ALBERT

Beschreibung: We give an arithmetic proof of rigidity for postcritically finite polynomials of prime power degree.

Beschreibung: We present a first determination of distances and extinctions for individual stars in the first release of the APOKASC catalogue, built from the joint efforts of the Apache Point Observatory Galactic Evolution Experiment ( APOGEE ) and the Kepler Asteroseismic Science Consortium (KASC). Our method takes into account the spectroscopic constraints derived from the APOGEE Stellar Parameters and Chemical Abundances Pipeline, together with the asteroseismic parameters from KASC. These parameters are then employed to estimate intrinsic stellar properties, including absolute magnitudes, using the Bayesian tool param . We then find the distance and extinction that best fit the observed photometry in Sloan Digital Sky Survey (SDSS), 2MASS, and WISE passbands. The first 1989 giants targetted by APOKASC are found at typical distances between 0.5 and 5 kpc, with individual uncertainties of just ~1.8 per cent. Our extinction estimates are systematically smaller than provided in the Kepler Input Catalogue and by the Schlegel et al. maps. Distances to individual stars in the NGC 6791 and NGC 6819 star clusters agree to within their credible intervals. Comparison with the APOGEE red clump and SAGA catalogues provide another useful check, exhibiting agreement with our measurements to within a few per cent. Overall, present methods seem to provide excellent distance and extinction determinations for the bulk of the APOKASC sample. Approximately one third of the stars present broad or multiple-peaked probability density functions and hence increased uncertainties. Uncertainties are expected to be reduced in future releases of the catalogue, when a larger fraction of the stars will have seismically determined evolutionary status classifications.

Beschreibung: Structural variation, including variation in gene copy number and presence or absence of genes, is a widespread and important source of genomic variation. We used whole-genome DNA sequences from 48 strains of Sinorhizobium (recently renamed Ensifer ), including 20 strains of Sinorhizobium meliloti and 12 strains of S. medicae that were the focus of the analyses, to study the fitness effects of new structural variants created by duplication and horizontal gene transfer. We find that derived duplicated and horizontally transferred (HT) genes segregate at lower frequency than synonymous and nonsynonymous nucleotide variants in S. meliloti and S. medicae . Furthermore, the relative frequencies of different types of variants are more similar in S. medicae than in S. meliloti , the species with the larger effective population size . These results are consistent with the hypothesis that most duplications and HT genes have deleterious effects. Diversity of duplications, as measured by segregating duplicated genes per gene, is greater than nucleotide diversity, consistent with a high rate of duplication. Our results suggest that the vast majority of structural variants found among closely related bacterial strains are short-lived and unlikely to be involved in species-wide adaptation.

Beschreibung: In a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experiment, an important consideration in experimental design is the minimum number of sequenced reads required to obtain statistically significant results. We present an extensive evaluation of the impact of sequencing depth on identification of enriched regions for key histone modifications (H3K4me3, H3K36me3, H3K27me3 and H3K9me2/me3) using deep-sequenced datasets in human and fly. We propose to define sufficient sequencing depth as the number of reads at which detected enrichment regions increase 〈1% for an additional million reads. Although the required depth depends on the nature of the mark and the state of the cell in each experiment, we observe that sufficient depth is often reached at 〈20 million reads for fly. For human, there are no clear saturation points for the examined datasets, but our analysis suggests 40–50 million reads as a practical minimum for most marks. We also devise a mathematical model to estimate the sufficient depth and total genomic coverage of a mark. Lastly, we find that the five algorithms tested do not agree well for broad enrichment profiles, especially at lower depths. Our findings suggest that sufficient sequencing depth and an appropriate peak-calling algorithm are essential for ensuring robustness of conclusions derived from ChIP-seq data.

Beschreibung: Background: Tissue dielectric properties are specific to physiological changes and consequently have been pursued as imaging biomarkers of cancer and other pathological disorders. However, a recent study (Phys Med Biol 52:2637-2656, 2007; Phys Med Biol 52:6093-6115, 2007), which utilized open-ended dielectric probing techniques and a previously established sensing volume, reported that the dielectric property contrast may only be 10% or less between breast cancer and normal fibroglandular tissue whereas earlier data suggested ratios of 4:1 and higher may exist. Questions about the sensing volume of this probe relative to the amount of tissue interrogated raise the distinct possibility that the conclusions drawn from that study may have been over interpreted. Methods: We performed open-ended dielectric probe measurements in two-layer compositions consisting of a background liquid and a planar piece of Teflon that was translated to predetermined distances away from the probe tip to assess the degree to which the probe produced property estimates representative of the compositional averages of the dielectric properties of the two materials resident within a small sensing volume around the tip of the probe. Results: When Teflon was in contact with the probe, the measured properties were essentially those of pure Teflon whereas the properties were nearly identical to those of the intervening liquid when the Teflon was located more than 2 mm from the probe tip. However, when the Teflon was moved closer to the probe tip, the dielectric property measurements were not linearly related to the compositional fraction of the two materials, but reflected nearly 50% of those of the intervening liquid at separation distances as small as 0.2 mm, and approximately 90% of the liquid when the Teflon was located 0.5 mm from the probe tip. Conclusion: These results suggest that the measurement methods reported in the most recent breast tissue dielectric property study are not likely to return the compositional averages of the breast tissue specimens evaluated, and thus, the conclusions reached about the expected dielectric property contrast in breast cancer from this specimen study may not be correct.

Beschreibung: Alterations in DNA methylation have been reported to occur during development and aging; however, much remains to be learned regarding post-natal and age-associated epigenome dynamics, and few if any investigations have compared human methylome patterns on a whole genome basis in cells from newborns and adults. The aim of this study was to reveal genomic regions with distinct structure and sequence characteristics that render them subject to dynamic post-natal developmental remodeling or age-related dysregulation of epigenome structure. DNA samples derived from peripheral blood monocytes and in vitro differentiated dendritic cells were analyzed by methylated DNA Immunoprecipitation (MeDIP) or, for selected loci, bisulfite modification, followed by next generation sequencing. Regions of interest that emerged from the analysis included tandem or interspersed-tandem gene sequence repeats (PCDHG , FAM90A , HRNR, ECEL1P2 ), and genes with strong homology to other family members elsewhere in the genome ( FZD1, FZD7 and FGF17 ). Our results raise the possibility that selected gene sequences with highly homologous copies may serve to facilitate, perhaps even provide a clock-like function for, developmental and age-related epigenome remodeling. If so, this would represent a fundamental feature of genome architecture in higher eukaryotic organisms.

Beschreibung: Motivation : Exome sequencing has proven to be an effective tool to discover the genetic basis of Mendelian disorders. It is well established that copy number variants (CNVs) contribute to the etiology of these disorders. However, calling CNVs from exome sequence data is challenging. A typical read depth strategy consists of using another sample (or a combination of samples) as a reference to control for the variability at the capture and sequencing steps. However, technical variability between samples complicates the analysis and can create spurious CNV calls. Results : Here , we introduce ExomeDepth, a new CNV calling algorithm designed to control for this technical variability. ExomeDepth uses a robust model for the read count data and uses this model to build an optimized reference set in order to maximize the power to detect CNVs. As a result, ExomeDepth is effective across a wider range of exome datasets than the previously existing tools, even for small (e.g. one to two exons) and heterozygous deletions. We used this new approach to analyse exome data from 24 patients with primary immunodeficiencies. Depending on data quality and the exact target region, we find between 170 and 250 exonic CNV calls per sample. Our analysis identified two novel causative deletions in the genes GATA2 and DOCK8 . Availability: The code used in this analysis has been implemented into an R package called ExomeDepth and is available at the Comprehensive R Archive Network (CRAN). Contact : v.plagnol@ucl.ac.uk Supplementary Information: Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation : New bioimaging techniques have recently been proposed to visualize the colocation or interaction of several proteins within individual cells, displaying the heterogeneity of neighbouring cells within the same tissue specimen. Such techniques could hold the key to understanding complex biological systems such as the protein interactions involved in cancer. However, there is a need for new algorithmic approaches that analyze the large amounts of multi-tag bioimage data from cancerous and normal tissue specimens to begin to infer protein networks and unravel the cellular heterogeneity at a molecular level. Results : The proposed approach analyzes cell phenotypes in normal and cancerous colon tissue imaged using the robotically controlled Toponome Imaging System microscope. It involves segmenting the 4',6-diamidino-2-phenylindole-labelled image into cells and determining the cell phenotypes according to their protein–protein dependence profile. These were analyzed using two new measures, Difference in Sums of Weighted cO-dependence/Anti-co-dependence profiles (DiSWOP and DiSWAP) for overall co-expression and anti-co-expression, respectively. These novel quantities were extracted using 11 Toponome Imaging System image stacks from either cancerous or normal human colorectal specimens. This approach enables one to easily identify protein pairs that have significantly higher/lower co-expression levels in cancerous tissue samples when compared with normal colon tissue. Availability and implementation: http://www2.warwick.ac.uk/fac/sci/dcs/research/combi/research/bic/diswop . Contact: v.n.kovacheva@warwick.ac.uk or Nasir.Rajpoot@ieee.org Supplementary Information: Supplementary data are available at Bioinformatics online.