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Large-scale deployment of a rice 6 K SNP array for genetics and breeding applications.

S-McCouch PubMed Feed - Fri, 09/01/2017 - 07:36

Large-scale deployment of a rice 6 K SNP array for genetics and breeding applications.

Rice (N Y). 2017 Aug 30;10(1):40

Authors: Thomson MJ, Singh N, Dwiyanti MS, Wang DR, Wright MH, Perez FA, DeClerck G, Chin JH, Malitic-Layaoen GA, Juanillas VM, Dilla-Ermita CJ, Mauleon R, Kretzschmar T, McCouch SR

Abstract
BACKGROUND: Fixed arrays of single nucleotide polymorphism (SNP) markers have advantages over reduced representation sequencing in their ease of data analysis, consistently higher call rates, and rapid turnaround times. A 6 K SNP array represents a cost-benefit "sweet spot" for routine genetics and breeding applications in rice. Selection of informative SNPs across species and subpopulations during chip design is essential to obtain useful polymorphism rates for target germplasm groups. This paper summarizes results from large-scale deployment of an Illumina 6 K SNP array for rice.
RESULTS: Design of the Illumina Infinium 6 K SNP chip for rice, referred to as the Cornell_6K_Array_Infinium_Rice (C6AIR), includes 4429 SNPs from re-sequencing data and 1571 SNP markers from previous BeadXpress 384-SNP sets, selected based on polymorphism rate and allele frequency within and between target germplasm groups. Of the 6000 attempted bead types, 5274 passed Illumina's production quality control. The C6AIR was widely deployed at the International Rice Research Institute (IRRI) for genetic diversity analysis, QTL mapping, and tracking introgressions and was intensively used at Cornell University for QTL analysis and developing libraries of interspecific chromosome segment substitution lines (CSSLs) between O. sativa and diverse accessions of O. rufipogon or O. meridionalis. Collectively, the array was used to genotype over 40,000 rice samples. A set of 4606 SNP markers was used to provide high quality data for O. sativa germplasm, while a slightly expanded set of 4940 SNPs was used for O. sativa X O. rufipogon populations. Biparental polymorphism rates were generally between 1900 and 2500 well-distributed SNP markers for indica x japonica or interspecific populations and between 1300 and 1500 markers for crosses within indica, while polymorphism rates were lower for pairwise crosses within U.S. tropical japonica germplasm. Recently, a second-generation array containing ~7000 SNP markers, referred to as the C7AIR, was designed by removing poor-performing SNPs from the C6AIR and adding markers selected to increase the utility of the array for elite tropical japonica material.
CONCLUSIONS: The C6AIR has been successfully used to generate rapid and high-quality genotype data for diverse genetics and breeding applications in rice, and provides the basis for an optimized design in the C7AIR.

PMID: 28856618 [PubMed]

Large-scale deployment of a rice 6 K SNP array for genetics and breeding applications.

GDeClerck_pubmed - Fri, 09/01/2017 - 07:36

Large-scale deployment of a rice 6 K SNP array for genetics and breeding applications.

Rice (N Y). 2017 Aug 30;10(1):40

Authors: Thomson MJ, Singh N, Dwiyanti MS, Wang DR, Wright MH, Perez FA, DeClerck G, Chin JH, Malitic-Layaoen GA, Juanillas VM, Dilla-Ermita CJ, Mauleon R, Kretzschmar T, McCouch SR

