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In recent years, there has been a renewed interest in applying statistical ranking criteria to identify sites on a road network, which potentially present high traffic crash risks or are over-represented in certain type of crashes, for further engineering evaluation and safety improvement. This requires that good estimates of ranks of crash risks be obtained at individual intersections or road segments, or some analysis zones. The nature of this site ranking problem in roadway safety is related to two well-established statistical problems known as the small area (or domain) estimation problem and the disease mapping problem. The former arises in the context of providing estimates using sample survey data for a small geographical area or a small socio-demographic group in a large area, while the latter stems from estimating rare disease incidences for typically small geographical areas. The statistical problem is such that direct estimates of certain parameters associated with a site (or a group of sites) with adequate precision cannot be produced, due to a small available sample size, the rareness of the event of interest, and/or a small exposed population or sub-population in question. Model based approaches have offered several advantages to these estimation problems, including increased precision by "borrowing strengths" across the various sites based on available auxiliary variables, including their relative locations in space. Within the model based approach, generalized linear mixed models (GLMM) have played key roles in addressing these problems for many years. The objective of the study, on which this paper is based, was to explore some of the issues raised in recent roadway safety studies regarding ranking methodologies in light of the recent statistical development in space-time GLMM. First, general ranking approaches are reviewed, which include naïve or raw crash-risk ranking, scan based ranking, and model based ranking. Through simulations, the limitation of using the naïve approach in ranking is illustrated. Second, following the model based approach, the choice of decision parameters and consideration of treatability are discussed. Third, several statistical ranking criteria that have been used in biomedical, health, and other scientific studies are presented from a Bayesian perspective. Their applications in roadway safety are then demonstrated using two data sets: one for individual urban intersections and one for rural two-lane roads at the county level. As part of the demonstration, it is shown how multivariate spatial GLMM can be used to model traffic crashes of several injury severity types simultaneously and how the model can be used within a Bayesian framework to rank sites by crash cost per vehicle-mile traveled (instead of by crash frequency rate). Finally, the significant impact of spatial effects on the overall model goodness-of-fit and site ranking performances are discussed for the two data sets examined. The paper is concluded with a discussion on possible directions in which the study can be extended.

Background Infection by infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) causes acute respiratory diseases in chickens often with high mortality. To better understand host-ILTV interactions at the host transcriptional level, a microarray analysis was performed using 4 × 44 K Agilent chicken custom oligo microarrays. Results Microarrays were hybridized using the two color hybridization method with total RNA extracted from ILTV infected chicken embryo lung cells at 0, 1, 3, 5, and 7 days post infection (dpi). Results showed that 789 genes were differentially expressed in response to ILTV infection that include genes involved in the immune system (cytokines, chemokines, MHC, and NF-κB), cell cycle regulation (cyclin B2, CDK1, and CKI3), matrix metalloproteinases (MMPs) and cellular metabolism. Differential expression for 20 out of 789 genes were confirmed by quantitative reverse transcription-PCR (qRT-PCR). A bioinformatics tool (Ingenuity Pathway Analysis) used to analyze biological functions and pathways on the group of 789 differentially expressed genes revealed that 21 possible gene networks with intermolecular connections among 275 functionally identified genes. These 275 genes were classified into a number of functional groups that included cancer, genetic disorder, cellular growth and proliferation, and cell death. Conclusion The results of this study provide comprehensive knowledge on global gene expression, and biological functionalities of differentially expressed genes in chicken embryo lung cells in response to ILTV infections.

Microarray is one of the most powerful DNA detection systems with multiplexing and high throughput capability. However, the current application of microarray is limited to the preliminary genomic screening of biological samples despite of its excellent potentials for other applications, such as biosensing. This paper addresses microarray's possibilities as sensing device by investigating its limit of detection (LOD) and limit of quantification (LOQ), which are defined as the minimum fluorophore concentration for the liable signal detection. The LOD and LOQ, i.e., detection sensitivity, are key indexes to determine the microarray's applicability as bio/nano sensing device.

The value of accurate weather forecast information is substantial. In this paper we examine competition among forecast providers and its implications for the quality of forecasts. A simple economic model shows that an economic bias geographical inequality in forecast accuracy arises due to the extent of the market. Using the unique data on daily high temperature forecasts for 704 U.S. cities, we find that forecast accuracy increases with population and income. Furthermore, the economic bias gets larger when the day of forecasting is closer to the target day; i.e. when people are more concerned about the quality of forecasts. The results hold even after we control for location-specific heterogeneity and difficulty of forecasting.

In recent years there has been an increased interest in using protein mass spectroscopy to discriminate diseased from healthy individuals with the aim of discovering molecular markers for disease. A crucial step before any statistical analysis is the pre-processing of the mass spectrometry data. Statistical results are typically strongly affected by the specific pre-processing techniques used. One important pre-processing step is the removal of chemical and instrumental noise from the mass spectra. Wavelet denoising techniques are a standard method for denoising. Existing techniques, however, do not accommodate errors that vary across the mass spectrum, but instead assume a homogeneous error structure. In this paper we propose a novel wavelet denoising approach that deals with heterogeneous errors by incorporating a variance change point detection method in the thresholding procedure. We study our method on real and simulated mass spectrometry data and show that it improves on performances of peak detection methods.

