24 research outputs found
Generating High Density, Low Cost Genotype Data in Soybean [\u3ci\u3eGlycine max\u3c/i\u3e (L.) Merr.]
Obtaining genome-wide genotype information for millions of SNPs in soybean [Glycine max (L.) Merr.] often involves completely resequencing a line at 5X or greater coverage. Currently, hundreds of soybean lines have been resequenced at high depth levels with their data deposited in the NCBI Short Read Archive. This publicly available dataset may be leveraged as an imputation reference panel in combination with skim (low coverage) sequencing of new soybean genotypes to economically obtain high-density SNP information. Ninety-nine soybean lines resequenced at an average of 17.1X were used to generate a reference panel, with over 10 million SNPs called using GATK’s Haplotype Caller tool. Whole genome resequencing at approximately 1X depth was performed on 114 previously ungenotyped experimental soybean lines. Coverages down to 0.1X were analyzed by randomly subsetting raw reads from the original 1X sequence data. SNPs discovered in the reference panel were genotyped in the experimental lines after aligning to the soybean reference genome, and missing markers imputed using Beagle 4.1. Sequencing depth of the experimental lines could be reduced to 0.3X while still retaining an accuracy of 97.8%. Accuracy was inversely related to minor allele frequency, and highly correlated with marker linkage disequilibrium. The high accuracy of skim sequencing combined with imputation provides a low cost method for obtaining dense genotypic information that can be used for various genomics applications in soybean
ChemBank: a small-molecule screening and cheminformatics resource database
ChemBank (http://chembank.broad.harvard.edu/) is a public, web-based informatics environment developed through a collaboration between the Chemical Biology Program and Platform at the Broad Institute of Harvard and MIT. This knowledge environment includes freely available data derived from small molecules and small-molecule screens and resources for studying these data. ChemBank is unique among small-molecule databases in its dedication to the storage of raw screening data, its rigorous definition of screening experiments in terms of statistical hypothesis testing, and its metadata-based organization of screening experiments into projects involving collections of related assays. ChemBank stores an increasingly varied set of measurements derived from cells and other biological assay systems treated with small molecules. Analysis tools are available and are continuously being developed that allow the relationships between small molecules, cell measurements, and cell states to be studied. Currently, ChemBank stores information on hundreds of thousands of small molecules and hundreds of biomedically relevant assays that have been performed at the Broad Institute by collaborators from the worldwide research community. The goal of ChemBank is to provide life scientists unfettered access to biomedically relevant data and tools heretofore available primarily in the private sector
Age-based disparities in end-of-life decisions in Belgium: a population-based death certificate survey
<p>Abstract</p> <p>Background</p> <p>A growing body of scientific research is suggesting that end-of-life care and decision making may differ between age groups and that elderly patients may be the most vulnerable to exclusion of due care at the end of life. This study investigates age-related disparities in the rate of end-of-life decisions with a possible or certain life shortening effect (ELDs) and in the preceding decision making process in Flanders, Belgium in 2007, where euthanasia was legalised in 2002. Comparing with data from an identical survey in 1998 we also study the plausibility of the ‘slippery slope’ hypothesis which predicts a rise in the rate of administration of life ending drugs without patient request, especially among elderly patients, in countries where euthanasia is legal.</p> <p>Method</p> <p>We performed a post-mortem survey among physicians certifying a large representative sample (n = 6927) of death certificates in 2007, identical to a 1998 survey. Response rate was 58.4%.</p> <p>Results</p> <p>While the rates of non-treatment decisions (NTD) and administration of life ending drugs without explicit request (LAWER) did not differ between age groups, the use of intensified alleviation of pain and symptoms (APS) and euthanasia/assisted suicide (EAS), as well as the proportion of euthanasia requests granted, was bivariately and negatively associated with patient age. Multivariate analysis showed no significant effects of age on ELD rates. Older patients were less often included in decision making for APS and more often deemed lacking in capacity than were younger patients. Comparison with 1998 showed a decrease in the rate of LAWER in all age groups except in the 80+ age group where the rate was stagnant.</p> <p>Conclusion</p> <p>Age is not a determining factor in the rate of end-of-life decisions, but is in decision making as patient inclusion rates decrease with old age. Our results suggest there is a need to focus advance care planning initiatives on elderly patients. The slippery slope hypothesis cannot be confirmed either in general or among older people, as since the euthanasia law fewer LAWER cases were found.</p
The Evolutionary Genetics and Emergence of Avian Influenza Viruses in Wild Birds
We surveyed the genetic diversity among avian influenza virus (AIV) in wild birds, comprising 167 complete viral genomes from 14 bird species sampled in four locations across the United States. These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection. Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment. From this, we propose that AIV in wild birds forms transient “genome constellations,” continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses
Comparing a Mixed Model Approach to Traditional Stability Estimators for Mapping Genotype by Environment Interactions and Yield Stability in Soybean [Glycine max (L.) Merr.]
