Model SNP development for complex genomes based on hexaploid oat using high-throughput 454 sequencing technology

<p>Abstract</p> <p>Background</p> <p>Genetic markers are pivotal to modern genomics research; however, discovery and genotyping of molecular markers in oat has been hindered by the size and complexity of the genome, and by a scarcity of sequence data. The purpose of this study was to generate oat expressed sequence tag (EST) information, develop a bioinformatics pipeline for SNP discovery, and establish a method for rapid, cost-effective, and straightforward genotyping of SNP markers in complex polyploid genomes such as oat.</p> <p>Results</p> <p>Based on cDNA libraries of four cultivated oat genotypes, approximately 127,000 contigs were assembled from approximately one million Roche 454 sequence reads. Contigs were filtered through a novel bioinformatics pipeline to eliminate ambiguous polymorphism caused by subgenome homology, and 96 <it>in silico </it>SNPs were selected from 9,448 candidate loci for validation using high-resolution melting (HRM) analysis. Of these, 52 (54%) were polymorphic between parents of the Ogle1040 × TAM O-301 (OT) mapping population, with 48 segregating as single Mendelian loci, and 44 being placed on the existing OT linkage map. Ogle and TAM amplicons from 12 primers were sequenced for SNP validation, revealing complex polymorphism in seven amplicons but general sequence conservation within SNP loci. Whole-amplicon interrogation with HRM revealed insertions, deletions, and heterozygotes in secondary oat germplasm pools, generating multiple alleles at some primer targets. To validate marker utility, 36 SNP assays were used to evaluate the genetic diversity of 34 diverse oat genotypes. Dendrogram clusters corresponded generally to known genome composition and genetic ancestry.</p> <p>Conclusions</p> <p>The high-throughput SNP discovery pipeline presented here is a rapid and effective method for identification of polymorphic SNP alleles in the oat genome. The current-generation HRM system is a simple and highly-informative platform for SNP genotyping. These techniques provide a model for SNP discovery and genotyping in other species with complex and poorly-characterized genomes.</p

A chromosome‐scale reference of Chenopodium watsonii helps elucidate relationships within the North American A‐genome Chenopodium species and with quinoa

Abstract Quinoa (Chenopodium quinoa), an Andean pseudocereal, attained global popularity beginning in the early 2000s due to its protein quality, glycemic index, and high fiber, vitamin, and mineral contents. Pitseed goosefoot (Chenopodium berlandieri), quinoa's North American free‐living sister species, grows on disturbed and sandy substrates across the North America, including saline coastal sands, southwestern deserts, subtropical highlands, the Great Plains, and boreal forests. Together with South American avian goosefoot (Chenopodium hircinum) they comprise the American tetraploid goosefoot complex (ATGC). Superimposed on pitseed goosefoot's North American range are approximately 35 AA diploids, most of which are adapted to a diversity of niche environments. We chose to assemble a reference genome for Sonoran A‐genome Chenopodium watsonii due to fruit morphological and high (>99.3%) preliminary sequence‐match similarities with quinoa, along with its well‐established taxonomic status. The genome was assembled into 1377 scaffolds spanning 547.76 Mb (N50 = 55.14 Mb, L50 = 5), with 94% comprised in nine chromosome‐scale scaffolds and 93.9% Benchmarking Universal Single‐Copy Orthologs genes identified as single copy and 3.4% as duplicated. A high degree of synteny, with minor and mostly telomeric rearrangements, was found when comparing this taxon with the previously reported genome of South American C. pallidicaule and the A‐subgenome chromosomes of C. quinoa. Phylogenetic analysis was performed using 10,588 single‐nucleotide polymorphisms generated by resequencing a panel of 41 New World AA diploid accessions and the Eurasian H‐genome diploid Chenopodium vulvaria, along with three AABB tetraploids previously sequenced. Phylogenetic analysis of these 32 taxa positioned the psammophyte Chenopodium subglabrum on the branch containing A‐genome sequences from the ATGC. We also present evidence for long‐range dispersal of Chenopodium diploids between North and South America

