Classical and Bayesian mixed model analysis of microarray data for detecting gene expression and DNA differences

This thesis focuses on classical and Bayesian mixed model analysis of microarray data for detecting gene expression and DNA differences. It consists of three research papers. The first study discusses the selection of gene specific linear mixed models in microarray data analysis. In a microarray experiment, one experimental design is used to obtain expression measures for all genes. One popular analysis method involves fitting the same linear mixed model for each gene, obtaining gene-specific p-values for tests of interest involving fixed effects, and then choosing a threshold for significance that is intended to control False Discovery Rate (FDR) at a desired level. When one or more random factors have zero variance components for some genes, the standard practice of fitting the same full linear mixed model for all genes can result in failure to control FDR. We propose a new method which combines results from the fit of full and selected linear mixed models to identify differentially expressed genes and provide FDR control at target levels when the true underlying random effects structure varies across genes. The second study discusses a hierarchical Bayesian modeling strategy for microarray data analysis. Some microarray experiments have complex experimental designs that call for modeling of multiple sources of variation through the inclusion of multiple random factors. While large amounts of data on thousands of genes are collected in these experiments, the sample size for each gene is usually small. Therefore, in a classical gene-by-gene mixed linear model analysis, there will be very few degrees of freedom to estimate the variance components of all random factors considered in the model and low statistical power for testing fixed effects of interest. To address these challenges, we propose a hierarchical Bayesian modeling strategy to account for important experimental factors and complex correlation structure among the expression measurements for each gene. We use half-Cauchy priors for the standard deviation parameters of the random factors with few effects. We rank genes with respect to evidence of differential expression across the levels of a factor of interest by calculating a single summary statistic per gene from the posterior distribution of the treatment effects considered in the model. Simulation shows that our hierarchical Bayesian approach is much better than a traditional gene-by-gene mixed linear model analysis at distinguishing differentially expressed genes from non-differentially expressed genes. The third study focuses on the identification of Single Feature Polymorphisms (SFPs) using Affymetrix gene expression data. In microarray data analysis, the identification of SFPs is important for producing more accurate expression measurements when comparing samples of different genotypes. Also, portions of DNA that differ between parental lines can serve as markers for tracking DNA inheritance in offspring. We summarize several SFPs discovery methods in the literature. To identify single probes defining SFPs in the data, we developed two new algorithms where a difference value is defined for each probe after accounting for the overall gene expression level differences in the probe set. The first method contrast the difference value of each probe with the average of the difference values for the rest of the probes in that probe set. Second method is a robust version of the first method. The performance of all methods are compared through two publicly available published data sets, where truth about the sequence polymorphism is known for some Gold Standard probes. It was shown that our algorithms provided performance superior to the other methods in ordering probes for evidence of SFPs

Difference Covering Arrays and Pseudo-Orthogonal Latin Squares

Difference arrays are used in applications such as software testing, authentication codes and data compression. Pseudo-orthogonal Latin squares are used in experimental designs. A special class of pseudo-orthogonal Latin squares are the mutually nearly orthogonal Latin squares (MNOLS) first discussed in 2002, with general constructions given in 2007. In this paper we develop row complete MNOLS from difference covering arrays. We will use this connection to settle the spectrum question for sets of 3 mutually pseudo-orthogonal Latin squares of even order, for all but the order 146

Orthogonal trades in complete sets of MOLS

Let Bₚ be the Latin square given by the addition table for the integers modulo an odd prime p (i.e. the Cayley table for (Zₚ, +)). Here we consider the properties of Latin trades in Bₚ which preserve orthogonality with one of the p−1 MOLS given by the finite field construction. We show that for certain choices of the orthogonal mate, there is a lower bound logarithmic in p for the number of times each symbol occurs in such a trade, with an overall lower bound of (log p)² / log log p for the size of such a trade. Such trades imply the existence of orthomorphisms of the cyclic group which differ from a linear orthomorphism by a small amount. We also show that any transversal in Bₚ hits the main diagonal either p or at most p − log₂ p – 1 times. Finally, if p ≡ 1 (mod 6) we show the existence of a Latin square which is orthogonal to Bₚ and which contains a 2 × 2 subsquare

Growth performances of Shibot Fish (Tor grypus) fry fed with diets containing different protein levels

Çalışmada 2,38 g ortalama ağırlığında endemik bir tatlı su balığı olan Şabut (Tor grypus ) yavruları 3 farklı protein içerikli yemle 45 gün boyunca beslenerek büyüme performansları değerlendirilmiştir. Bu değerlendirmeleri oluşturmak amacıyla deneme grupları farklı protein seviyeli yemle beslenen G1(%33 HP), G2 (%37 HP) ve G3 (%41 HP) şeklinde kurgulanmıştır. Büyüme parametreleri olarak canlı ağırlık kazancı (CAK), Yem değerlendirme oranı (YDO), Spesifik büyüme oranı (SBO), Hayatta kalma oranı, Ekonomik dönüşüm oranı (ECR) ve Ekonomik yarar indeksi (EPI) üzerine etkileri araştırılmıştır. Yavrular araştırma sonunda sırasıyla 3,42±0,16 g, 4,17±0,06g ve 4,50±0,02 g ağırlığa ulaşmıştır. Deneme sonu FCR, EPI ve ECR açısından G3 ve G2, grubu bireyleri benzer performans göstermişlerdir.In the study, the growth performances of the Shibot fish (Tor grypus) with an average weight of 2.38 g were evaluated by feeding them with 3 different protein-containing feeds for 45 days. In order to create these evaluations, the experimental groups were designed as G1 (33%), G2 (37%) and G3 (41%) fed with different protein levels. Effects on body weight gain (BWG), Feed conversion rate (FCR), Specific growth rate (SGR), Survival rate, Economic conversion rate (ECR) and Economic profit index (EPI) as growth parameters has been researched. At the end of the study, the offspring reached a weight of 3.42±0.16 g, 4.17±0.06 g and 4.50±0.02 g, respectively. G3 and G2 group individuals showed similar performance in terms of end-trial FCR, EPI and ECR

