Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Low frequency radio properties of the z>5 quasar population

Optically luminous quasars at z > 5 are important probes of super-massive black hole (SMBH) formation. With new and future radio facilities, the discovery of the brightest low-frequency radio sources in this epoch would be an important new probe of cosmic reionization through 21-cm absorption experiments. In this work, we systematically study the low-frequency radio properties of a sample of 115 known spectroscopically confirmed z > 5 quasars using the second data release of the Low Frequency Array (LOFAR) Two Metre Sky survey (LoTSS-DR2), reaching noise levels of ∼80 µJy beam−1 (at 144 MHz) over an area of ∼ 5720 deg2 . We find that 41 sources (36%) are detected in LoTSS-DR2 at > 2σ significance and we explore the evolution of their radio properties (power, spectral index, and radio loudness) as a function of redshift and rest-frame ultra-violet properties. We obtain a median spectral index of −0.29+0.10 −0.09 by stacking 93 quasars using LoTSS-DR2 and Faint Images of the Radio Sky at Twenty Centimetres (FIRST) data at 1.4 GHz, in line with observations of quasars at z < 3. We compare the radio loudness of the high-z quasar sample to a lower-z quasar sample at z ∼ 2 and find that the two radio loudness distributions are consistent with no evolution, although the low number of high-z quasars means that we cannot rule out weak evolution. Furthermore, we make a first order empirical estimate of the z = 6 quasar radio luminosity function, which is used to derive the expected number of high-z sources that will be detected in the completed LoTSS survey. This work highlights the fact that new deep radio observations can be a valuable tool in selecting high-z quasar candidates for follow-up spectroscopic observations by decreasing contamination of stellar dwarfs and reducing possible selection biases introduced by strict colour cuts

Genetic Patterns of Domestication in Pigeonpea (Cajanus cajan (L.) Millsp.) and Wild Cajanus Relatives

Pigeonpea (Cajanus cajan) is an annual or short-lived perennial food legume of acute regional importance, providing significant protein to the human diet in less developed regions of Asia and Africa. Due to its narrow genetic base, pigeonpea improvement is increasingly reliant on introgression of valuable traits from wild forms, a practice that would benefit from knowledge of its domestication history and relationships to wild species. Here we use 752 single nucleotide polymorphisms (SNPs) derived from 670 low copy orthologous genes to clarify the evolutionary history of pigeonpea (79 accessions) and its wild relatives (31 accessions). We identified three well-supported lineages that are geographically clustered and congruent with previous nuclear and plastid sequence-based phylogenies. Among all species analyzed Cajanus cajanifolius is the most probable progenitor of cultivated pigeonpea. Multiple lines of evidence suggest recent gene flow between cultivated and non-cultivated forms, as well as historical gene flow between diverged but sympatric species. Evidence supports that primary domestication occurred in India, with a second and more recent nested population bottleneck focused in tropical regions that is the likely consequence of pigeonpea breeding. We find abundant allelic variation and genetic diversity among the wild relatives, with the exception of wild species from Australia for which we report a third bottleneck unrelated to domestication within India. Domesticated C. cajan possess 75% less allelic diversity than the progenitor clade of wild Indian species, indicating a severe “domestication bottleneck” during pigeonpea domestication

Uncovering mechanisms of transcriptional regulations by systematic mining of cis regulatory elements with gene expression profiles

<p>Abstract</p> <p>Background</p> <p>Contrary to the traditional biology approach, where the expression patterns of a handful of genes are studied at a time, microarray experiments enable biologists to study the expression patterns of many genes simultaneously from gene expression profile data and decipher the underlying hidden biological mechanism from the observed gene expression changes. While the statistical significance of the gene expression data can be deduced by various methods, the biological interpretation of the data presents a challenge.</p> <p>Results</p> <p>A method, called CisTransMine, is proposed to help infer the underlying biological mechanisms for the observed gene expression changes in microarray experiments. Specifically, this method will predict potential cis-regulatory elements in promoter regions which could regulate gene expression changes. This approach builds on the MotifADE method published in 2004 and extends it with two modifications: up-regulated genes and down-regulated genes are tested separately and in addition, tests have been implemented to identify combinations of transcription factors that work synergistically. The method has been applied to a genome wide expression dataset intended to study myogenesis in a mouse C2C12 cell differentiation model. The results shown here both confirm the prior biological knowledge and facilitate the discovery of new biological insights.</p> <p>Conclusion</p> <p>The results validate that the CisTransMine approach is a robust method to uncover the hidden transcriptional regulatory mechanisms that can facilitate the discovery of mechanisms of transcriptional regulation.</p

