SIMAGE: SImulation of DNA-MicroArray Gene Expression data

Background: Simulation of DNA-microarray data serves at least three purposes: (i) optimizing the design of an intended DNA microarray experiment, (ii) comparing existing pre-processing and processing methods for best analysis of a given DNA microarray experiment, (iii) educating students, lab-workers and other researchers by making them aware of the many factors influencing DNA microarray experiments. Results: Our model has multiple layers of factors influencing the experiment. The relative influence of such factors can differ significantly between labs, experiments within labs, etc. Therefore, we have added a module to roughly estimate their parameters from a given data set. This guarantees that our simulated data mimics real data as closely as possible. Conclusions: We introduce a model for the simulation of dual-dye cDNA-microarray data closely resembling real data and coin the model and its software implementation SIMAGE which stands for simulation of microarray gene expression data. The software is freely accessible at: http://bioinformatics.biol.rug.nl/websoftware/simag

Association testing by haplotype-sharing methods applicable to whole-genome analysis

We propose two new haplotype-sharing methods for identifying disease loci: the haplotype sharing statistic (HSS), which compares length of shared haplotypes between cases and controls, and the CROSS test, which tests whether a case and a control haplotype show less sharing than two random haplotypes. The significance of the HSS is determined using a variance estimate from the theory of U-statistics, whereas the significance of the CROSS test is estimated from a sequential randomization procedure. Both methods are fast and hence practical, even for whole-genome screens with high marker densities. We analyzed data sets of Problems 2 and 3 of Genetic Analysis Workshop 15 and compared HSS and CROSS to conventional association methods. Problem 2 provided a data set of 2300 single-nucleotide polymorphisms (SNPs) in a 10-Mb region of chromosome 18q, which had shown linkage evidence for rheumatoid arthritis. The CROSS test detected a significant association at approximately position 4407 kb. This was supported by single-marker association and HSS. The CROSS test outperformed them both with respect to significance level and signal-to-noise ratio. A 20-kb candidate region could be identified. Problem 3 provided a simulated 10 k SNP data set covering the whole genome. Three known candidate regions for rheumatoid arthritis were detected. Again, the CROSS test gave the most significant results. Furthermore, both the HSS and the CROSS showed better fine-mapping accuracy than straightforward haplotype association. In conclusion, haplotype sharing methods, particularly the CROSS test, show great promise for identifying disease gene loci

A view from the clinic – Perspectives from Dutch patients and professionals on high myopia care

Purpose: To understand and compare perspectives of patients and professionals on current ophthalmologic care for high myopia, and to identify challenges and future opportunities. Methods: Self-reported data were collected through two online questionnaires. Patient perspective was obtained from highly myopic members of a patient organisation based in the Netherlands using a 17-item questionnaire consisting of open and multiple-choice questions regarding personal experience with myopia care. The ophthalmologist perspective was obtained from practising Dutch ophthalmologists with a 12-item questionnaire of multiple-choice questions on work-related demographics, myopia care in daily practice and need for improvement. The response rate for patients was 27% (n = 136/500) and for ophthalmologists, 24% (n = 169/716). Results: Patients were highly concerned about personal progressive loss of vision (69%) and feared their psychological well-being (82%) in case this would happen. The quality of performance of care provided by ophthalmologists was rated as excellent or satisfactory by 64% of the patients. These ratings for multidisciplinary care and insurance reimbursement were as low as 28% and 18% respectively. The mean concern among ophthalmologists about the rise in high myopia was 6.9 (SEM 0.1) on a 10-point scale. Sixty-nine per cent of the ophthalmologists reported that asymptomatic myopic patients should not be examined regularly at outpatient clinics. Ophthalmologists urged the development of clinical guidelines (74%), but did report (95%) that they informed patients about risk factors and complications. This contrasted with the view of patients, of whom 42% were discontent with information provided by ophthalmologists. Conclusions: These questionnaires demonstrated that the current clinical care delivered to highly myopic patients is in need of improvement. The expected higher demand for myopia care in the near future requires preferred practice patterns, professionals specifically trained to manage myopic pathology, accurate and comprehensive information exchange and collaboration of in- and out-of-hospital professionals across the full eye care chain.</p

Genetical genomics: spotlight on QTL hotspots

No abstract available