Source: IOWA STATE UNIVERSITY submitted to
DEVELOPMENT OF BIOINFORMATIC RESOURCES TO TRANSFER BIOLOGICAL INFORMATION ACROSS SPECIES
 
PROJECT DIRECTOR: Reecy, J. M.
 
PERFORMING ORGANIZATION
ANIMAL SCIENCE
IOWA STATE UNIVERSITY
AMES,IA 50011
 
NON TECHNICAL SUMMARY: One of the goals of the current USDA-NRICGP Animal Genome Bioinformatic RFA is to generate more integrative informatics tools to allow deeper mining of the vast amount of biological and genomic data being generated. With a reasonable effort, we envision the new VCMap as a powerful and flexible visual data exploration tool for integrating genomic maps and biological annotation across human, mouse, rat, dog, cow, pig, chicken, and sheep. It will allow a user to select what comparison they would like to visualize and then allow dynamic zoom, filter, and extended annotation features to mine deeper into the genomic and biological data associated with a region of interest across multiple species, to link to related genome browsers, and provide a means to download associated data in a report format. By utilizing a web service architecture, VCMap will change from a simple visualization tool to a dynamic visualization and annotation browser and will be a data provider in its own right. This way VCMap would become both a tool for the end user and a tool/resource for other bioinformaticians on which to build further tools, visualize and download annotations greatly increasing its impact. Furthermore, in order to insure efficient transfer of biological information between species, there is a huge need to develop an integrated trait ontology. In addition to the bioinformatics tools that will result from this proposal, the data that we will collect, curate, and make available to the public also has great value.
 
OBJECTIVES: Genetics has been revolutionized by genomic sequencing of multiple vertebrates, creating a new basis for comparative studies. Our long-range goal is to develop bioinformatic tools that will allow efficient transfer of comparative information from one species to another. The objectives of this application are to curate QTL data from livestock species, humans and model organisms, develop a comparative QTL viewer, and develop a trait ontology to link this information together. We plan to accomplish the overall objective of this application by pursuing the following research objectives: Objective 1: Build a new version of the online dynamic VCMapView tool with expanded capabilities. We expect to build an interactive comparative QTL viewer to transfer information between livestock and model organisms. Objective 2: Develop a trait ontology across species. We expect to develop a standardized trait ontology that can be used within and across species to facilitate efficient communication. Objective 3: Annotation of complex QTL and phenotype-associated genes across the included organisms. We expect that annotation of biology onto the genomes of multiple species will facilitate the identification of traits across species that may share a common mechanism or genetic pathway. Objective 4: Produce a stand-alone version of the VCMap environment. We anticipate that the VCMap environment will be of great use to investigators working with species other than mammals, e.g. lower eukaryotes or plants. The efficient transfer of comparative information between species is expected to have significant positive effects on the long-range improvement in and sustainability of United States agriculture.
 
APPROACH: Genetic research has been revolutionized by the mapping and sequencing of whole genomes: human, chicken, cattle, swine (on-going) and multiple other species (vertebrate and non-vertebrate). This achievement provides a powerful platform for comparative genomic studies in the evolution of species, gene identification across species as well as the mechanisms of gene function and disease. For many sequenced genomes, it is possible to query a public website to view sequence-based comparisons between organisms ranging from human to mouse, cow, chicken, or fugu. However, while most genome browsers and comparative genomics tools include conserved synteny and gene content information, there is a paucity of tools that also integrate mapped diseases or traits across species. VCMap will use map coordinates of genes, ESTs and STSs from various map sources (sequence, genetic, radiation hybrid) to generate comparative maps. The tool will incorporate curated, biological annotations of cattle, pigs, sheep, chicken, rat, mouse, and human traits, with an emphasis on Quantitative Trait Loci (QTL) for complex traits. This integrated visualization will provide a unique link between not only the genomes but also the biology across these species. This tool will allow users to easily and efficiently transfer genomic and biological data across species. Upon reading QTL literature, it becomes evident very quickly that researchers do not use an agreed upon trait nomenclature. For example, one manuscript may use the term backfat, while another uses ribfat. Upon closer examination of the manuscripts it becomes evident that the manuscripts are describing the exact same trait. While there are several biological ontologies that have been developed (e.g. Gene Ontology), there is currently no completed ontology that deals with traits that are specific to farm animals. We have begun to develop a livestock phenotype ontology (http://www.animalgenome.org/bioinfo/projects/ATO/), but it is only in very early stages of development. The mammalian phenotype ontology that is currently available was designed for mouse phenotypes and is restricted to abnormal phenotypes most likely to be seen in knockout mice. Most livestock phenotypes are not present in the ontology and the ontology is not designed for the specific quantitative traits measured in QTL studies. Furthermore, there is no phenotype ontology that has integrated QTL marker data with phenotypic trait information for farm animals. If such an ontology were available, genomic and biological information could be linked across species.
 