Abstract
BACKGROUND: Fixed arrays of single nucleotide polymorphism (SNP) markers have advantages over reduced representation sequencing in their ease of data analysis, consistently higher call rates, and rapid turnaround times. A 6 K SNP array represents a cost-benefit "sweet spot" for routine genetics and breeding applications in rice. Selection of informative SNPs across species and subpopulations during chip design is essential to obtain useful polymorphism rates for target germplasm groups. This paper summarizes results from large-scale deployment of an Illumina 6 K SNP array for rice.
RESULTS: Design of the Illumina Infinium 6 K SNP chip for rice, referred to as the Cornell_6K_Array_Infinium_Rice (C6AIR), includes 4429 SNPs from re-sequencing data and 1571 SNP markers from previous BeadXpress 384-SNP sets, selected based on polymorphism rate and allele frequency within and between target germplasm groups. Of the 6000 attempted bead types, 5274 passed Illumina's production quality control. The C6AIR was widely deployed at the International Rice Research Institute (IRRI) for genetic diversity analysis, QTL mapping, and tracking introgressions and was intensively used at Cornell University for QTL analysis and developing libraries of interspecific chromosome segment substitution lines (CSSLs) between O. sativa and diverse accessions of O. rufipogon or O. meridionalis. Collectively, the array was used to genotype over 40,000 rice samples. A set of 4606 SNP markers was used to provide high quality data for O. sativa germplasm, while a slightly expanded set of 4940 SNPs was used for O. sativa X O. rufipogon populations. Biparental polymorphism rates were generally between 1900 and 2500 well-distributed SNP markers for indica x japonica or interspecific populations and between 1300 and 1500 markers for crosses within indica, while polymorphism rates were lower for pairwise crosses within U.S. tropical japonica germplasm. Recently, a second-generation array containing ~7000 SNP markers, referred to as the C7AIR, was designed by removing poor-performing SNPs from the C6AIR and adding markers selected to increase the utility of the array for elite tropical japonica material.
CONCLUSIONS: The C6AIR has been successfully used to generate rapid and high-quality genotype data for diverse genetics and breeding applications in rice, and provides the basis for an optimized design in the C7AIR.

PMID: 28856618 [PubMed]

Functional properties of an alternative, tissue-specific promoter for rice NADPH-dependent dihydroflavonol reductase.

S-McCouch PubMed Feed - Sat, 08/26/2017 - 08:20

Functional properties of an alternative, tissue-specific promoter for rice NADPH-dependent dihydroflavonol reductase.

PLoS One. 2017;12(8):e0183722

Authors: Kim J, Lee HJ, Jung YJ, Kang KK, Tyagi W, Kovach M, Sweeney M, McCouch S, Cho YG

Abstract
NADPH-dependent dihydroflavonol reductase (DFR) plays an important role in both anthocyanin biosynthesis and proanthocyanidin synthesis in plants. A specific and quantitative RT-PCR assay for transcription from the DFR promoter detected high expression with limited variability in rice tissues. A 440 bp minimal promoter region was identified by transfection of β-glucuronidase (GUS) reporter constructs into Jeokjinju variety. Alignment of the region with orthologous promoters revealed three conserved segments containing both bHLH (-386 to -381) and Myb (-368 to -362) binding sites. Transfection of β-glucuronidase constructs with targeted point mutations in the minimal promoter defined two sites important for promoter function to the transcription factor binding consensus sequences. The expression study showed that the bHLH binding domain (-386 to -381) is essential for DFR expression, and that a Myb binding domain (-368 to -362) is also required for full expression of the DFR gene, while the two bHLH binding domains (-104 to -99 and -27 to -22) nearest to the transcriptional start site are not necessary for DFR expression.

PMID: 28841686 [PubMed - in process]

Metabolomics and genomics combine to unravel the pathway for the presence of fragrance in rice.

S-McCouch PubMed Feed - Sun, 08/20/2017 - 06:26

Metabolomics and genomics combine to unravel the pathway for the presence of fragrance in rice.

Sci Rep. 2017 Aug 18;7(1):8767

Authors: Daygon VD, Calingacion M, Forster LC, Voss JJ, Schwartz BD, Ovenden B, Alonso DE, McCouch SR, Garson MJ, Fitzgerald MA

Abstract
Since it was first characterised in 1983, 2-acetyl-1-pyrroline (2AP) has been considered to be the most important aroma compound in rice. In this study, we show four other amine heterocycles: 6-methyl, 5-oxo-2,3,4,5-tetrahydropyridine (6M5OTP), 2-acetylpyrrole, pyrrole and 1-pyrroline, that correlate strongly with the production of 2AP, and are present in consistent proportions in a set of elite aromatic rice varieties from South East Asia and Australia as well as in a collection of recombinant inbred lines (RILs) derived from indica Jasmine-type varieties, Australian long grain varieties (temperate japonica) and Basmati-type rice (Grp V). These compounds were detected through untargeted metabolite profiling by two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF-MS), and their identity were confirmed by comparison with authentic standards analysed using gas chromatography mass spectrometry (GC-MS) and High Resolution GC × GC-TOF-MS (GC × GC HRT-4D). Genome-wide association analysis indicates that all compounds co-localised with a single quantitative trait locus (QTL) that harbours the FGR gene responsible for the production of GABA. Together, these data provide new insights into the production of 2AP, and evidence for understanding the pathway leading to the accumulation of aroma in fragrant rice.