Estimation of reliability and maintainability parameters is essential in modeling repairable systems and determining maintenance policies. However, because of the aging of repairable systems under imperfect maintenance, failure times are neither identically nor independently distributed, which makes parameter estimation difficult. In this paper, we apply Bayesian methods for estimation of reliability and maintainability parameters based on historical reliability and maintainability (RAM) data. We assume the first failure of the repairable system follows a Weibull probability distribution. The repairable system experiences Kijima Type I imperfect corrective maintenance and Kijima Type I imperfect preventive maintenance. Using a Bayesian perspective, we estimate four parameters for this repairable system: the shape parameter of the Weibull probability distribution (beta), the scale parameter of the Weibull distribution (eta), the imperfect maintenance factor for corrective maintenance (alphar) and the imperfect maintenance factor for preventive maintenance (alphap). The proposed method is illustrated with simulated RAM data.

Classification problems have received considerable attention in biological and medical applications. In particular, classification methods combining to microarray technology play an important role in diagnosing and predicting disease, such as cancer, in medical research. Primary objective in classification is to build an optimal classifier based on the training sample in order to predict unknown class in the test sample. In this paper, we propose a unified approach for optimal gene classification with conjunction with functional principal component analysis (FPCA) in functional data analysis (FNDA) framework to classify time-course gene expression profiles based on information from the patterns. To derive an optimal classifier in FNDA, we also propose to find optimal number of bases in the smoothing step and functional principal components in FPCA using a cross-validation technique, and compare the performance of some popular classification techniques in the proposed setting. We illustrate the propose method with a simulation study and a real world data analysis.

Clustering of gene expression data collected across time is receiving growing attention in the biological literature since time-course experiments allow one to understand dynamic biological processes and identify genes governed by the same processes. It is believed that genes demonstrating similar expression profiles over time might give an informative insight into how underlying biological mechanisms work. In this paper, we propose a method based on functional data analysis (FNDA) to cluster time-dependent gene expression profiles. Consideration of clustering problems using the FNDA setting provides ways to take time dependency into account by using basis function expansion to describe the partially observed curves. We also discuss how to choose the number of bases in the basis function expansion in FNDA. A synthetic cycle data and a real data are used to demonstrate the proposed method and some comparisons between the proposed and existing approaches using the adjusted Rand indices are made.

Background Biologists often conduct multiple but different cDNA microarray studies that all target the same biological system or pathway. Within each study, replicate slides within repeated identical experiments are often produced. Pooling information across studies can help more accurately identify true target genes. Here, we introduce a method to integrate multiple independent studies efficiently. Results We introduce a Bayesian hierarchical model to pool cDNA microarray data across multiple independent studies to identify highly expressed genes. Each study has multiple sources of variation, i.e. replicate slides within repeated identical experiments. Our model produces the gene-specific posterior probability of differential expression, which provides a direct method for ranking genes, and provides Bayesian estimates of false discovery rates (FDR). In simulations combining two and five independent studies, with fixed FDR levels, we observed large increases in the number of discovered genes in pooled versus individual analyses. When the number of output genes is fixed (e.g., top 100), the pooled model found appreciably more truly differentially expressed genes than the individual studies. We were also able to identify more differentially expressed genes from pooling two independent studies in Bacillus subtilis than from each individual data set. Finally, we observed that in our simulation studies our Bayesian FDR estimates tracked the true FDRs very well. Conclusion Our method provides a cohesive framework for combining multiple but not identical microarray studies with several sources of replication, with data produced from the same platform. We assume that each study contains only two conditions: an experimental and a control sample. We demonstrated our model's suitability for a small number of studies that have been either pre-scaled or have no outliers.

The Smyth line (SL) chicken is an animal model for autoimmune vitiligo (SLV). SL chickens develop spontaneous, post-hatch, autoimmune melanocyte loss in growing feathers (GF). With repeatable access to GF and the high incidence (85-95%) of SLV, SLV development can be examined in the same bird. A microarray study was conducted to investigate the global transcriptomic profile in GF from SL and Brown line (BL, parental control) chickens. RNA pools were made from GF of BL chickens, SL chickens that never developed SLV (S0), and SL chickens before (S1), during (S2) and at complete (S3) SLV. Complementary RNA probes were generated from BL and SL (S0~S3) RNA, labeled with Cy3 and Cy5, respectively and hybridized on a chicken 4x44 K Agilent microarray. The slide was scanned and normalized signal intensities were analyzed to identify differentially expressed (DE, >2x) genes between BL and SL samples. There were 504, 518, 1124, and 1151 DE genes containing 262, 226, 658, and 680 unique DE genes in S0, S1, S2 and S3, respectively. S0 and S1 had similar proportions of up-and down-regulated DE genes while up-regulated DE genes predominated in S2 and S3. The highest expressed DE genes were related to immune activity and cell death. Ingenuity Pathway Analysis software was used to determine biological functions and pathways of DE genes. The study provides comprehensive information from global gene expression to functionalities and biological networks of DE genes in the process of SLV.