CRIS NUMBER: 0212867 SUBFILE: CRIS
PROJECT NUMBER: IOW05157 SPONSOR AGENCY: NIFA
PROJECT TYPE: NRI COMPETITIVE GRANT PROJECT STATUS: EXTENDED MULTI-STATE PROJECT NUMBER: (N/A)
START DATE: Apr 1, 2008 TERMINATION DATE: Mar 31, 2012

GRANT PROGRAM: IDENTIFYING GENETIC MECHANISMS & GENE MAPPING
GRANT PROGRAM AREA: Animal Systems

CLASSIFICATION
Knowledge Area (KA)Subject (S)Science (F)Objective (G)Percent
303391010802.250%
304391010802.250%

CLASSIFICATION HEADINGS
KA303 - Genetic Improvement of Animals
KA304 - Animal Genome
S3910 - Cross-commodity research--multiple animal species
F1080 - Genetics
G2.2 - Increase Efficiency of Production and Marketing Systems


RESEARCH EFFORT CATEGORIES
BASIC 100%
APPLIED (N/A)%
DEVELOPMENTAL (N/A)%

KEYWORDS: bioinformatics; database; quantitative trait loci; curation; ontology

PROGRESS: Apr 1, 2010 TO Mar 31, 2011
OUTPUTS: Trait Ontology Development: A Vertebrate Trait Ontology Consortium consisting of the AnimalQTLdb, Rat Genome Database and Mouse Genome Informatics has been working on the Vertebrate Trait Ontology. Progress for the ontology development included: 1) incorporation of muscle, adipose, and nutrition traits in collaboration with INRA; 2) removal of livestock product traits and establishment of a separate ontology; 3) assessment of term names and modification to ensure that they represent traits and not measurements; and 4) creation of a list of commonly used terms and continuing development of their definitions, to improve consistency throughout the ontology. QTL Curation: 175 rat, 50 human, 2,323 cattle, 723 pig, 588 chicken, and 264 sheep QTLs have been curated this past year. Animal QTLdb now has 6,344 swine, 4,682 cattle, 2,451 chicken, and 348 sheep QTL, respectively. The QTLdatabase was accessed 554,491 times by 8,048 unique users in 2010 (Jan-Dec). Improvement of the Comparative QTL Viewer: Since the release of the VCMap tool, further improvements have been completed and incorporated into a 2.0 release of the tool. This update made the system much more user friendly and intuitive, expanding the versatility and utility of the tool. VCMap version 2.0 has made significant improvements to the user interface and supported features of the software tool. Usability of the user interface has been improved, especially with respect to the navigation of large-scale regions on the order of multiple megabases. Most importantly, the tool now supports the ability to load custom datasets from text files in a variety of common formats including GFF3, BED, and SAM/BAM. This feature greatly increases the utility of the tool because it now provides users with the ability to perform comparative research using their own personal, private research data with VCMap as a framework for navigating and investigating their data. The ability to export publication quality images of the data visualization was added. Some genomic map data and annotation from Ensembl was incorporated into the VCMap database, and improvements were made to the load script to enable more frequent updating of the existing data. The VCMap website has been visited 363 times since December 1st of 2010, by 238 unique visitors. After launching the tool from the website once, users can launch the tool directly using Java WebStart technology, therefore the number of users of the tool may in fact exceed the number of visitors to the website. Future improvements: In order to handle high-throughput sequencing datasets without compromising usability of the software, improvements must be made to the underlying rendering and visualization aspects of VCMap. Additionally, we plan to expand the available Radiation-Hybrid map data, as these maps can be very useful as an intermediate map to compare two different species for which comparative data may not exist. We also plan to add more annotation to the system, including possible inclusion of dbSNP data or other sources of common SNPs. We also plan to expand the Ensembl data currently loaded into the system, including more comparative data from Ensembl. PARTICIPANTS: James Reecy, Zhiliang Hu, Cari Park (Iowa State University, Ames, IA); Mary Shimoyama, Mindy Dwinell, Diane Munzenmaier (Rat Genome Database, Milwaukee, WI); Anne Kwitek (University of Iowa, Iowa City, IA); Steve Davis (Bio::Neos, Iowa City, IA). TARGET AUDIENCES: This research is targeted toward helping molecular/quantitative geneticists throughout the world. PROJECT MODIFICATIONS: The only major change in the current project is the way the work is being accomplished. Originally, it was proposed that all programming for the development of the comparative QTL viewer would be accomplished at Iowa State University. However, we quickly realized that it would be more cost effective to outsource the programming to Bio::Neos Inc.

IMPACT: 2010-04-01 TO 2011-03-31 Now that we have the second version of the new tool, we have the platform established for multiple annotations and the addition of new species. An immediate goal in the next version is to update the conserved synteny information. Currently, the UCSC data does not provide all pairwise cross-species alignments for the species in VCMap. Therefore, we will incorporate additional source data sets from Ensembl to provide additional data and options for users. We are also looking into incorporating additional annotations such as SNPs, CNVs, and expression data. This flexible platform allows visualization and downloading of comparative data and will provide a means for users to upload their own data for visualization on the VCMap platform. The incorporation of livestock and rat traits with those included in the Mammalian Phenotype Ontology will allow for the standardization of nomenclature and facilitate comparisons across species.

PUBLICATION INFORMATION: 2010-04-01 TO 2011-03-31
Zhi-Liang Hu, Carissa A. Park, Eric R. Fritz and James M. Reecy (2010). QTLdb: A Comprehensive Database Tool Building Bridges between Genotypes and Phenotypes. Invited Lecture with full paper published electronically on The 9th World Congress on Genetics Applied to Livestock Production. Leipzig, Germany August 1-6, 2010.

PROJECT CONTACT INFORMATION
NAME: Good, C.
PHONE: 515-294-4544
FAX: (N/A)