PMID: 28821745 [PubMed - in process]

Hybrid assembly with long and short reads improves discovery of gene family expansions.

S-McCouch PubMed Feed - Fri, 07/21/2017 - 07:13
Related Articles

Hybrid assembly with long and short reads improves discovery of gene family expansions.

BMC Genomics. 2017 Jul 19;18(1):541

Authors: Miller JR, Zhou P, Mudge J, Gurtowski J, Lee H, Ramaraj T, Walenz BP, Liu J, Stupar RM, Denny R, Song L, Singh N, Maron LG, McCouch SR, McCombie WR, Schatz MC, Tiffin P, Young ND, Silverstein KAT

Abstract
BACKGROUND: Long-read and short-read sequencing technologies offer competing advantages for eukaryotic genome sequencing projects. Combinations of both may be appropriate for surveys of within-species genomic variation.
METHODS: We developed a hybrid assembly pipeline called "Alpaca" that can operate on 20X long-read coverage plus about 50X short-insert and 50X long-insert short-read coverage. To preclude collapse of tandem repeats, Alpaca relies on base-call-corrected long reads for contig formation.
RESULTS: Compared to two other assembly protocols, Alpaca demonstrated the most reference agreement and repeat capture on the rice genome. On three accessions of the model legume Medicago truncatula, Alpaca generated the most agreement to a conspecific reference and predicted tandemly repeated genes absent from the other assemblies.
CONCLUSION: Our results suggest Alpaca is a useful tool for investigating structural and copy number variation within de novo assemblies of sampled populations.

PMID: 28724409 [PubMed - in process]

The buffering capacity of stems: genetic architecture of nonstructural carbohydrates in cultivated Asian rice, Oryza sativa.

S-McCouch PubMed Feed - Wed, 05/31/2017 - 06:24

The buffering capacity of stems: genetic architecture of nonstructural carbohydrates in cultivated Asian rice, Oryza sativa.

New Phytol. 2017 May 30;:

Authors: Wang DR, Han R, Wolfrum EJ, McCouch SR

Abstract
Harnessing stem carbohydrate dynamics in grasses offers an opportunity to help meet future demands for plant-based food, fiber and fuel production, but requires a greater understanding of the genetic controls that govern the synthesis, interconversion and transport of such energy reserves. We map out a blueprint of the genetic architecture of rice (Oryza sativa) stem nonstructural carbohydrates (NSC) at two critical developmental time-points using a subpopulation-specific genome-wide association approach on two diverse germplasm panels followed by quantitative trait loci (QTL) mapping in a biparental population. Overall, 26 QTL are identified; three are detected in multiple panels and are associated with starch-at-maturity, sucrose-at-maturity and NSC-at-heading. They tag OsHXK6 (rice hexokinase), ISA2 (rice isoamylase) and a tandem array of sugar transporters. This study provides the foundation for more in-depth molecular investigation to validate candidate genes underlying rice stem NSC and informs future comparative studies in other agronomically vital grass species.

PMID: 28556941 [PubMed - as supplied by publisher]

Erratum to: Population dynamics among six major groups of the Oryza rufipogon species complex, wild relative of cultivated Asian rice.

S-McCouch PubMed Feed - Fri, 04/28/2017 - 06:50
Related Articles

Erratum to: Population dynamics among six major groups of the Oryza rufipogon species complex, wild relative of cultivated Asian rice.

Rice (N Y). 2017 Dec;10(1):17

Authors: Kim H, Jung J, Singh N, Greenberg A, Doyle JJ, Tyagi W, Chung JW, Kimball J, Hamilton RS, McCouch SR

PMID: 28447321 [PubMed - in process]

Genetic architecture of cold tolerance in rice (Oryza sativa) determined through high resolution genome-wide analysis.

S-McCouch PubMed Feed - Sat, 03/11/2017 - 08:52
Related Articles

Genetic architecture of cold tolerance in rice (Oryza sativa) determined through high resolution genome-wide analysis.

