide; Hypertension, Pulmonary; INCAM-110; INFLM; Image; Images, 3-D; Individual; Inducible Cell Adhesion Molecule 110; Inflammation; Insertion of catheter into heart chamber; Kidney Diseases; L-Arginine; Laboratory Research; Laser-Doppler Flowmetry; Left Ventricular Dysfunction; Leukocyte Count; Leukocyte Number; Link; Lung; Mails; Markers, Serum; Measurement; Measures; Medical; Medication; Methods; Molecular Disease; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Nephropathy; Normal Range; Normal Values; O element; O2 element; Odds Ratio; Ornithine; Oxygen; Patients; Peripheral; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacodynamics; Pharmacokinetics; Phenotype; Photography; Physiologic; Physiologic pulse; Physiological; Physiopathology; Polymorphism (Genetics); Polymorphism, Genetic; Polymorphism, Single Base; Population; Predisposition; Pressure; Pressure- physical agent; Prevalence; Prevalence Study; Prognosis; Protocol; Protocols documentation; Pulmonary Artery; Pulmonary Hypertension; Pulmonary artery structure; Pulse; Questionnaires; Regression Analyses; Regression Analysis; Regression Diagnostics; Relative Odds; Renal Disease; Research Design; Research, Laboratory; Resistance; Respiratory System, Lung; Risk Ratio; SCHED; SNP; SNPs; Schedule; Screening Result; Serum Markers; Sickle Cell; Sickle Cell Anemia; Single Nucleotide Polymorphism; Skin; Sleep; Sleep disturbances; Software; Spatial Distribution; Specific qualifier value; Specified; Statistical Regression; Study Type; Study, Prevalence; Suicidal thoughts; Susceptibility; Syndrome; System; System, LOINC Axis 4; Systolic Pressure; TBILI; TRNSF; Technology; Temperature; Testing; Therapeutic Trials; Therapy Clinical Trials; Three-Dimensional Image; Time; Total Bilirubin; Transfusion; Transthoracic Echocardiography; Urea, hydroxy-; VCAM; VCAM-1; Variant; Variation; Vascular Cell Adhesion Molecule; Vascular Cell Adhesion Molecule-1; Vasodilating Agent; Vasodilator Agents; Vasodilator Drugs; Vasodilators; Ventricular Dysfunction, Left; Visit; White Blood Cell Count procedure; adult human (21+); allelic frequency; alpha-Thalassemia; arterial tonometry; base; beta Globin; black American; cholinergic; cohort; computer program/software; depression; design; designing; disease/disorder; drepanocyte; drug/agent; enroll; follow-up; genetic analysis; genetic disorder; genetic risk factor; heart sonography; hemoglobin level; hereditary disorder; hydroxyurea; imaging; in vivo; indexing; inherited factor; interest; kidney disorder; meetings; member; outcome forecast; pathophysiology; polymorphism; pressure; pulmonary; renal disorder; resistant; response; secondary leukemia; sickle RBC; sickle cell disease; sickle disease; sickle erythrocyte; sickle red blood cell; sicklemia; sickling; sound measurement; study design; suicidal ideation; suicidal thinking; suicide ideation; thoughts about suicide; total measurement Bilirubin; treatment associated acute myelogenous leukemia; vascular
1ZIAHL006012-01 (2009): $568979
DYNAMICALLY SCALABLE ACCESSIBLE ANALYSIS FOR NEXT GENERATION SEQUENCE DATA
James Taylor
Emory University, 1599 Clifton Road, 4th Floor, Atlanta, Ga 30322
Grant 5RC2HG005542-02 from National Human Genome Research Institute
Abstract: Project Summary Wide availability of "next-generation" sequencing (NGS) instruments has enabled any investigator, for a modest cost, to produce enormous amounts of DNA sequence data. However, working with these raw sequences presents significant problems for individual investigators, small labs, or core facilities. For an experimental group with no computational expertise, simply running a data analysis program is a barrier, let alone building a compute and data storage infrastructure capable of dealing with NGS data. Fortunately, a computational model - "Cloud computing" - has recently emerged and is ideally suited to the analysis of large- scale sequence data. In this model, computation and storage exist as virtual resources, which can be dynamically allocated and released as needed. Importantly, cloud resources can provide storage and computation at far less cost than dedicated resources for certain use cases. However, formidable challenges need to be addressed to make these resources available to individual investigators. Specifically, although cloud computing provides a way to acquire computational resources on demand, the resources provided are either virtual machines on the Internet or specific programming libraries, which are unusable for experimentalists. Thus, a viable analysis solution needs to be accessible and deployable without informatics expertise; it must efficiently and automatically use dynamically scalable resources, while taking into account time and cost; it must include appropriate analysis tools and easily support addition of new tools as they emerge. We have previously developed a software system - Galaxy (http//galaxyproject.org) - that provides a robust framework for addressing these needs. Here