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

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]

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

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.

Tue, 06/28/2016 - 09:50
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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]

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

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]

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

Fri, 02/05/2016 - 06:18
Related Articles

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

Nat Commun. 2016;7:10532

Authors: McCouch SR, Wright MH, Tung CW, Maron LG, McNally KL, Fitzgerald M, Singh N, DeClerck G, Agosto-Perez F, 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

Abstract
Increasing food production is essential to meet the demands of a growing human population, with its rising income levels and nutritional expectations. To address the demand, plant breeders seek new sources of genetic variation to enhance the productivity, sustainability and resilience of crop varieties. Here we launch a high-resolution, open-access research platform to facilitate genome-wide association mapping in rice, a staple food crop. The platform provides an immortal collection of diverse germplasm, a high-density single-nucleotide polymorphism data set tailored for gene discovery, well-documented analytical strategies, and a suite of bioinformatics resources to facilitate biological interpretation. Using grain length, we demonstrate the power and resolution of our new high-density rice array, the accompanying genotypic data set, and an expanded diversity panel for detecting major and minor effect QTLs and subpopulation-specific alleles, with immediate implications for rice improvement.

PMID: 26842267 [PubMed - in process]

How we remember what we can do.

Thu, 10/29/2015 - 06:20

How we remember what we can do.

Socioaffect Neurosci Psychol. 2015;5:24807

Authors: Declerck G

Abstract
According to the motor simulation theory, the knowledge we possess of what we can do is based on simulation mechanisms triggered by an off-line activation of the brain areas involved in motor control. Action capabilities memory does not work by storing some content, but consists in the capacity, rooted in sensory-motor systems, to reenact off-line action sequences exhibiting the range of our powers. In this paper, I present several arguments from cognitive neuropsychology, but also first-person analysis of experience, against this hypothesis. The claim that perceptual access to affordances is mediated by motor simulation processes rests on a misunderstanding of what affordances are, and comes up against a computational reality principle. Motor simulation cannot provide access to affordances because (i) the affordances we are aware of at each moment are too many for their realization to be simulated by the brain and (ii) affordances are not equivalent to currently or personally feasible actions. The explanatory significance of the simulation theory must then be revised downwards compared to what is claimed by most of its advocates. One additional challenge is to determine the prerequisite, in terms of cognitive processing, for the motor simulation mechanisms to work. To overcome the limitations of the simulation theory, I propose a new approach: the direct content specification hypothesis. This hypothesis states that, at least for the most basic actions of our behavioral repertoire, the action possibilities we are aware of through perception are directly specified by perceptual variables characterizing the content of our experience. The cognitive system responsible for the perception of action possibilities is consequently far more direct, in terms of cognitive processing, than what is stated by the simulation theory. To support this hypothesis I review evidence from current neuropsychological research, in particular data suggesting a phenomenon of 'fossilization' of affordances. Fossilization can be defined as a gap between the capacities that are treated as available by the cognitive system and the capacities this system really has at its disposal. These considerations do not mean that motor simulation cannot contribute to explain how we gain perceptual knowledge of what we can do based on the memory of our past performances. However, when precisely motor simulation plays a role and what it is for exactly currently remain largely unknown.

PMID: 26507953 [PubMed]

Bridging Data Models and Terminologies to Support Adverse Drug Event Reporting Using EHR Data.

Wed, 12/10/2014 - 08:25
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Bridging Data Models and Terminologies to Support Adverse Drug Event Reporting Using EHR Data.

Methods Inf Med. 2014 Dec 9;54(1)

Authors: Declerck G, Hussain S, Daniel C, Yuksel M, Laleci GB, Twagirumukiza M, Jaulent MC

PMID: 25487120 [PubMed - as supplied by publisher]

Describing Localized Diseases in Medical Ontology: An FMA-based Algorithm.

Thu, 08/28/2014 - 08:48
Related Articles

Describing Localized Diseases in Medical Ontology: An FMA-based Algorithm.