PLoS One. 2017;12(3):e0172133

Authors: Shakiba E, Edwards JD, Jodari F, Duke SE, Baldo AM, Korniliev P, McCouch SR, Eizenga GC

Abstract
Cold temperature is an important abiotic stress which negatively affects morphological development and seed production in rice (Oryza sativa L.). At the seedling stage, cold stress causes poor germination, seedling injury and poor stand establishment; and at the reproductive stage cold decreases seed yield. The Rice Diversity Panel 1 (RDP1) is a global collection of over 400 O. sativa accessions representing the five major subpopulations from the INDICA and JAPONICA varietal groups, with a genotypic dataset consisting of 700,000 SNP markers. The objectives of this study were to evaluate the RDP1 accessions for the complex, quantitatively inherited cold tolerance traits at the germination and reproductive stages, and to conduct genome-wide association (GWA) mapping to identify SNPs and candidate genes associated with cold stress at these stages. GWA mapping of the germination index (calculated as percent germination in cold divided by warm treatment) revealed 42 quantitative trait loci (QTLs) associated with cold tolerance at the seedling stage, including 18 in the panel as a whole, seven in temperate japonica, six in tropical japonica, 14 in JAPONICA, and nine in INDICA, with five shared across all subpopulations. Twenty-two of these QTLs co-localized with 32 previously reported cold tolerance QTLs. GWA mapping of cold tolerance at the reproductive stage detected 29 QTLs, including seven associated with percent sterility, ten with seed weight per panicle, 14 with seed weight per plant and one region overlapping for two traits. Fifteen co-localized with previously reported QTLs for cold tolerance or yield components. Candidate gene ontology searches revealed these QTLs were associated with significant enrichment for genes related to with lipid metabolism, response to stimuli, response to biotic stimuli (suggesting cross-talk between biotic and abiotic stresses), and oxygen binding. Overall the JAPONICA accessions were more tolerant to cold stress than INDICA accessions.

PMID: 28282385 [PubMed - in process]

Population Dynamics Among six Major Groups of the Oryza rufipogon Species Complex, Wild Relative of Cultivated Asian Rice.

S-McCouch PubMed Feed - Thu, 10/13/2016 - 08:02
Related Articles

Population Dynamics Among six Major Groups of the Oryza rufipogon Species Complex, Wild Relative of Cultivated Asian Rice.

Rice (N Y). 2016 Dec;9(1):56

Authors: Kim H, Jung J, Singh N, Greenberg A, Doyle JJ, Tyagi W, Chung JW, Kimball J, Hamilton RS, McCouch SR

Abstract
BACKGROUND: Understanding population structure of the wild progenitor of Asian cultivated rice (O. sativa), the Oryza rufipogon species complex (ORSC), is of interest to plant breeders and contributes to our understanding of rice domestication. A collection of 286 diverse ORSC accessions was evaluated for nuclear variation using genotyping-by-sequencing (113,739 SNPs) and for chloroplast variation using Sanger sequencing (25 polymorphic sites).
RESULTS: Six wild subpopulations were identified, with 25 % of accessions classified as admixed. Three of the wild groups were genetically and geographically closely related to the O. sativa subpopulations, indica, aus and japonica, and carried O. sativa introgressions; the other three wild groups were genetically divergent, had unique chloroplast haplotypes, and were located at the geographical extremes of the species range. The genetic subpopulations were significantly correlated (r (2) = 0.562) with traditional species designations, O. rufipogon (perennial) and O. nivara (annual), differentiated based on morphology and life history. A wild diversity panel of 95 purified (inbred) accessions was developed for future genetic studies.
CONCLUSIONS: Our results suggest that the cultivated aus subpopulation is most closely related to an annual wild relative, japonica to a perennial wild relative, and indica to an admixed population of diverse annual and perennial wild ancestors. Gene flow between ORSC and O. sativa is common in regions where rice is cultivated, threatening the identity and diversity of wild ORSC populations. The three geographically isolated ORSC populations harbor variation rarely seen in cultivated rice and provide a unique window into the genetic composition of ancient rice subpopulations.

PMID: 27730519 [PubMed - in process]

When more is better: how data sharing would accelerate genomic selection of crop plants.

S-McCouch PubMed Feed - Sat, 10/08/2016 - 10:13
Related Articles

When more is better: how data sharing would accelerate genomic selection of crop plants.

New Phytol. 2016 Sep 26;:

Authors: Spindel JE, McCouch SR

Abstract
Genomic selection is proving an effective new strategy for increasing breeding efficiency in a wide variety of cereal species - the staple crops that feed the world. A preponderance of studies, reviewed here, has confirmed that the more correlated phenotypic and environmental data that are used to feed genomics-assisted breeding models, the better the prediction accuracies of the models and the more useful the breeding outcomes. We argue that based on these empirical results, new alliances to share data across genomic selection breeding programs are critical to the rapid development and deployment of new crop varieties.

