The technique 'joint and individual variance explained' highlights persistent aspects of the diet using longitudinal food frequency data.

Dietary pattern analysis is typically based on dimension reduction and summarises the diet with a small number of scores. We assess 'joint and individual variance explained' (JIVE) as a method for extracting dietary patterns from longitudinal data that highlights elements of the diet that are associated over time. The Auckland Birthweight Collaborative Study, in which participants completed an FFQ at ages 3·5 (n 549), 7 (n 591) and 11 (n 617), is used as an example. Data from each time point are projected onto the directions of shared variability produced by JIVE to yield dietary patterns and scores. We assess the ability of the scores to predict future BMI and blood pressure measurements of the participants and make a comparison with principal component analysis (PCA) performed separately at each time point. The diet could be summarised with three JIVE patterns. The patterns were interpretable, with the same interpretation across age groups: a vegetable and whole grain pattern, a sweets and meats pattern and a cereal v. sweet drinks pattern. The first two PCA-derived patterns were similar across age groups and similar to the first two JIVE patterns. The interpretation of the third PCA pattern changed across age groups. Scores produced by the two techniques were similarly effective in predicting future BMI and blood pressure. We conclude that when data from the same participants at multiple ages are available, JIVE provides an advantage over PCA by extracting patterns with a common interpretation across age groups.

The relationship between 25-hydroxyvitamin D concentration in early pregnancy and pregnancy outcomes in a large, prospective cohort.

Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations 75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.

Chromosome conformation maps in fission yeast reveal cell cycle dependent sub nuclear structure.

Successful progression through the cell cycle requires spatial and temporal regulation of gene transcript levels and the number, positions and condensation levels of chromosomes. Here we present a high resolution survey of genome interactions in Schizosaccharomyces pombe using synchronized cells to investigate cell cycle dependent changes in genome organization and transcription. Cell cycle dependent interactions were captured between and within S. pombe chromosomes. Known features of genome organization (e.g. the clustering of telomeres and retrotransposon long terminal repeats (LTRs)) were observed throughout the cell cycle. There were clear correlations between transcript levels and chromosomal interactions between genes, consistent with a role for interactions in transcriptional regulation at specific stages of the cell cycle. In silico reconstructions of the chromosome organization within the S. pombe nuclei were made by polymer modeling. These models suggest that groups of genes with high and low, or differentially regulated transcript levels have preferred positions within the S. pombe nucleus. We conclude that the S. pombe nucleus is spatially divided into functional sub-nuclear domains that correlate with gene activity. The observation that chromosomal interactions are maintained even when chromosomes are fully condensed in M phase implicates genome organization in epigenetic inheritance and bookmarking.

Genome conformation capture reveals that the Escherichia coli chromosome is organized by replication and transcription.

To fit within the confines of the cell, bacterial chromosomes are highly condensed into a structure called the nucleoid. Despite the high degree of compaction in the nucleoid, the genome remains accessible to essential biological processes, such as replication and transcription. Here, we present the first high-resolution chromosome conformation capture-based molecular analysis of the spatial organization of the Escherichia coli nucleoid during rapid growth in rich medium and following an induced amino acid starvation that promotes the stringent response. Our analyses identify the presence of origin and terminus domains in exponentially growing cells. Moreover, we observe an increased number of interactions within the origin domain and significant clustering of SeqA-binding sequences, suggesting a role for SeqA in clustering of newly replicated chromosomes. By contrast, 'histone-like' protein (i.e. Fis, IHF and H-NS) -binding sites did not cluster, and their role in global nucleoid organization does not manifest through the mediation of chromosomal contacts. Finally, genes that were downregulated after induction of the stringent response were spatially clustered, indicating that transcription in E. coli occurs at transcription foci.

Shortest path analysis using partial correlations for classifying gene functions from gene expression data.

