Biomedical subjects

Robert B Scharpf

Publications and source records attributed to Robert B Scharpf.

5 recordsLinked to original sources

PubMed2007

SNPchip: R classes and methods for SNP array data.

UNLABELLED: High-density single nucleotide polymorphism microarrays (SNP chips) provide information on a subject's genome, such as copy number and genotype (heterozygosity/homozygosity) at a SNP. While fluorescence in situ hybridization and karyotyping reveal many abnormalities, SNP chips provide a higher resolution map of the human genome that can be used to detect, e.g., aneuploidies, microdeletions, microduplications and loss of heterozygosity (LOH). As a variety of diseases are linked to such chromosomal abnormalities, SNP chips promise new insights for these diseases by aiding in the discovery of such regions, and may suggest targets for intervention. The R package SNPchip contains classes and methods useful for storing, visualizing and analyzing high density SNP data. Originally developed from the SNPscan web-tool, SNPchip utilizes S4 classes and extends other open source R tools available at Bioconductor. This has numerous advantages, including the ability to build statistical models for SNP-level data that operate on instances of the class, and to communicate with other R packages that add additional functionality. AVAILABILITY: The package is available from the Bioconductor web page at www.bioconductor.org. SUPPLEMENTARY INFORMATION: The supplementary material as described in this article (case studies, installation guidelines and R code) is available from http://biostat.jhsph.edu/~iruczins/publications/sm/

Models, Statistical↗

PubMed2006

When should one subtract background fluorescence in 2-color microarrays?

Two-color microarrays are a powerful tool for genomic analysis, but have noise components that make inferences regarding gene expression inefficient and potentially misleading. Background fluorescence, whether attributable to nonspecific binding or other sources, is an important component of noise. The decision to subtract fluorescence surrounding spots of hybridization from spot fluorescence has been controversial, with no clear criteria for determining circumstances that may favor, or disfavor, background subtraction. While it is generally accepted that subtracting background reduces bias but increases variance in the estimates of the ratios of interest, no formal analysis of the bias-variance trade off of background subtraction has been undertaken. In this paper, we use simulation to systematically examine the bias-variance trade off under a variety of possible experimental conditions. Our simulation is based on data obtained from 2 self versus self microarray experiments and is free of distributional assumptions. Our results identify factors that are important for determining whether to background subtract, including the correlation of foreground to background intensity ratios. Using these results, we develop recommendations for diagnostic visualizations that can help decisions about background subtraction.

Algorithms↗

PubMed2005

Regulation of platelet granule exocytosis by S-nitrosylation.

Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and alpha-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis.

Blood Platelets↗

PubMed2004

Platelet gene polymorphisms and cardiac risk assessment in vascular surgical patients.

BACKGROUND: Current perioperative cardiac risk assessment tools use historic and surgical factors to stratify patient risk. Polymorphisms in platelet glycoprotein (GP) IIIa and GPIbalpha are associated with myocardial ischemic risk in nonsurgical settings, but their relation to perioperative ischemia is unclear. The authors hypothesized that platelet genotype would be an independent predictor of postoperative myocardial ischemia and would improve risk assessment when added to clinical factors. METHODS: One hundred ninety-six patients who underwent infrainguinal, abdominal aortic, or thoracoabdominal vascular surgery were evaluated for clinical and genetic factors that might predict the development of postoperative myocardial ischemia. Genomic DNA was genotyped for the Leu33Pro polymorphism of GPIIIa and the Thr145Met polymorphism of GPIbalpha. Myocardial ischemic outcome was determined by review of the medical record for cardiac death or myocardial infarction and by surveillance troponin I and automated continuous 12-lead electrocardiographic analysis. RESULTS: Sixty-five patients (33%) experienced one or more ischemic endpoints (2% death, 5% myocardial infarction, 20% troponin+, 22% electrocardiogram+). The Pro33 (adjusted odds ratio [OR], 2.4 [95% confidence interval, 1.2-6.2]) and Met145 (OR 3.4 [1.4-9.3]) genotypes were independent predictors of composite ischemic outcome by multivariate regression, as were diabetes mellitus (OR 4.0 [1.7-12.5]), abdominal aortic surgery (OR 4.1 [1.7-14.4]), and thoracoabdominal aortic surgery (OR 6.4 [2.7-23.8]). The addition of platelet gene polymorphisms to clinical factors improved fit (likelihood ratio testing chi-square = 13.5, P < 0.001) of an ischemia prediction model. The derived risk assessment tool had a receiver operator characteristic curve of 0.73 (0.65-0.81) compared with 0.64 (0.57-0.74) for a model excluding genetic factors (P = 0.04). A significant relation between the GPIbalpha polymorphism and ischemic outcome remained after excluding electrocardiographic ischemia from the composite endpoint. CONCLUSIONS: Platelet polymorphisms are independent risk factors for postoperative myocardial ischemia and improve a risk prediction model when added to historic and surgical risk factors.

Aged↗

PubMed2002

Utility of whole blood hemostatometry using the clot signature analyzer for assessment of hemostasis in cardiac surgery.

BACKGROUND: A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients. METHODS: Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were also measured. RESULTS: The postprotamine CITF was greater in patients who required hemostatic transfusion than in those who did not (17.6 +/- 8.0 min vs. 10.5 +/- 5.7 min, respectively; P < 0.01). Postprotamine CITF values were highly correlated with platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed a highly significant relation between the postprotamine CITF and intraoperative platelet and fresh frozen plasma transfusion (area under the curve, 0.78-0.81, P < 0.005) with 60-80% sensitivity, specificity, positive and negative predictive values at cutoffs of 12-14 min. Logistic regression demonstrated that the CITF was independently predictive of post-CPB hemostatic transfusion, but standard hemostatic assays were not. CONCLUSIONS: The Clot Signature Analyzer CITF detects a clinical coagulopathic state after CPB and is independently predictive of the need for hemostatic transfusion. Hemostatometry has potential utility for monitoring hemostasis in cardiac surgery.

Algorithms↗