Chickspress: a resource for chicken gene expression

High-throughput sequencing and proteomics technologies are markedly increasing the amount of RNA and peptide data that are available to researchers, which are typically made publicly available via data repositories such as the NCBI Sequence Read Archive and proteome archives, respectively. These data sets contain valuable information about when and where gene products are expressed, but this information is not readily obtainable from archived data sets. Here we report Chickspress (http://geneatlas.arl.arizona.edu), the first publicly available gene expression resource for chicken tissues. Since there is no single source of chicken gene models, Chickspress incorporates both NCBI and Ensembl gene models and links these gene sets with experimental gene expression data and QTL information. By linking gene models from both NCBI and Ensembl gene prediction pipelines, researchers can, for the first time, easily compare gene models from each of these prediction workflows to available experimental data for these products. We use Chickspress data to show the differences between these gene annotation pipelines. Chickspress also provides rapid search, visualization and download capacity for chicken gene sets based upon tissue type, developmental stage and experiment type. This first Chickspress release contains 161 gene expression data sets, including expression of mRNAs, miRNAs, proteins and peptides. We provide several examples demonstrating how researchers may use this resource.National Institutes of Health [R24 GM079326]; US Department of Agriculture National Institute of Food and Agriculture [2011-67015-30332]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Public Platform for the Verification of the Phenotypic Effect of Candidate Genes for Resistance to Aflatoxin Accumulation and Aspergillus flavus Infection in Maize

A public candidate gene testing pipeline for resistance to aflatoxin accumulation or Aspergillus flavus infection in maize is presented here. The pipeline consists of steps for identifying, testing, and verifying the association of selected maize gene sequences with resistance under field conditions. Resources include a database of genetic and protein sequences associated with the reduction in aflatoxin contamination from previous studies; eight diverse inbred maize lines for polymorphism identification within any maize gene sequence; four Quantitative Trait Loci (QTL) mapping populations and one association mapping panel, all phenotyped for aflatoxin accumulation resistance and associated phenotypes; and capacity for Insertion/Deletion (InDel) and SNP genotyping in the population(s) for mapping. To date, ten genes have been identified as possible candidate genes and put through the candidate gene testing pipeline, and results are presented here to demonstrate the utility of the pipeline

Facilitating functional annotation of chicken microarray data

<p>Abstract</p> <p>Background</p> <p>Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO). However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information.</p> <p>Results</p> <p>We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (<it>AGOM</it>) tool to help researchers to quickly retrieve corresponding functional information for their dataset.</p> <p>Conclusion</p> <p>Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using <it>AGOM </it>tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and will be updated on regular basis.</p

AgBase: supporting functional modeling in agricultural organisms

AgBase (http://www.agbase.msstate.edu/) provides resources to facilitate modeling of functional genomics data and structural and functional annotation of agriculturally important animal, plant, microbe and parasite genomes. The website is redesigned to improve accessibility and ease of use, including improved search capabilities. Expanded capabilities include new dedicated pages for horse, cat, dog, cotton, rice and soybean. We currently provide 590 240 Gene Ontology (GO) annotations to 105 454 gene products in 64 different species, including GO annotations linked to transcripts represented on agricultural microarrays. For many of these arrays, this provides the only functional annotation available. GO annotations are available for download and we provide comprehensive, species-specific GO annotation files for 18 different organisms. The tools available at AgBase have been expanded and several existing tools improved based upon user feedback. One of seven new tools available at AgBase, GOModeler, supports hypothesis testing from functional genomics data. We host several associated databases and provide genome browsers for three agricultural pathogens. Moreover, we provide comprehensive training resources (including worked examples and tutorials) via links to Educational Resources at the AgBase website

Social anxiety in pre-adolescent children: what do we know about maintenance?

The cognitive theory of social anxiety disorder (SAD) is one of the most widely accepted accounts of the maintenance of the disorder in adults, yet it remains unknown if, or to what extent, the same cognitive and behavioral maintenance mechanisms that occur in adult SAD also apply to SAD among pre-adolescent children. In contrast to the adult literature, current models of SAD in children mostly account for etiology and maintenance processes are given limited attention. Consequently, their clinical utility for the treatment of SAD in children may be limited. This narrative review, first, critically examines the different theoretical conceptualizations of the maintenance of social anxiety in the child and adult literature and illustrates how these have resulted in different treatment approaches and clinical understanding. Second, it reviews the available evidence relating to hypotheses about the maintenance of SAD in children as derived from adult cognitive and etiological models. Third, it highlights the need to attend directly to child specific maintenance mechanisms in SAD, to draw on cognitive theory, and to account for the influence of childhood-specific contextual (e.g. family and school-based interactions) and developmental factors on children's social experiences

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570