PMID: 27716975 [PubMed - as supplied by publisher]

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice.

S-McCouch PubMed Feed - Fri, 10/07/2016 - 08:02
Related Articles

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice.

J Exp Bot. 2016 Oct 5;:

Authors: Wang DR, Wolfrum EJ, Virk P, Ismail A, Greenberg AJ, McCouch SR

Abstract
Rice plants (Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, established an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. We find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice.

PMID: 27707775 [PubMed - as supplied by publisher]

Whole-genome characterization in pedigreed non-human primates using genotyping-by-sequencing (GBS) and imputation.

S-McCouch PubMed Feed - Fri, 08/26/2016 - 08:24

Whole-genome characterization in pedigreed non-human primates using genotyping-by-sequencing (GBS) and imputation.

BMC Genomics. 2016;17:676

Authors: Bimber BN, Raboin MJ, Letaw J, Nevonen KA, Spindel JE, McCouch SR, Cervera-Juanes R, Spindel E, Carbone L, Ferguson B, Vinson A

Abstract
BACKGROUND: Rhesus macaques are widely used in biomedical research, but the application of genomic information in this species to better understand human disease is still in its infancy. Whole-genome sequence (WGS) data in large pedigreed macaque colonies could provide substantial experimental power for genetic discovery, but the collection of WGS data in large cohorts remains a formidable expense. Here, we describe a cost-effective approach that selects the most informative macaques in a pedigree for 30X WGS, followed by low-cost genotyping-by-sequencing (GBS) at 30X on the remaining macaques in order to generate sparse genotype data at high accuracy. Dense variants from the selected macaques with WGS data are then imputed into macaques having only sparse GBS data, resulting in dense genome-wide genotypes throughout the pedigree.
RESULTS: We developed GBS for the macaque genome using a digestion with PstI, followed by sequencing of size-selected fragments at 30X coverage. From GBS sequence data collected on all individuals in a 16-member pedigree, we characterized high-confidence genotypes at 22,455 single nucleotide variant (SNV) sites that were suitable for guiding imputation of dense sequence data from WGS. To characterize dense markers for imputation, we performed WGS at 30X coverage on nine of the 16 individuals, yielding 10,193,425 high-confidence SNVs. To validate the use of GBS data for facilitating imputation, we initially focused on chromosome 19 as a test case, using an optimized panel of 833 sparse, evenly-spaced markers from GBS and 5,010 dense markers from WGS. Using the method of "Genotype Imputation Given Inheritance" (GIGI), we evaluated the effects on imputation accuracy of 3 different strategies for selecting individuals for WGS, including 1) using "GIGI-Pick" to select the most informative individuals, 2) using the most recent generation, or 3) using founders only.  We also evaluated the effects on imputation accuracy of using a range of from 1 to 9 WGS individuals for imputation. We found that the GIGI-Pick algorithm for selection of WGS individuals outperformed common heuristic approaches, and that genotype numbers and accuracy improved very little when using >5 WGS individuals for imputation. Informed by our findings, we used 4 macaques with WGS data to impute variants at up to 7,655,491 sites spanning all 20 autosomes in the 12 remaining macaques, based on their GBS genotypes at only 17,158 loci. Using a strict confidence threshold, we imputed an average of 3,680,238 variants per individual at >99 % accuracy, or an average 4,458,883 variants per individual at a more relaxed threshold, yielding >97 % accuracy.
CONCLUSIONS: We conclude that an optimal tradeoff between genotype accuracy, number of imputed genotypes, and overall cost exists at the ratio of one individual selected for WGS using the GIGI-Pick algorithm, per 3-5 relatives selected for GBS. This approach makes feasible the collection of accurate, dense genome-wide sequence data in large pedigreed macaque cohorts without the need for more expensive WGS data on all individuals.

PMID: 27558348 [PubMed - in process]

Loss of function at RAE2, a previously unidentified EPFL, is required for awnlessness in cultivated Asian rice.

S-McCouch PubMed Feed - Fri, 07/29/2016 - 06:48

Loss of function at RAE2, a previously unidentified EPFL, is required for awnlessness in cultivated Asian rice.