Stud Health Technol Inform. 2014;205:1023-1027

Authors: Charlet J, Mazuel L, Declerck G, Miroux P, Gayet P

Abstract
ONTOLURGENCES is a termino-ontological resource developed to index and retrieve information in electronic Emergency Medical Record. In this project, we improved the ontology coverage to accommodate both anatomical and pathophysiological concepts in emergency medicine. This work lead to the automatic addition of 3,470 concepts and their underlying semantic formalization. In our method, we reuse and select the anatomical concepts relevant to emergency from FMA: To capture the anatomical specific concepts, (i) we involved Emergency practitioners and identified the key concepts from this domain; (ii) we applied an automatic algorithm to define the semantic relationships and integrated the result in the existing ontology.

PMID: 25160343 [PubMed - as supplied by publisher]

Automatic annotation of ICD-to-MedDRA mappings with SKOS predicates.

Thu, 08/28/2014 - 08:48
Related Articles

Automatic annotation of ICD-to-MedDRA mappings with SKOS predicates.

Stud Health Technol Inform. 2014;205:1013-1017

Authors: Declerck G, Souvignet J, Rodrigues JM, Jaulent MC

Abstract
Robust alignments between ICD and MedDRA are essential to enable the secondary use of clinical data for pharmacovigilance research. UMLS makes available ICD-to-MedDRA mappings, but they are only poorly specified, which introduces difficulties when exploited in an automatic way. SKOS vocabulary can help achieve quality and machine-processable mappings. We have developed an algorithm based on several simple rules which annotates automatically ICD-to-MedDRA mappings with SKOS predicates. The method was tested and evaluated on a sample of ICD-10-to MedDRA mappings extracted from UMLS. The algorithm demonstrated satisfying performances, especially for skos:exactMatch properties, which suggests that automatic methods can be used to improve the quality of terminology mappings.

PMID: 25160341 [PubMed - as supplied by publisher]

Ci4SeR - Curation Interface for Semantic Resources - Evaluation with Adverse Drug Reactions.

Thu, 08/28/2014 - 08:48
Related Articles

Ci4SeR - Curation Interface for Semantic Resources - Evaluation with Adverse Drug Reactions.

Stud Health Technol Inform. 2014;205:116-120

Authors: Souvignet J, Asfari H, Declerck G, Lardon J, Trombert-Paviot B, Jaulent MC, Bousquet C

Abstract
Evaluation and validation have become a crucial problem for the development of semantic resources. We developed Ci4SeR, a Graphical User Interface to optimize the curation work (not taking into account structural aspects), suitable for any type of resource with lightweight description logic. We tested it on OntoADR, an ontology of adverse drug reactions. A single curator has reviewed 326 terms (1020 axioms) in an estimated time of 120 hours (2.71 concepts and 8.5 axioms reviewed per hour) and added 1874 new axioms (15.6 axioms per hour). Compared with previous manual endeavours, the interface allows increasing the speed-rate of reviewed concepts by 68% and axiom addition by 486%. A wider use of Ci4SeR would help semantic resources curation and improve completeness of knowledge modelling.

PMID: 25160157 [PubMed - as supplied by publisher]

Reasons (not) to Spend a Few Billions More on EHRs: How Human Factors Research Can Help.

Sat, 08/16/2014 - 06:09

Reasons (not) to Spend a Few Billions More on EHRs: How Human Factors Research Can Help.

Yearb Med Inform. 2014;9(1):90-6

Authors: Declerck G, Aimé X

Abstract
OBJECTIVES: To select best medical informatics research works published in 2013 on electronic health record (EHR) adoption, design, and impact, from the perspective of human factors and organizational issues (HFOI).
METHODS: We selected 2,764 papers by querying PubMed (Mesh and TIAB) as well as using a manual search. Papers were evaluated based on pre-defined exclusion and inclusion criteria from their title, keywords, and abstract to select 15 candidate best papers, finally reviewed by 4 external reviewers using a standard evaluation grid.
RESULTS: Five papers were selected as best papers to illustrate how human factors approaches can improve EHR adoption and design. Among other contributions, these works: (i) make use of the observational and analysis methodologies of social and cognitive sciences to understand clinicians' attitudes towards EHRs, EHR use patterns, and impact on care processes, workflows, information exchange, and coordination of care; (ii) take into account macro- (environmental) and meso- (organizational) level factors to analyze EHR adoption or lack thereof; (iii) highlight the need for qualitative studies to analyze the unexpected side effects of EHRs on cognitive and work processes as well as the persistent use of paper.
CONCLUSION: Selected papers tend to demonstrate that HFOI approaches and methodologies are essential to bridge the gap between EHR systems and end users, and to reduce regularly reported adoption failures and unexpected consequences.

