Mouse anti-Human KAP monoclonal antibody, clone 40/LBQ

Time-course microarray experiments harvested samples at several time points. To reveal the dynamic gene expression changes over time, we need to identify the significant genes and detect the patterns of gene expressions, which may bring directional errors. Guo et al. (Biometrics 66(2):485-492, 2010) introduced a mixed directional false discovery rate (mdFDR) controlled procedure, which controls the sum of expected proportions of Type I and Type III errors among all rejections. In this paper, we develop weighted p value procedures for mdFDR control and give out some sufficient conditions to assure the (asymptotic) mdFDR control. Some weights and their estimators are illustrated to satisfy the sufficient conditions. The proposed weighted p value procedures are compared with the existing method by extensive simulations. Based on the proposed weighted p values procedure, we provide multiple CIs which control the false coverage-statement rate (FCR). We use the proposed methods to analyze the time-course microarray data studied in Lobenhofer et al. (Mol Endocrinol 16:1215-1229, 2002). Most of our findings are the same as those obtained by the existing method. In addition, we identify some other important genes, such as CDKN3 and NQO1.

Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations. Examples of methyl-donor mediated epigenetic effects include the changes in coat color and body weight in offspring when pregnant agouti mice are fed high choline, high methyl diets; the changes in tail kinking in offspring when pregnant Axin(Fu) mice are fed high choline, high methyl diets; the changes in Cdkn3 methylation and altered brain development that occurs in offspring when pregnant rodents are fed low choline diets. When choline metabolism is disrupted by deleting the gene Bhmt, DNA methylation is affected (especially in a region of chromosome 13), expression of specific genes is suppressed, and liver cancers develop. Better understanding of how nutrients such as choline and methyl-donors influence epigenetic programs has importance for our understanding of not only developmental abnormalities but also for understanding the origins of chronic diseases.