caCORRECT2: Improving the accuracy and reliability of microarray data in the presence of artifacts

© 2011 Moffitt et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.DOI: 10.1186/1471-2105-12-383Background. In previous work, we reported the development of caCORRECT, a novel microarray quality control system built to identify and correct spatial artifacts commonly found on Affymetrix arrays. We have made recent improvements to caCORRECT, including the development of a model-based data-replacement strategy and integration with typical microarray workflows via caCORRECT's web portal and caBIG grid services. In this report, we demonstrate that caCORRECT improves the reproducibility and reliability of experimental results across several common Affymetrix microarray platforms. caCORRECT represents an advance over state-of-art quality control methods such as Harshlighting, and acts to improve gene expression calculation techniques such as PLIER, RMA and MAS5.0, because it incorporates spatial information into outlier detection as well as outlier information into probe normalization. The ability of caCORRECT to recover accurate gene expressions from low quality probe intensity data is assessed using a combination of real and synthetic artifacts with PCR follow-up confirmation and the affycomp spike in data. The caCORRECT tool can be accessed at the website: http://cacorrect.bme.gatech.edu webcite. Results. We demonstrate that (1) caCORRECT's artifact-aware normalization avoids the undesirable global data warping that happens when any damaged chips are processed without caCORRECT; (2) When used upstream of RMA, PLIER, or MAS5.0, the data imputation of caCORRECT generally improves the accuracy of microarray gene expression in the presence of artifacts more than using Harshlighting or not using any quality control; (3) Biomarkers selected from artifactual microarray data which have undergone the quality control procedures of caCORRECT are more likely to be reliable, as shown by both spike in and PCR validation experiments. Finally, we present a case study of the use of caCORRECT to reliably identify biomarkers for renal cell carcinoma, yielding two diagnostic biomarkers with potential clinical utility, PRKAB1 and NNMT. Conclusions. caCORRECT is shown to improve the accuracy of gene expression, and the reproducibility of experimental results in clinical application. This study suggests that caCORRECT will be useful to clean up possible artifacts in new as well as archived microarray data

Hectospec, the MMT's 300 Optical Fiber-Fed Spectrograph

The Hectospec is a 300 optical fiber fed spectrograph commissioned at the MMT in the spring of 2004. A pair of high-speed six-axis robots move the 300 fiber buttons between observing configurations within ~300 s and to an accuracy ~25 microns. The optical fibers run for 26 m between the MMT's focal surface and the bench spectrograph operating at R~1000-2000. Another high dispersion bench spectrograph offering R~5,000, Hectochelle, is also available. The system throughput, including all losses in the telescope optics, fibers, and spectrograph peaks at ~10% at the grating blaze in 1" FWHM seeing. Correcting for aperture losses at the 1.5" diameter fiber entrance aperture, the system throughput peaks at $\sim$17%. Hectospec has proven to be a workhorse instrument at the MMT. Hectospec and Hectochelle together were scheduled for 1/3 of the available nights since its commissioning. Hectospec has returned \~60,000 reduced spectra for 16 scientific programs during its first year of operation.Comment: 68 pages, 28 figures, to appear in December 2005 PAS

The Effect of Sample Handling on Cross Sectional HIV Incidence Testing Results

To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays.Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4 °C, 25 °C and 37 °C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay).Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4 °C or 25 °C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37 °C prior to testing.Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4 °C or 25 °C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37°C for three or more days did affect results obtained with these assays

Crop Water Stress Index of an Irrigated Vineyard in the Central Valley of California

Water-limiting conditions in many California vineyards necessitate assessment of vine water stress to aid irrigation management strategies and decisions. This study was designed to evaluate the utility of a Crop Water Stress Index (CWSI) using multiple canopy temperature sensors and to study the diurnal signature in the stress index of an irrigated vineyard. A detailed instrumentation package comprised of eddy covariance instrumentation, ancillary surface energy balance components, soil water content sensors and a unique multi-canopy temperature sensor array were deployed in a production vineyard near Lodi, CA. The instrument package was designed to measure and monitor hourly growing season turbulent fluxes of heat and water vapor, radiation, air temperature, soil water content directly beneath a vine canopy, and vine canopy temperatures. April 30–May 02, June 10–12 and July 27–28, 2016 were selected for analysis as these periods represented key vine growth and production phases. Considerable variation in computed CWSI was observed between each of the hourly average individual canopy temperature sensors throughout the study; however, the diurnal trends remained similar: highest CWSI values in morning and lowest in the late afternoon. While meteorological conditions were favorable for plant stress to develop, soil water content near field capacity due to frequent irrigation allowed high evapotranspiration rates resulting in downward trending CWSI values during peak evaporative demand. While the CWSI is typically used to evaluate plant stress under the conditions of our study, the trend of the CWSI suggested a lowering of plant water stress as long as there was adequate soil water available to meet atmospheric demand

