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

Academic drift in vocational qualifications? Explorations through the lens of literacy

Retention, attainment and progression have become key issues in post-compulsory education in the UK, as the policy agenda of increasing and widening participation has taken hold. Keeping students in the system, enabling them to gain qualifications and thereby progress to higher level courses is a key educational goal. Yet alongside increasing progression and attainment have emerged discussion of the nature and extent of academic drift within vocational education. This paper seeks to explore these issues in the context of the vocational curriculum in Further Education colleges in Scotland. Using the lens of literacy practices, we explore the ways in which the expectations upon students of the reading and writing associated with learning their subjects can illuminate the nature and extent of academic drift. We indicate evidence to suggest that there is increasing emphasis given to educational rather than occupational relevance in the vocational curriculu

Teachers' classroom feedback: still trying to get it right

This article examines feedback traditionally given by teachers in schools. Such feedback tends to focus on children's acquisition and retrieval of externally prescribed knowledge which is then assessed against mandated tests. It suggests that, from a sociocultural learning perspective, feedback directed towards such objectives may limit children's social development. In this article, I draw on observation and interview data gathered from a group of 27 9- to 10-year olds in a UK primary school. These data illustrate the children's perceived need to conform to, rather than negotiate, the teacher's feedback comments. They highlight the children's sense that the teacher's feedback relates to school learning but not to their own interests. The article also includes alternative examples of feedback which draw on children's own inquiries and which relate to the social contexts within which, and for whom, they act. It concludes by suggesting that instead of looking for the right answer to the question of what makes teachers' feedback effective in our current classrooms, a more productive question might be how a negotiation can be opened up among teachers and learners themselves, about how teachers' feedback could support children's learning most appropriately

Genetic by environmental variation but no local adaptation in oysters ( Crassostrea virginica )

Functional trait variation within and across populations can strongly influence population, community, and ecosystem processes, but the relative contributions of genetic vs. environmental factors to this variation are often not clear, potentially complicating conservation and restoration efforts. For example, local adaptation, a particular type of genetic by environmental (G*E) interaction in which the fitness of a population in its own habitat is greater than in other habitats, is often invoked in management practices, even in the absence of supporting evidence. Despite increasing attention to the potential for G*E interactions, few studies have tested multiple populations and environments simultaneously, limiting our understanding of the spatial consistency in patterns of adaptive genetic variation. In addition, few studies explicitly differentiate adaptation in response to predation from other biological and environmental factors. We conducted a reciprocal transplant experiment of first-generation eastern oyster (Crassostrea virginica) juveniles from six populations across three field sites spanning 1000 km in the southeastern Atlantic Bight in both the presence and absence of predation to test for G*E variation in this economically valuable and ecologically important species. We documented significant G*E variation in survival and growth, yet there was no evidence for local adaptation. Condition varied across oyster cohorts: Offspring of northern populations had better condition than offspring from the center of our region. Oyster populations in the southeastern Atlantic Bight differ in juvenile survival, growth, and condition, yet offspring from local broodstock do not have higher survival or growth than those from farther away. In the absence of population-specific performance information, oyster restoration and aquaculture may benefit from incorporating multiple populations into their practices

The significance of motivation in student-centred learning : a reflective case study

The theoretical underpinnings of student-centred learning suggest motivation to be an integral component. However, lack of clarification of what is involved in motivation in education often results in unchallenged assumptions that fail to recognise that what motivates some students may alienate others. This case study, using socio-cognitive motivational theory to analyse previously collected data, derives three fuzzy propositions which, collectively, suggest that motivation interacts with the whole cycle of episodes in the teachinglearning process. It argues that the development of the higherlevel cognitive competencies that are implied by the term, student-centred learning, must integrate motivational constructs such as goal orientation, volition, interest and attributions into pedagogical practices

Levels and equivalence in credit and qualifications frameworks: Contrasting the prescribed and enacted curriculum in school and college

Drawing on data from an empirical study of three matched subjects in upper secondary school and further education college in Scotland, this article explores some of the factors that result in differences emerging from the translation of the prescribed curriculum into the enacted curriculum. We argue that these differences raise important questions about equivalences which are being promoted through the development of credit and qualifications frameworks. The article suggests that the standardisation associated with the development of a rational credit and qualifications framework and an outcomes-based prescribed curriculum cannot be achieved precisely because of the multiplicity that emerges from the practices of translation

A high-quality genome and comparison of short- versus long-read transcriptome of the palaearctic duck Aythya fuligula (tufted duck)

Background: The tufted duck is a non-model organism that experiences high mortality in highly pathogenic avian influenza outbreaks. It belongs to the same bird family (Anatidae) as the mallard, one of the best-studied natural hosts of low-pathogenic avian influenza viruses. Studies in non-model bird species are crucial to disentangle the role of the host response in avian influenza virus infection in the natural reservoir. Such endeavour requires a high-quality genome assembly and transcriptome. Findings: This study presents the first high-quality, chromosome-level reference genome assembly of the tufted duck using the Vertebrate Genomes Project pipeline. We sequenced RNA (complementary DNA) from brain, ileum, lung, ovary, spleen, and testis using Illumina short-read and Pacific Biosciences long-read sequencing platforms, which were used for annotation. We found 34 autosomes plus Z and W sex chromosomes in the curated genome assembly, with 99.6% of the sequence assigned to chromosomes. Functional annotation revealed 14,099 protein-coding genes that generate 111,934 transcripts, which implies a mean of 7.9 isoforms per gene. We also identified 246 small RNA families. Conclusions: This annotated genome contributes to continuing research into the host response in avian influenza virus infections in a natural reservoir. Our findings from a comparison between short-read and long -read reference transcriptomics contribute to a deeper understanding of these competing options. In this study, both technologies complemented each other. We expect this annotation to be a foundation for further comparative and evolutionary genomic studies, including many waterfowl relatives with differing susceptibilities to avian influenza viruses

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management