Proc Natl Acad Sci U S A. 2016 Jul 27;

Authors: Bessho-Uehara K, Wang DR, Furuta T, Minami A, Nagai K, Gamuyao R, Asano K, Angeles-Shim RB, Shimizu Y, Ayano M, Komeda N, Doi K, Miura K, Toda Y, Kinoshita T, Okuda S, Higashiyama T, Nomoto M, Tada Y, Shinohara H, Matsubayashi Y, Greenberg A, Wu J, Yasui H, Yoshimura A, Mori H, McCouch SR, Ashikari M

Abstract
Domestication of crops based on artificial selection has contributed numerous beneficial traits for agriculture. Wild characteristics such as red pericarp and seed shattering were lost in both Asian (Oryza sativa) and African (Oryza glaberrima) cultivated rice species as a result of human selection on common genes. Awnedness, in contrast, is a trait that has been lost in both cultivated species due to selection on different sets of genes. In a previous report, we revealed that at least three loci regulate awn development in rice; however, the molecular mechanism underlying awnlessness remains unknown. Here we isolate and characterize a previously unidentified EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family member named REGULATOR OF AWN ELONGATION 2 (RAE2) and identify one of its requisite processing enzymes, SUBTILISIN-LIKE PROTEASE 1 (SLP1). The RAE2 precursor is specifically cleaved by SLP1 in the rice spikelet, where the mature RAE2 peptide subsequently induces awn elongation. Analysis of RAE2 sequence diversity identified a highly variable GC-rich region harboring multiple independent mutations underlying protein-length variation that disrupt the function of the RAE2 protein and condition the awnless phenotype in Asian rice. Cultivated African rice, on the other hand, retained the functional RAE2 allele despite its awnless phenotype. Our findings illuminate the molecular function of RAE2 in awn development and shed light on the independent domestication histories of Asian and African cultivated rice.

PMID: 27466405 [PubMed - as supplied by publisher]

OntoADR a Semantic Resource Describing Adverse Drug Reactions to Support Searching, Coding, and Information Retrieval.

GDeClerck_pubmed - Sun, 07/03/2016 - 08:46

OntoADR a Semantic Resource Describing Adverse Drug Reactions to Support Searching, Coding, and Information Retrieval.

J Biomed Inform. 2016 Jun 28;

Authors: Souvignet J, Declerck G, Asfari H, Jaulent MC, Bousquet C

Abstract
INTRODUCTION: Efficient searching and coding in databases that use terminological resources requires that they support efficient data retrieval. The Medical Dictionary for Regulatory Activities (MedDRA) is a reference terminology for several countries and organizations to code adverse drug reactions (ADRs) for pharmacovigilance. Ontologies that are available in the medical domain provide several advantages such as reasoning to improve data retrieval. The field of pharmacovigilance does not yet benefit from a fully operational ontology to formally represent the MedDRA terms. Our objective was to build a semantic resource based on formal description logic to improve MedDRA term retrieval and aid the generation of on-demand custom groupings by appropriately and efficiently selecting terms: OntoADR.
METHODS: The method consists of the following steps: 1) mapping between MedDRA terms and SNOMED-CT, 2) generation of semantic definitions using semi-automatic methods, 3) storage of the resource and 4) manual curation by pharmacovigilance experts.
RESULTS: We built a semantic resource for ADRs enabling a new type of semantics-based term search. OntoADR adds new search capabilities relative to previous approaches, overcoming the usual limitations of computation using lightweight description logic, such as the intractability of unions or negation queries, bringing it closer to user needs. Our automated approach for defining MedDRA terms enabled the association of at least one defining relationship with 67% of preferred terms. The curation work performed on our sample showed an error level of 14% for this automated approach. We tested OntoADR in practice, which allowed us to build custom groupings for several medical topics of interest.
DISCUSSION: The methods we describe in this article could be adapted and extended to other terminologies which do not benefit from a formal semantic representation, thus enabling better data retrieval performance. Our custom groupings of MedDRA terms were used while performing signal detection, which suggests that the graphical user interface we are currently implementing to process OntoADR could be usefully integrated into specialized pharmacovigilance software that rely on MedDRA.

PMID: 27369567 [PubMed - as supplied by publisher]

MedDRA® Automated Term Groupings using OntoADR: Evaluation with Upper Gastrointestinal Bleedings.

GDeClerck_pubmed - Tue, 06/28/2016 - 09:50
Related Articles

MedDRA® Automated Term Groupings using OntoADR: Evaluation with Upper Gastrointestinal Bleedings.