we propose to significantly extend this framework to allow any experimentalist to perform large-scale NGS analyses utilizing the power of cloud computing infrastructure. In particular, we will modify the existing Galaxy framework to run entirely within the cloud. We will adapt the way Galaxy schedules and executes jobs to make effective use of cloud-style. We will provide a mechanism for individual users to create and deploy custom Galaxy instances on a cloud through an entirely web-based interface. Finally, we will test our approach by applying the developed facilities to the existing human re- sequencing data in order to uncover hidden patters of mutations causing human genetic disease on a very large scale. Increasingly available and inexpensive high-throughput DNA sequencing holds great promise for biomedical research, but informatics challenge block the full realization of the potential of this transformative technology. In particular progress is limited by the informatics and engineering expertise of biomedical researchers, and the availability of sufficient computational infrastructure to analyze these enormous datasets. This project will address these problems by bringing together Galaxy, a system for making complex computational analysis accessible and reproducible, with "cloud computing", an infrastructure model where computing resources are purchased on demand as needed, making it possible for investigators with no informatics expertise to perform data-intensive analysis using cloud resources
Keywords: Accounting; Address; Analysis, Data; Assay; Base Sequence; Bioassay; Biologic Assays; Biologic Sciences; Biological Assay; Biological Sciences; Biomedical Research; Cancers; Chromatin Structure; Complex; Computer Analysis; Computer Programs; Computer Simulation; Computer software; Computerized Models; Core Facility; Custom; DNA Sequence; Data; Data Analyses; Data Set; Data Storage and Retrieval; Dataset; Dependency; Dependency (Psychology); Engineering; Engineerings; Galaxy; Gene Action Regulation; Gene Expression Regulation; Gene Regulation; Gene Regulation Process; Genetic Alteration; Genetic Change; Genetic Condition; Genetic Diseases; Genetic defect; Hereditary Disease; Human; Human Genetics; Human, General; Individual; Informatics; Infrastructure; Internet; Investigators; Jobs; Large-Scale Sequencing; Libraries; Life Sciences; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Maps; Mathematical Model Simulation; Mathematical Models and Simulations; Methods and Techniques; Methods, Other; Modeling; Models, Computer; Molecular Disease; Mutation; Nucleotide Sequence; Occupations; Pattern; Professional Postions; Programs (PT); Programs [Publication Type]; Research Infrastructure; Research Personnel; Research Resources; Researchers; Resources; Running; SCHED; SEQ-AN; Schedule; Sequence Analyses; Sequence Analysis; Simulation, Computer based; Software; Solutions; System; System, LOINC Axis 4; Techniques; Technology; Testing; Time; Update; Variant; Variation; WWW; Work; computational analysis; computational modeling; computational models; computational simulation; computer based models; computer infrastructure; computer program/software; computerized modeling; computerized simulation; computing resources; cost; data retrieval; data storage; emotional dependency; genetic disorder; genome mutation; hereditary disorder; improved; in silico; instrument; malignancy; meetings; neoplasm/cancer; next generation; novel; nucleic acid sequence; programs; software systems; tool; virtual; virtual simulation; web; web based interface; world wide web
Relevance: Increasingly available and inexpensive high-throughput DNA sequencing holds great promise for biomedical research, but informatics challenge block the full realization of the potential of this transformative technology. In particular progress is limited by the informatics and engineering expertise of biomedical researchers, and the availability of sufficient computational infrastructure to analyze these enormous datasets. This project will address these problems by bringing together Galaxy, a system for making complex computational analysis accessible and reproducible, with "cloud computing", an infrastructure model where computing resources are purchased on demand as needed, making it possible for investigators with no informatics expertise to perform data-intensive analysis using cloud resources
Project start date: 2009-09-25
Project end date: 2011-07-31
Budget start date: 1-AUG-2010
Budget end date: 31-JUL-2011
PFA/PA: RFA-OD-09-004
5RC2HG005542-02 (2010): $734945
1RC2HG005542-01 (2009): $780798
A TURNKEY SOLUTION FOR NEXT GENERATION SEQUENCE DATA ANALYSIS
James Taylor
Emory University, 1599 Clifton Road, 4th Floor, Atlanta, Ga 30322
Grant 5R21HG005133-02 from National Human Genome Research Institute