Tasarım Eğitimi Kapsamında Monogram Logo Tasarımı

Günümüzde, iletişim ve tasarım ile oluşturulan tipografiler hayatımızın ayrılmaz bir parçası haline gelmiştir. Harfleri tasarlama ve yeni biçimler verme tasarımın hem görsel hem anlamsal değere ulaşmasını sağlamaktadır. Bu doğrultuda, harflerin temel biçimini alıp özgün ve sanatsal bir temsil yaratarak onu çarpıtmayı, stilize etmeyi veya dönüştürmeyi içermektedir. Bu araştırmada, monogram logo tasarımının tipografik soyutlama yöntemleriyle nasıl oluşturulduğunun ortaya konulması amaçlanmıştır. Bu yöntemin monogram logo tasarımı oluşturmadaki etkilerini uygulamalı olarak görebilmek amacıyla İletişim Tasarımı ve Yönetimi Bölümü’nde İletişim Tasarımı ve Yönetimine Giriş 2 dersini alan öğrenciler ile bir proje gerçekleştirilmiştir. Yapılan projede öğrenci isimlerinin baş harflerinden yola çıkarak harfler soyutlanmış ve tasarlanan biçimlerle birlikte monoram logo tasarımını oluşturma süreçleri incelenmiştir. Bu çalışma, öğrencilerin tipografik soyutlamalar konusundaki eğilimlerinin ve oluşturulan monogram logo tasarımlarının bilinçli bir şekilde yapılması açısından önemli görülmektedir. Çalışmanın sonunda; öğrencilerin somut tipografiden soyut tipografiye yönelik bir yaklaşımla monogram logo tasarımının nasıl ön plana çıktığı görülmüştür

Tasarım Eğitimi Kapsamında Monogram Logo Tasarımı

Günümüzde, iletişim ve tasarım ile oluşturulan tipografiler hayatımızın ayrılmaz bir parçası haline gelmiştir. Harfleri tasarlama ve yeni biçimler verme tasarımın hem görsel hem anlamsal değere ulaşmasını sağlamaktadır. Bu doğrultuda, harflerin temel biçimini alıp özgün ve sanatsal bir temsil yaratarak onu çarpıtmayı, stilize etmeyi veya dönüştürmeyi içermektedir. Bu araştırmada, monogram logo tasarımının tipografik soyutlama yöntemleriyle nasıl oluşturulduğunun ortaya konulması amaçlanmıştır. Bu yöntemin monogram logo tasarımı oluşturmadaki etkilerini uygulamalı olarak görebilmek amacıyla İletişim Tasarımı ve Yönetimi Bölümü’nde İletişim Tasarımı ve Yönetimine Giriş 2 dersini alan öğrenciler ile bir proje gerçekleştirilmiştir. Yapılan projede öğrenci isimlerinin baş harflerinden yola çıkarak harfler soyutlanmış ve tasarlanan biçimlerle birlikte monoram logo tasarımını oluşturma süreçleri incelenmiştir. Bu çalışma, öğrencilerin tipografik soyutlamalar konusundaki eğilimlerinin ve oluşturulan monogram logo tasarımlarının bilinçli bir şekilde yapılması açısından önemli görülmektedir. Çalışmanın sonunda; öğrencilerin somut tipografiden soyut tipografiye yönelik bir yaklaşımla monogram logo tasarımının nasıl ön plana çıktığı görülmüştür

Anti-Pasch optimal coverings with triples

It is shown that for $v\ne 7,8,11,12$ or $13$, there exists an optimal covering with triples on $v$ points that contains no Pasch configurations

Gene expression in intestinal mucosal biopsy specimens obtained from dogs with chronic enteropathy

Objective—To characterize mucosal gene expression in dogs with chronic enteropathy (CE). Animals—18 dogs with CE and 6 healthy control dogs. Procedures—Small intestinal mucosal biopsy specimens were endoscopically obtained from dogs. Disease severity in dogs with CE was determined via inflammatory bowel index scores and histologic grading of biopsy specimens. Total RNA was extracted from biopsy specimens and microchip array analysis (approx 43,000 probe sets) and quantitative reverse transcriptase PCR assays were performed. Results—1,875 genes were differentially expressed between dogs with CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with CE, including neurotensin, fatty acid–binding protein 6, fatty acid synthase, aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8, whereas few genes were upregulated in dogs with CE, including genes encoding products involved in extracellular matrix degradation (matrix metallopeptidases 1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome proliferator–activated receptor γ, and S100 calcium-binding protein G), iron transport (solute carrier family 40 member 1), and immunity (CD96 and carcinoembryonic antigen–related cell adhesion molecule [CEACAM] 18). Dogs with CE and protein-losing enteropathy had the greatest number of differentially expressed genes. Results of quantitative reverse transcriptase PCR assay for select genes were similar to those for microchip array analysis. Conclusions and Clinical Relevance—Expression of genes encoding products regulating mucosal inflammation was altered in dogs with CE and varied with disease severity. Impact for Human Medicine—Molecular pathogenesis of CE in dogs may be similar to that in humans with inflammatory bowel disease