Expert Opin Drug Saf. 2016 Jun 27;

Authors: Souvignet J, Asfari H, Lardon J, Del Tedesco E, Declerck G, Bousquet C

Abstract
OBJECTIVE: To propose a method to build customized sets of MedDRA (MedDRA® is a registered trademark of the International Federation of Pharmaceutical Manufacturers and Associations.) terms when no appropriate grouping is available for the description of a medical condition. We illustrate this method with upper gastrointestinal bleedings (UGIB). In MedDRA, there is a dedicated SMQ for gastrointestinal hemorrhages but it does not allow users to distinguish between adverse drug reactions (ADRs) related to the upper or lower part of the digestive tract structure.
RESEARCH DESIGN AND METHODS: We created a broad list of MedDRA terms related to UGIB and defined a gold standard with the help of experts. MedDRA terms were formally described in a semantic resource named OntoADR. We report the use of two semantic queries that automatically select candidate terms for UGIB. Query 1 is a combination of two SNOMED CT concepts describing both morphology "Hemorrhage" and finding site "Upper digestive tract structure". Query 2 complements Query 1 by taking into account additional MedDRA terms associated to two SNOMED CT concepts describing clinical manifestations "Melena" or "Hematemesis".
RESULTS: We compared terms in queries and our gold standard achieving a recall of 71.0% and a precision of 81.4% for query 1 (F1 score 0.76); and a recall of 96.7% and a precision of 77.0% for query 2 (F1 score 0.86).
CONCLUSIONS: Our results demonstrate the feasibility of applying knowledge engineering techniques for building customized sets of MedDRA terms. Additional work is necessary on OntoADR to improve precision and recall and further evaluation on additional medical conditions should confirm the interest of the proposed strategy.

PMID: 27348725 [PubMed - as supplied by publisher]

Genome-Wide Association Study for Traits Related to Plant and Grain Morphology, and Root Architecture in Temperate Rice Accessions.

S-McCouch PubMed Feed - Fri, 05/27/2016 - 08:05
Related Articles

Genome-Wide Association Study for Traits Related to Plant and Grain Morphology, and Root Architecture in Temperate Rice Accessions.

PLoS One. 2016;11(5):e0155425

Authors: Biscarini F, Cozzi P, Casella L, Riccardi P, Vattari A, Orasen G, Perrini R, Tacconi G, Tondelli A, Biselli C, Cattivelli L, Spindel J, McCouch S, Abbruscato P, Valé G, Piffanelli P, Greco R

Abstract
BACKGROUND: In this study we carried out a genome-wide association analysis for plant and grain morphology and root architecture in a unique panel of temperate rice accessions adapted to European pedo-climatic conditions. This is the first study to assess the association of selected phenotypic traits to specific genomic regions in the narrow genetic pool of temperate japonica. A set of 391 rice accessions were GBS-genotyped yielding-after data editing-57000 polymorphic and informative SNPS, among which 54% were in genic regions.
RESULTS: In total, 42 significant genotype-phenotype associations were detected: 21 for plant morphology traits, 11 for grain quality traits, 10 for root architecture traits. The FDR of detected associations ranged from 3 · 10-7 to 0.92 (median: 0.25). In most cases, the significant detected associations co-localised with QTLs and candidate genes controlling the phenotypic variation of single or multiple traits. The most significant associations were those for flag leaf width on chromosome 4 (FDR = 3 · 10-7) and for plant height on chromosome 6 (FDR = 0.011).
CONCLUSIONS: We demonstrate the effectiveness and resolution of the developed platform for high-throughput phenotyping, genotyping and GWAS in detecting major QTLs for relevant traits in rice. We identified strong associations that may be used for selection in temperate irrigated rice breeding: e.g. associations for flag leaf width, plant height, root volume and length, grain length, grain width and their ratio. Our findings pave the way to successfully exploit the narrow genetic pool of European temperate rice and to pinpoint the most relevant genetic components contributing to the adaptability and high yield of this germplasm. The generated data could be of direct use in genomic-assisted breeding strategies.

PMID: 27228161 [PubMed - as supplied by publisher]

Corrigendum: Open access resources for genome-wide association mapping in rice.

S-McCouch PubMed Feed - Thu, 04/21/2016 - 08:24
Related Articles

Corrigendum: Open access resources for genome-wide association mapping in rice.