Crafting Critical Heritage Discourses into Interactive Exhibition Design

This paper argues how a more reflective design practice that embraces critical discourses can transform interactive exhibition design and therefore the museum visiting experience. Four framing arguments underpin our exhibition design making: the value of materiality, visiting as an aesthetic experience, challenging the authorized voice, and heritage as a process. These arguments were embodied through design, art and craft practice into one interactive exhibition at a house museum. We draw from our design process discussing the implications that adopting an approach informed by critical heritage debates has on exhibition design and suggest three sensitizing concepts (polyvocal narratives, dialogical interaction, interweaving time and space) bridging the practice of interactive exhibition design and critical heritage theory

Coronary Computed Tomography Angiography for Early Triage of Patients With Acute Chest Pain The ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) Trial

ObjectivesThis study was designed to determine the usefulness of coronary computed tomography angiography (CTA) in patients with acute chest pain.BackgroundTriage of chest pain patients in the emergency department remains challenging.MethodsWe used an observational cohort study in chest pain patients with normal initial troponin and nonischemic electrocardiogram. A 64-slice coronary CTA was performed before admission to detect coronary plaque and stenosis (>50% luminal narrowing). Results were not disclosed. End points were acute coronary syndrome (ACS) during index hospitalization and major adverse cardiac events during 6-month follow-up.ResultsAmong 368 patients (mean age 53 ± 12 years, 61% men), 31 had ACS (8%). By coronary CTA, 50% of these patients were free of coronary artery disease (CAD), 31% had nonobstructive disease, and 19% had inconclusive or positive computed tomography for significant stenosis. Sensitivity and negative predictive value for ACS were 100% (n = 183 of 368; 95% confidence interval [CI]: 98% to 100%) and 100% (95% CI: 89% to 100%), respectively, with the absence of CAD and 77% (95% CI: 59% to 90%) and 98% (n = 300 of 368, 95% CI: 95% to 99%), respectively, with significant stenosis by coronary CTA. Specificity of presence of plaque and stenosis for ACS were 54% (95% CI: 49% to 60%) and 87% (95% CI: 83% to 90%), respectively. Only 1 ACS occurred in the absence of calcified plaque. Both the extent of coronary plaque and presence of stenosis predicted ACS independently and incrementally to Thrombolysis In Myocardial Infarction risk score (area under curve: 0.88, 0.82, vs. 0.63, respectively; all p < 0.0001).ConclusionsFifty percent of patients with acute chest pain and low to intermediate likelihood of ACS were free of CAD by computed tomography and had no ACS. Given the large number of such patients, early coronary CTA may significantly improve patient management in the emergency department

Risk factors for the development of severe typhoid fever in Vietnam

Background Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever. Methods We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993–1995 and 1997–1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission. Results The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00-2.57; p = 0.035). Conclusions In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was independently associated with disease severity. During this period many patients were being treated with fluoroquinolones prior to hospital admission. Ciprofloxacin and ofloxacin should be used with caution in patients infected with S. Typhi that have intermediate susceptibility to ciprofloxacin

Meta-analyses of the sensitivity and specificity of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis in the UK and Ireland

Publication history: Accepted - 26 February 2017; Published online - 6th March 2017.Bovine Tuberculosis (bTB) in cattle is a global health problem and eradication of the disease requires accu-rate estimates of diagnostic test performance to optimize their efficiency. The objective of this study was,through statistical meta-analyses, to obtain estimates of sensitivity (Se) and specificity (Sp), for 14 differ-ent ante-mortem and post-mortem diagnostic tests for bTB in cattle. Using data from a systematic reviewof the scientific literature (published 1934–2009) diagnostic Se and Sp were estimated using Bayesianlogistic regression models adjusting for confounding factors. Random effect terms were used to accountfor unexplained heterogeneity. Parameters in the models were implemented using Markov Chain MonteCarlo (MCMC), and posterior distributions for the diagnostic parameters with adjustment for covariates(confounding factors) were obtained using the inverse logit function. Estimates for Se and/or Sp of thetuberculin skin tests and the IFN- blood test were compared with estimates published 2010–2015.Median Se for the single intradermal comparative cervical tuberculin skin (SICCT) test (standard inter-pretation) was 0.50 and Bayesian credible intervals (CrI) were wide (95% CrI 0.26, 0.78). Median Sp forthe SICCT test was 1.00 (95% CrI 0.99, 1.00). Estimates for the IFN- blood test Bovine Purified ProteinDerivative (PPD)-Avian PPD and Early Secreted Antigen target 6 and Culture Filtrate Protein 10 (ESAT-6/CFP10) ESAT6/CFP10 were 0.67 (95% CrI 0.49, 0.82) and 0.78 (95% CrI 0.60, 0.90) respectively for Se,and 0.98 (95% CrI 0.96, 0.99) and 0.99 (95% CrI 0.99, 1.00) for Sp. The study provides an overview of theaccuracy of a range of contemporary diagnostic tests for bTB in cattle. Better understanding of diagnostictest performance is essential for the design of effective control strategies and their evaluation.The SE3238 project “Meta-analysis of diagnostic tests and modelling to identify appropriate testing strategies to reduce M. bovis infection in GB herds” was funded by the UK Department for Envi-ronment, Food and Rural Affairs (Defra)