PMID: 25123727 [PubMed - in process]

Formalizing MedDRA to support semantic reasoning on adverse drug reaction terms.

Tue, 04/01/2014 - 07:15

Formalizing MedDRA to support semantic reasoning on adverse drug reaction terms.

J Biomed Inform. 2014 Mar 25;

Authors: Bousquet C, Sadou E, Souvignet J, Jaulent MC, Declerck G

Abstract
Although MedDRA has obvious advantages over previous terminologies for coding adverse drug reactions and discovering potential signals using data mining techniques, its terminological organization constrains users to search terms according to predefined categories. Adding formal definitions to MedDRA would allow retrieval of terms according to a case definition that may correspond to novel categories that are not currently available in the terminology. To achieve semantic reasoning with MedDRA, we have associated formal definitions to MedDRA terms in an OWL file named OntoADR that is the result of our first step for providing an "ontologized" version of MedDRA. MedDRA five-levels original hierarchy was converted into a subsumption tree and formal definitions of MedDRA terms were designed using several methods: mappings to SNOMED-CT, semi-automatic definition algorithms or a fully manual way. This article presents the main steps of OntoADR conception process, its structure and content, and discusses problems and limits raised by this attempt to "ontologize" MedDRA.

PMID: 24680984 [PubMed - as supplied by publisher]

Why Medical Informatics (still) Needs Cognitive and Social Sciences.

Tue, 08/27/2013 - 08:33

Why Medical Informatics (still) Needs Cognitive and Social Sciences.

Yearb Med Inform. 2013;8(1):86-92

Authors: Declerck G, Aimé X, Section Editors for the IMIA Yearbook Section on Human Factors and Organizational Issues

Abstract
OBJECTIVES: To summarize current excellent medical informatics research in the field of human factors and organizational issues.
METHODS: Using PubMed, a total of 3,024 papers were selected from 17 journals. The papers were evaluated on the basis of their title, keywords, and abstract, using several exclusion and inclusion criteria. 15 preselected papers were carefully evaluated by six referees using a standard evaluation grid.
RESULTS: Six best papers were selected exemplifying the central role cognitive and social sciences can play in medical informatics research. Among other contributions, those studies: (i) make use of the distributed cognition paradigm to model and understand clinical care situations; (ii) take into account organizational issues to analyse the impact of HIT on information exchange and coordination processes; (iii) illustrate how models and empirical data from cognitive psychology can be used in medical informatics; and (iv) highlight the need of qualitative studies to analyze the unexpected side effects of HIT on cognitive and work processes.
CONCLUSION: The selected papers demonstrate that paradigms, methodologies, models, and results from cognitive and social sciences can help to bridge the gap between HIT and end users, and contribute to limit adoption failures that are reported regularly.

PMID: 23974553 [PubMed - in process]

Building a time-saving and adaptable tool to report adverse drug events.

Thu, 08/08/2013 - 06:19

Building a time-saving and adaptable tool to report adverse drug events.

Stud Health Technol Inform. 2013;192:903-7

Authors: Parès Y, Declerck G, Hussain S, Ng R, Jaulent MC

Abstract
The difficult task of detecting adverse drug events (ADEs) and the tedious process of building manual reports of ADE occurrences out of patient profiles result in a majority of adverse reactions not being reported to health regulatory authorities. The SALUS individual case safety report (ICSR) reporting tool, a component currently developed within the SALUS project, aims to support semi-automatic reporting of ADEs to regulatory authorities. In this paper, we present an initial design and current state of of our ICSR reporting tool that features: (i) automatic pre-population of reporting forms through extraction of the patient data contained in an Electronic Health Record (EHR); (ii) generation and electronic submission of the completed ICSRs by the physician to regulatory authorities; and (iii) integration of the reporting process into the physician's work-flow to limit the disturbance. The objective is to increase the rates of ADE reporting and the quality of the reported data. The SALUS interoperability platform supports patient data extraction independently of the EHR data model in use and allows generation of reports using the format expected by regulatory authorities.