An Open Access Database of Genome-wide Association Results

<p>Abstract</p> <p>Background</p> <p>The number of genome-wide association studies (GWAS) is growing rapidly leading to the discovery and replication of many new disease loci. Combining results from multiple GWAS datasets may potentially strengthen previous conclusions and suggest new disease loci, pathways or pleiotropic genes. However, no database or centralized resource currently exists that contains anywhere near the full scope of GWAS results.</p> <p>Methods</p> <p>We collected available results from 118 GWAS articles into a database of 56,411 significant SNP-phenotype associations and accompanying information, making this database freely available here. In doing so, we met and describe here a number of challenges to creating an open access database of GWAS results. Through preliminary analyses and characterization of available GWAS, we demonstrate the potential to gain new insights by querying a database across GWAS.</p> <p>Results</p> <p>Using a genomic bin-based density analysis to search for highly associated regions of the genome, positive control loci (e.g., MHC loci) were detected with high sensitivity. Likewise, an analysis of highly repeated SNPs across GWAS identified replicated loci (e.g., <it>APOE</it>, <it>LPL</it>). At the same time we identified novel, highly suggestive loci for a variety of traits that did not meet genome-wide significant thresholds in prior analyses, in some cases with strong support from the primary medical genetics literature (<it>SLC16A7, CSMD1, OAS1</it>), suggesting these genes merit further study. Additional adjustment for linkage disequilibrium within most regions with a high density of GWAS associations did not materially alter our findings. Having a centralized database with standardized gene annotation also allowed us to examine the representation of functional gene categories (gene ontologies) containing one or more associations among top GWAS results. Genes relating to cell adhesion functions were highly over-represented among significant associations (p < 4.6 × 10^-14), a finding which was not perturbed by a sensitivity analysis.</p> <p>Conclusion</p> <p>We provide access to a full gene-annotated GWAS database which could be used for further querying, analyses or integration with other genomic information. We make a number of general observations. Of reported associated SNPs, 40% lie within the boundaries of a RefSeq gene and 68% are within 60 kb of one, indicating a bias toward gene-centricity in the findings. We found considerable heterogeneity in information available from GWAS suggesting the wider community could benefit from standardization and centralization of results reporting.</p

Discovery of a radio galaxy at z = 5.72

We report the discovery of the most distant radio galaxy to date, TGSS1530 at a redshift of $z=5.72$ close to the presumed end of the Epoch of Reionisation. The radio galaxy was selected from the TGSS ADR1 survey at 150 MHz for having to an ultra-steep spectral index, $\alpha^{\textrm{150 MHz}}_{\textrm{1.4 GHz}} = -1.4$ and a compact morphology obtained using VLA imaging at 1.4 GHz. No optical or infrared counterparts for it were found in publicly available sky surveys. Follow-up optical spectroscopy at the radio position using GMOS on Gemini North revealed the presence of a single emission line. We identify this line as Lyman alpha at $z=5.72$, because of its asymmetric line profile, the absence of other optical/UV lines in the spectrum and a high equivalent width. With a Ly$\alpha$ luminosity of $5.7 \times 10^{42}$ erg s$^{-1}$ and a FWHM of $370$ km s$^{-1}$, TGSS1530 is comparable to `non-radio' Lyman alpha emitters (LAEs) at a similar redshift. However, with a radio luminosity of $\log L_{\textrm{150 MHz}} = 29.1$ W Hz$^{-1}$ and a deconvolved physical size $3.5$ kpc, its radio properties are similar to other known radio galaxies at $z>4$. Subsequent $J$ and $K$ band imaging using LUCI on the Large Binocular Telescope resulted in non-detection of the host galaxy down to $3\sigma$ limits of $J>24.4$ and $K>22.4$ (Vega). The $K$ band limit is consistent with $z>5$ from the $K-z$ relation for radio galaxies, suggesting stellar mass limits using simple stellar population models of $M_{\textrm{stars}}< 10^{10.5}$ $M_\odot$. Its high redshift coupled with relatively small radio and Ly$\alpha$ sizes suggest that TGSS1530 may be a radio galaxy in an early phase of its evolution.Comment: 11 pages, 7 figures. Latest published version 10 October 201

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Improving gene-set enrichment analysis of RNA-Seq data with small replicates

Deregulated pathways identified from transcriptome data of two sample groups have played a key role in many genomic studies. Gene-set enrichment analysis (GSEA) has been commonly used for pathway or functional analysis of microarray data, and it is also being applied to RNA-seq data. However, most RNA-seq data so far have only small replicates. This enforces to apply the gene-permuting GSEA method (or preranked GSEA) which results in a great number of false positives due to the inter-gene correlation in each gene-set. We demonstrate that incorporating the absolute gene statistic in one-tailed GSEA considerably improves the false-positive control and the overall discriminatory ability of the gene-permuting GSEA methods for RNA-seq data. To test the performance, a simulation method to generate correlated read counts within a gene-set was newly developed, and a dozen of currently available RNA-seq enrichment analysis methods were compared, where the proposed methods outperformed others that do not account for the inter-gene correlation. Analysis of real RNA-seq data also supported the proposed methods in terms of false positive control, ranks of true positives and biological relevance. An efficient R package (AbsFilterG- SEA) coded with C++ (Rcpp) is available from CRAN.open