An updated meta-analysis approach for genetic linkage

We present a meta-analysis procedure for genome-wide linkage studies (MAGS). The MAGS procedure combines genome-wide linkage results across studies with possibly distinct marker maps. We applied the MAGS procedure to the simulated data from the Genetic Analysis Workshop 14 in order to investigate power to detect linkage to disease genes and power to detect linkage to disease modifier genes while controlling for type I error. We analyzed all 100 replicates of the four simulated studies for chromosomes 1 (disease gene), 2 (modifier gene), 3 (disease gene), 4 (no disease gene), 5 (disease gene), and 10 (modifier gene) with knowledge of the simulated disease gene locations. We found that the procedure correctly identified the disease loci on chromosomes 1, 3, and 5 and did not erroneously identify a linkage signal on chromosome 4. The MAGS procedure provided little to no evidence of linkage to the disease modifier genes on chromosomes 2 and 10

Tuberculosis in cattle: the results of the four-area project

<p/> <p>The four-area project was undertaken to further assess the impact of badger removal on the control of tuberculosis in cattle herds in Ireland. It was conducted between 1997 and 2002 in matched removal and reference areas in four counties, namely Cork, Donegal, Kilkenny and Monaghan, representing a wide range of Irish farming environments. In the removal areas, a proactive programme of badger removal was conducted, on two or three occasions each year, whereas in the reference areas, badger removal was entirely reactive following severe outbreaks of tuberculosis amongst cattle. A detailed statistical analysis of this study has already been presented by Griffin <it>et al. </it><abbrgrp><abbr bid="B13">13</abbr></abbrgrp>; this paper presents further, mainly descriptive, findings from the study. In total, 2,360 badgers were captured in the removal areas of which 450 (19.5%) were considered positive for tuberculosis and 258 badgers were captured in the reference areas, with 57 (26.1%) positive for tuberculosis. The annual incidence of confirmed herd restrictions was lower in the removal area compared to the reference area in every year of the study period in each of the four counties. These empirical findings were consistent with the hazard ratios found by Griffin <it>et al. </it><abbrgrp><abbr bid="B13">13</abbr></abbrgrp>. Further, the effect of proactive badger removal on cattle tuberculosis in the four-area project and in the earlier east-Offaly project, as measured using the number of reactors per 1,000 cattle tested, were very similar, providing compelling evidence of the role of badgers in the epidemiology of tuberculosis in Irish cattle herds. The validity of the four-area project was discussed in detail. Efforts to minimise badger-to-cattle transmission in Ireland must be undertaken in association with the current comprehensive control programme, which has effectively minimised opportunities for cattle-to-cattle transmission.</p

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Photoabsorption and photoion spectroscopy of atomic uranium in the region of 6p and 5d excitations

The photoabsorption process in atomic uranium has been investigated experimentally and theoretically in the 15–150-eV region. Using the dual laser plasma technique, the 6p photoabsorption spectrum has been recorded while for the first time the 5d region has been remeasured photoelectrically using both photoabsorption and photoion spectroscopy. Interpretation of the photoabsorption spectra is supported by Hartree-Fock calculations which take into account spin-flip decay and the interaction of many discrete states with many continua. The 6p spectrum is entirely dominated by spin-orbit split 6p⃗6d transitions. The 5d-subshell photoabsorption is shown to consist predominantly of discrete 5d⃗5f excitations; here the electrostatic and spin-orbit interactions are comparable in strength

Avaliação da Vergonha em Adolescentes: ‘The Other as Shamer Scale’

Shame, as a self-conscious, multidimensional and socially focused emotion, plays a central role in the mental health of individuals. In adolescents, shame is also a frequent experience and its assessment is important for research and clinical practice. This study aims to validate a brief measure of external shame (Other as Shamer Scale – brief version for adolescents: (OASB-A). The participants were 834 adolescents with a mean age of 15 years. The final model of the OASB-A (8 items), obtained through CFA, presents a good fit to the data. The OASB-A shows a good internal consistency and an adequate temporal reliability. The OASB-A also reveals significant correlations with traumatic shame experiences (IES-R) and psychopathological symptoms (DASS-21). The OASB-A is an economic and reliable measure to assess external shame in adolescents

ART: A machine learning Automated Recommendation Tool for synthetic biology

Biology has changed radically in the last two decades, transitioning from a descriptive science into a design science. Synthetic biology allows us to bioengineer cells to synthesize novel valuable molecules such as renewable biofuels or anticancer drugs. However, traditional synthetic biology approaches involve ad-hoc engineering practices, which lead to long development times. Here, we present the Automated Recommendation Tool (ART), a tool that leverages machine learning and probabilistic modeling techniques to guide synthetic biology in a systematic fashion, without the need for a full mechanistic understanding of the biological system. Using sampling-based optimization, ART provides a set of recommended strains to be built in the next engineering cycle, alongside probabilistic predictions of their production levels. We demonstrate the capabilities of ART on simulated data sets, as well as experimental data from real metabolic engineering projects producing renewable biofuels, hoppy flavored beer without hops, and fatty acids. Finally, we discuss the limitations of this approach, and the practical consequences of the underlying assumptions failing

Taxonomy based on science is necessary for global conservation

Peer reviewe

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications

Sequencing-based DNA methylation profiling methods are comprehensive and, as accuracy and affordability improve, will increasingly supplant microarrays for genome-scale analyses. Here, four sequencing-based methodologies were applied to biological replicates of human embryonic stem cells to compare their CpG coverage genome-wide and in transposons, resolution, cost, concordance and its relationship with CpG density and genomic context. The two bisulfite methods reached concordance of 82% for CpG methylation levels and 99% for non-CpG cytosine methylation levels. Using binary methylation calls, two enrichment methods were 99% concordant, while regions assessed by all four methods were 97% concordant. To achieve comprehensive methylome coverage while reducing cost, an approach integrating two complementary methods was examined. The integrative methylome profile along with histone methylation, RNA, and SNP profiles derived from the sequence reads allowed genome-wide assessment of allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression