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Abstract Background High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers. Results We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation. Conclusions Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level.

Abstract Background DNA methylation patterns have been shown to significantly correlate with different tissue types and disease states. High-throughput methylation arrays enable large-scale DNA methylation analysis to identify informative DNA methylation biomarkers. The identification of disease-specific methylation signatures is of fundamental and practical interest for risk assessment, diagnosis, and prognosis of diseases. Results Using published high-throughput DNA methylation data, a two-stage feature selection method was developed to select a small optimal subset of DNA methylation features to precisely classify two sample groups. With this approach, a small number of CpG sites were highly sensitive and specific in distinguishing lung cancer tissue samples from normal lung tissue samples. Conclusion This study shows that it is feasible to identify DNA methylation biomarkers from high-throughput DNA methylation profiles and that a small number of signature CpG sites can suffice to classify two groups of samples. The computational method we developed in the study is efficient to identify signature CpG sites from disease samples with complex methylation patterns.

Abstract Background Changes in gene expression are known to be responsible for phenotypic variation and susceptibility to diseases. Identification and annotation of the genomic sequence variants that cause gene expression changes is therefore likely to lead to a better understanding of the cause of disease at the molecular level. In this study we investigate the pattern of single nucleotide polymorphisms (SNPs) in genes for which the mRNA levels show cis-genetic linkage (gene expression quantitative trait loci mapping in cis, or cis-eQTLs) in segregating mouse populations. Such genes are expected to have polymorphisms near their physical location (cis-variations) that affect their mRNA levels by altering one or more of the cis-regulatory elements. This led us to characterize the SNPs in promoter (5 Kb upstream) and non-coding gene regions (introns and 5 Kb downstream) (cis-SNPs) and the effects they may have on putative transcription factor binding sites. Results We demonstrate that the cis-eQTL genes (CEGs) have a significantly higher frequency of cis-SNPs compared to non-CEGs (when both sets are taken from the non-IBD regions, i.e. regions not identical by descent). Most CEGs having cis-SNPs do not contain these SNPs in the phylogenetically conserved regions. In those CEGs that contain cis-SNPs in the phylogenetically conserved regions, enrichment of cis-SNPs occurs both within and outside of the conserved sequences. A higher fraction of CEGs are also seen to harbor cis-SNP that affect predicted transcription factor binding sites, a likely consequence of the higher cis-SNPs density in these genes. Conclusion This present study provides the first genome-wide investigation of the putative cis-regulatory variations in a large set of genes whose levels of expression give rise to cis-linkage in segregating mammalian populations. Our results provide insights into the challenges that exist in identifying polymorphisms regulating gene expression using bioinformatic sequence analysis approaches. The data provided herein should benefit future investigations in this area.

Yeast mutants, delta-rtg1 and delta-rtg2, which contain dysfunctional alleles of RTG1 and RTG2 genes are unable to grow when acetate is the only carbon source and show glutamate and aspartate auxotrophy but anabolism and energy production and transport are unaffected. These mutants show a decrease in the activities of mitochondrial citrate synthase (CS1), acetyl-CoA synthase, NAD isocitrate dehydrogenase and pyruvate carboxylase. The ability to grow in acetate is restored by an overexpression of CS1 in the mutants but the glutamate and aspartate auxotrophy is unaffected.

Abstract Objective To investigate the incidence of and risk factors associated with negative postoperative behavioral changes (NPOBCs) in children undergoing painless gastroscopy. Methods Inclusion criteria: ASA I–II and outpatients aged 6–12 years undergoing painless gastroscopy. Exclusion criteria: history of surgery or anesthesia, children with developmental or intellectual abnormalities, refusal to participate, preoperative abdominal pain score > 3 points, history of chronic abdominal pain of > 3 months duration, and serious intraoperative complications. On the 1st, 14th, and 30th day after the gastroscopy, the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) was used to assess NPOBCs in children. Results A total of 1,670 children were included in this prospective observational cohort study. The incidence rates of NPOBCs were 14.13%, 4.55%, and 2.14% on the 1st, 14th, and 30th day after gastroscopy, respectively. The risk factors for the first day were female sex (OR 1.34, 95% CI 1.00–1.79), parental anxiety (OR 2.23, 95% CI 1.75–3.12), and severe anxiety in children (OR 2.83, 95% CI 1.96–4.07). The risk factors on the 14th day were parental anxiety (OR 3.71, 95% CI 2.19–6.29), a parental educational level above high school (OR 1.65, 95% CI 1.00–2.70), and severe anxiety in children (OR 11.87, 95% CI 5.85–24.07). The risk factors on the 30th day were female sex (OR 2.99, 95% CI 1.41–6.34), being an only child (OR 4.42, 95% CI 2.18–8.95), a parental educational level above high school (OR 2.66, 95% CI 1.27 NPOBCs 5.56), and severe anxiety in children (OR 6.84, 95% CI 2.84–16.49). Conclusion In children undergoing painless gastroscopy, the incidence rates of NPOBCs on the 1st, 14th, and 30th day were 14.13%, 4.55%, and 2.14%, respectively. The risk factors for NPOBCs were severe anxiety in children, female sex, parental anxiety, and a parental educational level above high school. In particular, severe preoperative anxiety in children was a persistent risk factor for NPOBCs within 30 days.