Nat Commun. 2016;7:11346

Authors: McCouch SR, Wright MH, Tung CW, Maron LG, McNally KL, Fitzgerald M, Singh N, DeClerck G, Perez FA, Korniliev P, Greenberg AJ, Naredo ME, Mercado SM, Harrington SE, Shi Y, Branchini DA, Kuser-Falcão PR, Leung H, Ebana K, Yano M, Eizenga G, McClung A, Mezey J

PMID: 27094317 [PubMed - in process]

Corrigendum: Open access resources for genome-wide association mapping in rice.

GDeClerck_pubmed - Thu, 04/21/2016 - 08:24
Related Articles

Corrigendum: Open access resources for genome-wide association mapping in rice.

Nat Commun. 2016;7:11346

Authors: McCouch SR, Wright MH, Tung CW, Maron LG, McNally KL, Fitzgerald M, Singh N, DeClerck G, Perez FA, Korniliev P, Greenberg AJ, Naredo ME, Mercado SM, Harrington SE, Shi Y, Branchini DA, Kuser-Falcão PR, Leung H, Ebana K, Yano M, Eizenga G, McClung A, Mezey J

PMID: 27094317 [PubMed - in process]

Evidence for divergence of response in Indica, Japonica, and wild rice to high CO2 x temperature interaction.

S-McCouch PubMed Feed - Thu, 03/10/2016 - 08:46
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Evidence for divergence of response in Indica, Japonica, and wild rice to high CO2 x temperature interaction.

Glob Chang Biol. 2016 Mar 9;

Authors: Wang DR, Bunce JA, Tomecek MB, Gealy D, McClung A, McCouch SR, Ziska LH

Abstract
High CO2 and high temperature have an antagonistic interaction effect on rice yield potential and present a unique challenge to adapting rice to projected future climates. Understanding how the differences in response to these two abiotic variables are partitioned across rice germplasm accessions may be key to identifying potentially useful sources of resilient alleles for adapting rice to climate change. In this study, we evaluated eleven globally diverse rice accessions under controlled conditions at two carbon dioxide concentrations (400 and 600 ppm) and four temperature environments (29°C day/21°C night; 29°C day/21°C night with additional heat stress at anthesis; 34°C day/26°C night; and 34°C day/26°C night with additional heat stress at anthesis) for a suite of traits including five yield components, five growth characteristics, one phenological trait, and four photosynthesis-related measurements. Multivariate analyses of mean trait data from these eight treatments divide our rice panel into two primary groups consistent with the genetic classification of INDICA/INDICA-like and JAPONICA populations. Overall, we find that the productivity of plants grown under elevated [CO2 ] was more sensitive (negative response) to high temperature stress compared with that of plants grown under ambient [CO2 ] across this diversity panel. We report differential response to CO2 x temperature interaction for INDICA/INDICA-like and JAPONICA rice accessions and find preliminary evidence for the beneficial introduction of exotic alleles into cultivated rice genomic background. Overall, these results support the idea of using wild or currently unadapted gene pools in rice to enhance breeding efforts to secure future climate change adaptation. This article is protected by copyright. All rights reserved.

PMID: 26959982 [PubMed - as supplied by publisher]

Genome-wide prediction models that incorporate de novo GWAS are a powerful new tool for tropical rice improvement.

S-McCouch PubMed Feed - Thu, 02/11/2016 - 08:59
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Genome-wide prediction models that incorporate de novo GWAS are a powerful new tool for tropical rice improvement.

Heredity (Edinb). 2016 Feb 10;

Authors: Spindel JE, Begum H, Akdemir D, Collard B, Redoña E, Jannink JL, McCouch S

Abstract
To address the multiple challenges to food security posed by global climate change, population growth and rising incomes, plant breeders are developing new crop varieties that can enhance both agricultural productivity and environmental sustainability. Current breeding practices, however, are unable to keep pace with demand. Genomic selection (GS) is a new technique that helps accelerate the rate of genetic gain in breeding by using whole-genome data to predict the breeding value of offspring. Here, we describe a new GS model that combines RR-BLUP with markers fit as fixed effects selected from the results of a genome-wide-association study (GWAS) on the RR-BLUP training data. We term this model GS + de novo GWAS. In a breeding population of tropical rice, GS + de novo GWAS outperformed six other models for a variety of traits and in multiple environments. On the basis of these results, we propose an extended, two-part breeding design that can be used to efficiently integrate novel variation into elite breeding populations, thus expanding genetic diversity and enhancing the potential for sustainable productivity gains.Heredity advance online publication, 10 February 2016; doi:10.1038/hdy.2015.113.

PMID: 26860200 [PubMed - as supplied by publisher]

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