PMID: 23920689 [PubMed - in process]

PICARA, an analytical pipeline providing probabilistic inference about a priori candidates genes underlying genome-wide association QTL in plants.

Mon, 06/10/2013 - 12:45
Related Articles

PICARA, an analytical pipeline providing probabilistic inference about a priori candidates genes underlying genome-wide association QTL in plants.

PLoS One. 2012;7(11):e46596

Authors: Chen C, DeClerck G, Tian F, Spooner W, McCouch S, Buckler E

Abstract
PICARA is an analytical pipeline designed to systematically summarize observed SNP/trait associations identified by genome wide association studies (GWAS) and to identify candidate genes involved in the regulation of complex trait variation. The pipeline provides probabilistic inference about a priori candidate genes using integrated information derived from genome-wide association signals, gene homology, and curated gene sets embedded in pathway descriptions. In this paper, we demonstrate the performance of PICARA using data for flowering time variation in maize - a key trait for geographical and seasonal adaption of plants. Among 406 curated flowering time-related genes from Arabidopsis, we identify 61 orthologs in maize that are significantly enriched for GWAS SNP signals, including key regulators such as FT (Flowering Locus T) and GI (GIGANTEA), and genes centered in the Arabidopsis circadian pathway, including TOC1 (Timing of CAB Expression 1) and LHY (Late Elongated Hypocotyl). In addition, we discover a regulatory feature that is characteristic of these a priori flowering time candidates in maize. This new probabilistic analytical pipeline helps researchers infer the functional significance of candidate genes associated with complex traits and helps guide future experiments by providing statistical support for gene candidates based on the integration of heterogeneous biological information.

PMID: 23144785 [PubMed - indexed for MEDLINE]

Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype-phenotype relationships and its relevance to crop improvement.

Tue, 04/23/2013 - 05:45
Related Articles

Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype-phenotype relationships and its relevance to crop improvement.

Theor Appl Genet. 2013 Mar 8;

Authors: Cobb JN, Declerck G, Greenberg A, Clark R, McCouch S

Abstract
More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties.

PMID: 23471459 [PubMed - as supplied by publisher]

Automatic generation of MedDRA terms groupings using an ontology.

Sat, 03/09/2013 - 05:45
Related Articles

Automatic generation of MedDRA terms groupings using an ontology.

Stud Health Technol Inform. 2012;180:73-7

Authors: Declerck G, Bousquet C, Jaulent MC

Abstract
In the context of PROTECT European project, we have developed an ontology of adverse drug reactions (OntoADR) based on the original MedDRA hierarchy and a query-based method to achieve automatic MedDRA terms groupings for improving pharmacovigilance signal detection. Those groupings were evaluated against standard handmade MedDRA groupings corresponding to first priority pharmacovigilance safety topics. Our results demonstrate that this automatic method allows catching most of the terms present in the reference groupings, and suggest that it could offer an important saving of time for the achievement of pharmacovigilance groupings. This paper describes the theoretical context of this work, the evaluation methodology, and presents the principal results.

PMID: 22874155 [PubMed - indexed for MEDLINE]

Evaluation of automated term groupings for detecting anaphylactic shock signals for drugs.

Wed, 01/23/2013 - 05:45

Evaluation of automated term groupings for detecting anaphylactic shock signals for drugs.