Scientific Synergy between LSST and Euclid

Euclid and the Large Synoptic Survey Telescope (LSST) are poised to dramatically change the astronomy landscape early in the next decade. The combination of high-cadence, deep, wide-field optical photometry from LSST with high-resolution, wide-field optical photometry, and near-infrared photometry and spectroscopy from Euclid will be powerful for addressing a wide range of astrophysical questions. We explore Euclid/LSST synergy, ignoring the political issues associated with data access to focus on the scientific, technical, and financial benefits of coordination. We focus primarily on dark energy cosmology, but also discuss galaxy evolution, transient objects, solar system science, and galaxy cluster studies. We concentrate on synergies that require coordination in cadence or survey overlap, or would benefit from pixel-level co-processing that is beyond the scope of what is currently planned, rather than scientific programs that could be accomplished only at the catalog level without coordination in data processing or survey strategies. We provide two quantitative examples of scientific synergies: the decrease in photo-z errors (benefiting many science cases) when high-resolution Euclid data are used for LSST photo-z determination, and the resulting increase in weak-lensing signal-to-noise ratio from smaller photo-z errors. We briefly discuss other areas of coordination, including high-performance computing resources and calibration data. Finally, we address concerns about the loss of independence and potential cross-checks between the two missions and the potential consequences of not collaborating

Personalizing survival predictions in advanced colorectal cancer : The ARCAD nomogram project

Background: Estimating prognosis on the basis of clinicopathologic factors can inform clinical practice and improve risk stratification for clinical trials. We constructed prognostic nomograms for one-year overall survival and six-month progression-free survival in metastatic colorectal carcinoma by using the ARCAD database. Methods: Data from 22 674 patients in 26 randomized phase III clinical trials since 1997 were used to construct and validate Cox models, stratified by treatment arm within each study. Candidate variables included baseline age, sex, body mass index, performance status, colon vs rectal cancer, prior chemotherapy, number and location of metastatic sites, tumor mutation status (BRAF, KRAS), bilirubin, albumin, white blood cell count, hemoglobin, platelets, absolute neutrophil count, and derived neutrophil-to-lymphocyte ratio. Missing data (50% vs 50% vs < 50% probability] and actual [yes/no] overall and progression-free survival). Median survival predictions fell within the actual 95% Kaplan-Meier confidence intervals. Conclusions: The nomograms are well calibrated and internally and externally valid. They have the potential to aid prognostication and patient-physician communication and balance risk in colorectal cancer trials

Scientific Synergy Between LSST and Euclid

Euclid and the Large Synoptic Survey Telescope (LSST) are poised to dramatically change the astronomy landscape early in the next decade. The combination of high cadence, deep, wide-field optical photometry from LSST with high resolution, wide-field optical photometry and near-infrared photometry and spectroscopy from Euclid will be powerful for addressing a wide range of astrophysical questions. We explore Euclid/LSST synergy, ignoring the political issues associated with data access to focus on the scientific, technical, and financial benefits of coordination. We focus primarily on dark energy cosmology, but also discuss galaxy evolution, transient objects, solar system science, and galaxy cluster studies. We concentrate on synergies that require coordination in cadence or survey overlap, or would benefit from pixel-level co-processing that is beyond the scope of what is currently planned, rather than scientific programs that could be accomplished only at the catalog level without coordination in data processing or survey strategies. We provide two quantitative examples of scientific synergies: the decrease in photo-z errors (benefitting many science cases) when high resolution Euclid data are used for LSST photo-z determination, and the resulting increase in weak lensing signal-to-noise ratio from smaller photo-z errors. We briefly discuss other areas of coordination, including high performance computing resources and calibration data. Finally, we address concerns about the loss of independence and potential cross-checks between the two missions and potential consequences of not collaborating

Personalizing Survival Predictions in Advanced Colorectal Cancer: The ARCAD Nomogram Project.

Background Estimating prognosis on the basis of clinicopathologic factors can inform clinical practice and improve risk stratification for clinical trials. We constructed prognostic nomograms for one-year overall survival and six-month progression-free survival in metastatic colorectal carcinoma by using the ARCAD database. Methods Data from 22 674 patients in 26 randomized phase III clinical trials since 1997 were used to construct and validate Cox models, stratified by treatment arm within each study. Candidate variables included baseline age, sex, body mass index, performance status, colon vs rectal cancer, prior chemotherapy, number and location of metastatic sites, tumor mutation status (BRAF, KRAS), bilirubin, albumin, white blood cell count, hemoglobin, platelets, absolute neutrophil count, and derived neutrophil-to-lymphocyte ratio. Missing data (50% vs 50% vs < 50% probability] and actual [yes/no] overall and progression-free survival). Median survival predictions fell within the actual 95% Kaplan-Meier confidence intervals. Conclusions The nomograms are well calibrated and internally and externally valid. They have the potential to aid prognostication and patient-physician communication and balance risk in colorectal cancer trials