Identifying genetic loci associated with yield stability has helped plant breeders and geneticists begin to understand the role and influence of genotype by environment (GxE) interactions in soybean [Glycine max (L.) Merr.] productivity, as well as other crops. Quantifying a genotype’s range of performance across testing locations has been developed over decades with dozens of methodologies available. This includes directly modeling GxE interactions as part of an overall model for yield, as well as methods which generate overall yield “stability” values from multi-environment trial data. Correspondence between these methods as it pertains to the outcomes of genome wide association studies (GWAS) has not been well defined. In this study, the GWAS results for yield and yield stability were compared in 213 soybean lines across 11 environments to determine their utility and potential intersection. Both univariate and multivariate conventional stability estimates were considered alongside a mixed model for yield that fit marker by environment interactions as a random effect. One-hundred and six total QTL were discovered across all mapping results, however, genetic loci that were significant in the mixed model for grain yield that fit marker by environment interactions were completely distinct from those that were significant when mapping using traditional stability measures as a phenotype. Furthermore, 73.21% of QTL discovered in the mixed model were determined to cause a crossover interaction effect which cause genotype rank changes between environments. Overall, the QTL discovered via explicitly mapping GxE interactions also explained more yield variance that those QTL associated with differences in traditional stability estimates making their theoretical impact on selection greater. A lack of intersecting results between mapping approaches highlights the importance of examining stability in multiple contexts when attempting to manipulate GxE interactions in soybean
Generating High Density, Low Cost Genotype Data in Soybean [Glycine max (L.) Merr.]
Obtaining genome-wide genotype information for millions of SNPs in soybean [Glycine max (L.) Merr.] often involves completely resequencing a line at 5X or greater coverage. Currently, hundreds of soybean lines have been resequenced at high depth levels with their data deposited in the NCBI Short Read Archive. This publicly available dataset may be leveraged as an imputation reference panel in combination with skim (low coverage) sequencing of new soybean genotypes to economically obtain high-density SNP information. Ninety-nine soybean lines resequenced at an average of 17.1X were used to generate a reference panel, with over 10 million SNPs called using GATK’s Haplotype Caller tool. Whole genome resequencing at approximately 1X depth was performed on 114 previously ungenotyped experimental soybean lines. Coverages down to 0.1X were analyzed by randomly subsetting raw reads from the original 1X sequence data. SNPs discovered in the reference panel were genotyped in the experimental lines after aligning to the soybean reference genome, and missing markers imputed using Beagle 4.1. Sequencing depth of the experimental lines could be reduced to 0.3X while still retaining an accuracy of 97.8%. Accuracy was inversely related to minor allele frequency, and highly correlated with marker linkage disequilibrium. The high accuracy of skim sequencing combined with imputation provides a low cost method for obtaining dense genotypic information that can be used for various genomics applications in soybean