AMIA Annu Symp Proc. 2012;2012:882-90

Authors: Souvignet J, Declerck G, Trombert B, Rodrigues JM, Jaulent MC, Bousquet C

Abstract
Signal detection in pharmacovigilance should take into account all terms related to a medical concept rather than a single term. We built an OWL-DL file with formal definitions of MedDRA and SNOMED-CT concepts and performed two queries, Query 1 and 2, to retrieve narrow and broad terms within the Standard MedDRA Query (SMQ) related to 'anaphylactic shock' and the terms from the High Level Term (HLT) grouping related to 'anaphylaxis'. We compared values of the EB05 (EBGM) statistical test for disproportionality with 50 active ingredients randomly selected in the public version of the FDA pharmacovigilance database. Coefficient of correlation was R(2) = 1.00 between Query 1 and HLT; R(2) = 0.98 between Query 1 and SMQ narrow; R(2) = 0.89 between Query 2 and SMQ Narrow+Broad. Generating automated groupings of terms for signal detection is feasible but requires additional efforts in modeling MedDRA terms in order to improve precision and recall of these groupings.

PMID: 23304363 [PubMed - in process]

HopX1 in Erwinia amylovora functions as an avirulence protein in apple and is regulated by HrpL.

Fri, 08/10/2012 - 05:45
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HopX1 in Erwinia amylovora functions as an avirulence protein in apple and is regulated by HrpL.

J Bacteriol. 2012 Feb;194(3):553-60

Authors: Bocsanczy AM, Schneider DJ, DeClerck GA, Cartinhour S, Beer SV

Abstract
Fire blight is a devastating disease of rosaceous plants caused by the Gram-negative bacterium Erwinia amylovora. This pathogen delivers virulence proteins into host cells utilizing the type III secretion system (T3SS). Expression of the T3SS and of translocated and secreted substrates is activated by the alternative sigma factor HrpL, which recognizes hrp box promoters upstream of regulated genes. A collection of hidden Markov model (HMM) profiles was used to identify putative hrp boxes in the genome sequence of Ea273, a highly virulent strain of E. amylovora. Among potential virulence factors preceded by putative hrp boxes, two genes previously known as Eop3 and Eop2 were characterized. The presence of functionally active hrp boxes upstream of these two genes was confirmed by β-glucuronidase (GUS) assays. Deletion mutants of the latter candidate genes, renamed hopX1(Ea) and hopAK1(Ea), respectively, did not differ in virulence from the wild-type strain when assayed in pear fruit and apple shoots. The hopX1(Ea) deletion mutant of Ea273, complemented with a plasmid overexpressing hopX1(E)(a), suppressed the development of the hypersensitivity response (HR) when inoculated into Nicotiana benthamiana; however, it contributed to HR in Nicotiana tabacum and significantly reduced the progress of disease in apple shoots, suggesting that HopX1(Ea) may act as an avirulence protein in apple shoots.

PMID: 22123252 [PubMed - indexed for MEDLINE]

Gramene database in 2010: updates and extensions.

Fri, 08/10/2012 - 05:45
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Gramene database in 2010: updates and extensions.

Nucleic Acids Res. 2011 Jan;39(Database issue):D1085-94

Authors: Youens-Clark K, Buckler E, Casstevens T, Chen C, Declerck G, Derwent P, Dharmawardhana P, Jaiswal P, Kersey P, Karthikeyan AS, Lu J, McCouch SR, Ren L, Spooner W, Stein JC, Thomason J, Wei S, Ware D

Abstract
Now in its 10th year, the Gramene database (http://www.gramene.org) has grown from its primary focus on rice, the first fully-sequenced grass genome, to become a resource for major model and crop plants including Arabidopsis, Brachypodium, maize, sorghum, poplar and grape in addition to several species of rice. Gramene began with the addition of an Ensembl genome browser and has expanded in the last decade to become a robust resource for plant genomics hosting a wide array of data sets including quantitative trait loci (QTL), metabolic pathways, genetic diversity, genes, proteins, germplasm, literature, ontologies and a fully-structured markers and sequences database integrated with genome browsers and maps from various published studies (genetic, physical, bin, etc.). In addition, Gramene now hosts a variety of web services including a Distributed Annotation Server (DAS), BLAST and a public MySQL database. Twice a year, Gramene releases a major build of the database and makes interim releases to correct errors or to make important updates to software and/or data.

PMID: 21076153 [PubMed - indexed for MEDLINE]

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