MOTIVATION: Gaussian graphical models (GGMs) are a popular tool for representing gene association structures. We propose using estimated partial correlations from these models to attach lengths to the edges of the GGM, where the length of an edge is inversely related to the partial correlation between the gene pair. Graphical lasso is used to fit the GGMs and obtain partial correlations. The shortest paths between pairs of genes are found. Where terminal genes have the same biological function intermediate genes on the path are classified as having the same function. We validate the method using genes of known function using the Rosetta Compendium of yeast (Saccharomyces Cerevisiae) gene expression profiles. We also compare our results with those obtained using a graph constructed using correlations. RESULTS: Using a partial correlation graph, we are able to classify approximately twice as many genes to the same level of accuracy as when using a correlation graph. More importantly when both methods are tuned to classify a similar number of genes, the partial correlation approach can increase the accuracy of the classifications.

Oral vitamin D3 supplementation for chronic plaque psoriasis: a randomized, double-blind, placebo-controlled trial.

PURPOSE: The management of psoriasis remains a challenge for dermatologist and patient. This study aimed to determine whether vitamin D3 supplementation improves psoriasis compared to placebo. MATERIALS AND METHODS: In a randomized, doubled-blind, placebo-controlled trial, 101 participants ≥18 years with psoriasis were grouped by severity and allocated to 100,000 International Units (IU) vitamin D3/month for 12 months (200,000 IU at baseline; n = 67) or an identical placebo (n = 34). Psoriasis Area and Severity Index (PASI) and serum 25(OH)D concentrations were assessed at 3-monthly intervals. The primary outcome was the difference in PASI between groups over time. The relationship between 25(OH)D and PASI across the sample was also considered in a post hoc analysis. RESULTS: PASI did not differ between groups at any time (group F(1, 104) = 0.48, p = .49; group*time F(4, 384) = 0.26, p = .90). However, 25(OH)D increased in both groups, rendering these findings inconclusive. A significant inverse relationship existed between PASI and 25(OH)D, with elevation of 25(OH)D by up to 125 nmol/L associated with mild decreases in PASI (estimated range of decrease 0-2.6; p = .002). CONCLUSIONS: A direct benefit of vitamin D3 supplementation for psoriasis could not be determined. However, these findings suggest a relationship between 25(OH)D and psoriasis severity, at least in some subgroups. Australian New Zealand Clinical Trials Registry #12611000648921.

Mitochondrial-nuclear DNA interactions contribute to the regulation of nuclear transcript levels as part of the inter-organelle communication system.

Nuclear and mitochondrial organelles must maintain a communication system. Loci on the mitochondrial genome were recently reported to interact with nuclear loci. To determine whether this is part of a DNA based communication system we used genome conformation capture to map the global network of DNA-DNA interactions between the mitochondrial and nuclear genomes (Mito-nDNA) in Saccharomyces cerevisiae cells grown under three different metabolic conditions. The interactions that form between mitochondrial and nuclear loci are dependent on the metabolic state of the yeast. Moreover, the frequency of specific mitochondrial-nuclear interactions (i.e. COX1-MSY1 and Q0182-RSM7) showed significant reductions in the absence of mitochondrial encoded reverse transcriptase machinery. Furthermore, these reductions correlated with increases in the transcript levels of the nuclear loci (MSY1 and RSM7). We propose that these interactions represent an inter-organelle DNA mediated communication system and that reverse transcription of mitochondrial RNA plays a role in this process.

Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions.

In recent years there has been considerable and growing interest in the 3-dimensional organization of genomes. In this manuscript we present an integrated computational-molecular study that produces an ensemble of high-resolution 3-dimensional conformations of the budding yeast genome. The compaction, folding and spatial organization of the chromosomes was based on empirical data determined using proximity-based ligation. Our models incorporate external constraints that allow the separation of gross organizational effects from those due to local interactions. Our models show that yeast chromosomes have preferred yet non-exclusive positions. They also identify interaction dependent clustering of tRNAs, early firing origins of replication, and Gal4 protein binding sites, yet the cluster composition is dynamic. Our results support a link between structure and transcription that occurs within the context of a flexible genome organization.