Background With the growing abundance of microarray data, statistical methods are increasingly needed to integrate results across studies. Two common approaches for meta-analysis of microarrays include either combining gene expression measures across studies or combining summaries such as p-values, probabilities or ranks. Here, we compare two Bayesian meta-analysis models that are analogous to these methods. Results Two Bayesian meta-analysis models for microarray data have recently been introduced. The first model combines standardized gene expression measures across studies into an overall mean, accounting for inter-study variability, while the second combines probabilities of differential expression without combining expression values. Both models produce the gene-specific posterior probability of differential expression, which is the basis for inference. Since the standardized expression integration model includes inter-study variability, it may improve accuracy of results versus the probability integration model. However, due to the small number of studies typical in microarray meta-analyses, the variability between studies is challenging to estimate. The probability integration model eliminates the need to model variability between studies, and thus its implementation is more straightforward. We found in simulations of two and five studies that combining probabilities outperformed combining standardized gene expression measures for three comparison values: the percent of true discovered genes in meta-analysis versus individual studies; the percent of true genes omitted in meta-analysis versus separate studies, and the number of true discovered genes for fixed levels of Bayesian false discovery. We identified similar results when pooling two independent studies of Bacillus subtilis. We assumed that each study was produced from the same microarray platform with only two conditions: a treatment and control, and that the data sets were pre-scaled. Conclusion The Bayesian meta-analysis model that combines probabilities across studies does not aggregate gene expression measures, thus an inter-study variability parameter is not included in the model. This results in a simpler modeling approach than aggregating expression measures, which accounts for variability across studies. The probability integration model identified more true discovered genes and fewer true omitted genes than combining expression measures, for our data sets.

Background The Smyth line (SL) of chicken is an excellent avian model for human autoimmune vitiligo. The etiology of vitiligo is complicated and far from clear. In order to better understand critical components leading to vitiligo development, cDNA microarray technology was used to compare gene expression profiles in the target tissue (the growing feather) of SL chickens at different vitiligo (SLV) states. Results Compared to the reference sample, which was from Brown line chickens (the parental control), 395, 522, 524 and 526 out of the 44 k genes were differentially expressed (DE) (P ≤ 0.05) in feather samples collected from SL chickens that never developed SLV (NV), from SLV chickens prior to SLV onset (EV), during active loss of pigmentation (AV), and after complete loss of melanocytes (CV). Comparisons of gene expression levels within SL samples (NV, EV, AV and CV) revealed 206 DE genes, which could be categorized into immune system-, melanocyte-, stress-, and apoptosis-related genes based on the biological functions of their corresponding proteins. The autoimmune nature of SLV was supported by predominant presence of immune system related DE genes and their remarkably elevated expression in AV samples compared to NV, EV and/or CV samples. Melanocyte loss was confirmed by decreased expression of genes for melanocyte related proteins in AV and CV samples compared to NV and EV samples. In addition, SLV development was also accompanied by altered expression of genes associated with disturbed redox status and apoptosis. Ingenuity Pathway Analysis of DE genes provided functional interpretations involving but not limited to innate and adaptive immune response, oxidative stress and cell death. Conclusions The microarray results provided comprehensive information at the transcriptome level supporting the multifactorial etiology of vitiligo, where together with apparent inflammatory/innate immune activity and oxidative stress, the adaptive immune response plays a predominant role in melanocyte loss.

The detection of gene-gene interaction is an important approach to understand the etiology of rheumatoid arthritis (RA). The goal of this study is to identify gene-gene interaction of SNPs at the allelic level contributing to RA using real data sets (Problem 1) of North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Analysis Workshop 16 (GAW16). We applied our novel method that can detect the interaction by a definition of nonrandom association of alleles that occurs when the contribution to RA of a particular allele inherited in one gene depends on a particular allele inherited at other unlinked genes. Starting with 639 single-nucleotide polymorphisms (SNPs) from 26 candidate genes, we identified ten two-way interacting genes and one case of three-way interacting genes. SNP rs2476601 on PTPN22 interacts with rs2306772 on SLC22A4, which interacts with rs881372 on TRAF1 and rs2900180 on C5, respectively. SNP rs2900180 on C5 interacts with rs2242720 on RUNX1, which interacts with rs881375 on TRAF1. Furthermore, rs2476601 on PTPN22 also interacts with three SNPs (rs2905325, rs1476482, and rs2106549) in linkage disequilibrium (LD) on IL6. The other three SNPs (rs2961280, rs2961283, and rs2905308) in LD on IL6 interact with two SNPs (rs477515 and rs2516049) on HLA-DRB1. SNPs rs660895 and rs532098 on HLA-DRB1 interact with rs2834779 and four SNPs in LD on RUNX1. Three-way interacting genes of rs10229203 on IL6, rs4816502 on RUNX1, and rs10818500 on C5 were also detected.