Abstract: Modern biology continues to be revolutionized by high throughput data production technologies. Nowhere is this more obvious than in the case of "next-generation" DNA sequencing technologies, which have dramatically higher throughput and lower cost then previous approaches. Not only do these technologies make genome sequencing and resequencing more widely available, they have driven the development of a variety of novel genome-wide (and data-intensive) functional assays. But are these methods really accessible for experimental- ists? Although the financial cost of sequencing has been substantially reduced, there is still a significant barrier preventing experimental biologists from making effective use of this data. Translating the data generated by these new technologies requires sophisticated computational infrastructure - both for data large-scale data management and analysis - that is accessible to experimentalists. Genomic data discovery is no longer the limiting factor for much genomic research, instead the problem lies in providing the data, analysis tools, and protocols in a form that is usable for bench biologists, so that they can take full advantage of their data. We have developed a framework - Galaxy - that makes it easy to provide accessible interfaces to computational tools, and provides experimental biologists with an intuitive and consistent interface for per- forming sophisticated analyses with minimal effort, regardless of the scale of data involved. Here we propose to build, using this existing framework, a complete "turnkey" solution for accessible management and analysis of next-generation sequence data. This solution will allow data produced by sequencing instruments to be automatically made available to bench biologists through Galaxy´s user-friendly analysis environment. Into this environment we will integrate a large set of tools for sequence data analysis, along with pre-defined best- practice "workflows" for common analysis problems. The entire solution will be provided as a pre-configured ready-to-run package which any lab or provider of sequencing services can easily deploy, enabling their users to truly realize the promise of next-generation sequencing technologies. A new generation of high-throughput DNA sequencing technologies has made a variety of novel data-intensive genome-scale experiments both possible and relatively inexpensive, putting these techniques within the reach of many more labs. However, these dramatic improvements in the availability and cost of sequencing have not yet been matched with easy-to-use, scalable, integrated and flexible data analysis capabilities. The proposed project will develop an integrated data management and analysis solution that allows biomedical researchers to easily and efficiently work with the data produced by these revolutionary new technologies
Keywords: Analysis, Data; Assay; Base Sequence; Bioassay; Biologic Assays; Biological Assay; Biology; Cereals; Computer Software Tools; DNA Resequencing; DNA Sequence; Data; Data Analyses; Data Quality; Data Set; Dataset; Deposit; Deposition; Development; Ensure; Environment; Explosion; Financial cost; Galaxy; Generations; Genome; Genomics; Grain; High Performance Computing; Individual; Informatics; Institution; Intervention; Intervention Strategies; Investigators; Libraries; Maps; Metadata; Methods; Methods and Techniques; Methods, Other; Modeling; Nucleotide Sequence; One Step; One-Step dentin bonding system; Output; PROV; Production; Protocol; Protocols documentation; Provider; Quality Control; Reproducibility; Research; Research Personnel; Researchers; Resequencing; Running; Sampling; Secure; Services; Site; Software Tools; Solutions; Specific qualifier value; Specified; System; System, LOINC Axis 4; Techniques; Technology; Testing; Tools, Software; Training; Translating; Translatings; Translations; Work; computational tools; computer infrastructure; computerized tools; computing resources; cost; data management; experiment; experimental research; experimental study; feeding; flexibility; genome sequencing; genome-wide; instrument; interventional strategy; language translation; new technology; next generation; novel; nucleic acid sequence; open source; prevent; preventing; public health relevance; research study; software systems; tool; user-friendly
Relevance: A new generation of high-throughput DNA sequencing technologies has made a variety of novel data-intensive genome-scale experiments both possible and relatively inexpensive, putting these techniques within the reach of many more labs. However, these dramatic improvements in the availability and cost of sequencing have not yet been matched with easy-to-use, scalable, integrated and flexible data analysis capabilities. The proposed project will develop an integrated data management and analysis solution that allows biomedical researchers to easily and efficiently work with the data produced by these revolutionary new technologies
Project start date: 2009-07-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PAR-06-411
5R21HG005133-02 (2010): $189750
1R21HG005133-01 (2009): $255500