Embed Size (px)
DESCRIPTION
Quest for Orthologs (QfO) is a volunteer effort to jointly create a firmer foundation for comparative biology research. Extrapolating knowledge from a handful of organisms for which experimental data is available to other living organisms is the heart of comparative biology, and orthology assignments are axiomatic. Whether the aim is to find the gene in a model organism corresponding to a human disease gene, inferring the function of a newly sequenced gene using available experimental assays from its orthologs, or inferring species phylogenies by tracing the evolution of orthologous groups, reliable ortholog predictions are needed. Any improvement to this essential base will offer enormous benefit to the entire biological community. Currently more than 30 different phylogenomic databases provide their ortholog analysis results to the scientific community, each differing in many ways—number of species, taxonomic range, sampling density, applied methodology, and more. In addition, phylogenomic databases differ in their concepts, making direct benchmarking problematic and presenting major obstacles to the user community looking for relationships between genes. One of the prerequisite for the QfO consortium is a shared species phylogeny, which is used for the final determination of gene relationships during construction of sequence-based gene trees. A cladogram was therefore constructed for the 147 species of the reference proteomes (http://www.ebi.ac.uk/reference_proteomes/) based on information from various resources (http://wiki.isb-sib.ch/swisstree/Species_tree_for_Quest_for_Orthologs_reference_proteomes_2013). This talk presents the current progress by the QfO consortium and ideally will lead to a discussion of common needs and open questions.
Citation preview
Quest for Orthologs*anchoring comparative biology researchSharing and delivery of reusable phylogenetic knowledgeTDWG 2013 Annual Conference - October 2013 Florence, Italy
*http://questfororthologs.org/
Wednesday, October 23, 13
Evolutionary conservation allows knowledge transfer between well-characterized model organisms to human & other organisms and is the basis for comparative genomic studies
Wednesday, October 23, 13
The barriersMore than 30 phylogenomic databases provide their analysis results to the scientific community.
The content of these databases differ
The concepts of these databases also differ
Complex/slow pipelines
Unavailability as stand alone programsDifferent output formatsLack of benchmarking data sets
Consequently comparing and choosing is difficult
Wednesday, October 23, 13
Who we are
SWISS INSTITUTE OF BIOINFORMATICS
EUROPEAN BIOINFORMATICS INSTITUTE
STOCKHOLMS UNIVERSITET
UNIVERSITY OF LAUSANNE
JACKSON LABORATORY
EIDGENÖSSISCHE TECHNISCHE HOCHSCHULE ZÜRICH
INSTITUT DE GÉNÉTIQUE ET MICROBIOLOGIE
UNIVERSITÉ DE GENEVE
NATIONAL INSTITUTE FOR BASIC BIOLOGY, JAPAN
EUROPEAN MOLECULAR BIOLOGY LABORATORY
INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE
UNIVERSITÄT BONN
UNIVERSIDAD DE MURCIA
CENTRE INTERNATIONALE POUR LA RECHERCHE AGRONOMIQUE POUR LE DÉVELOPPEMENT
JOINT GENOME INSTITUTE SYNGENTA
UNIVERSITY OF CAMBRIDGE
UNIVERSITÉ DE LYON CENTRE DE REGULACIÓ GENOMICS, BARCELONA
PRINCETON UNIVERSITY UNIVERSITY OF PENNSYLVANIA
SANGER INSTITUTE
Wednesday, October 23, 13
Quest for Orthologs’ objectivesA collaboration of phylogenomic databases
Use shared reference datasets (proteomes and species trees)
Benchmark orthology predictions
Use an agreed format
Evaluate emerging new methods
Wednesday, October 23, 13
QfO - proteomesCriteria 1: include the major experimental model organisms
Criteria 2: include a broad taxonomic range of genomes
Common dataset: QfO Reference Proteome: http://www.ebi.ac.uk/reference_proteomes
Currently 147 species that are publicly available and are generated using UniProtKB, Ensembl and Ensembl Genomes.
Additional species on request, annual release in April
Wednesday, October 23, 13
QfO - Format
Common format: OrthoXML: http://seqxml.org
Designed for representing the orthology relationships that are generated as output
Sign ups: Ensembl Compara*, HCOP, InParanoid*, MBGD Microbial Genome Database, OMA*, OrthoInspector, OrthoMCL, Panther, PHOG, PhyloFacts, PhylomeDB, ProGMap, Roundup*
Wednesday, October 23, 13
QfO - BenchmarkCompared: Ensembl Compara, InParanoid (Full, core), MetaPhOrs (Missing 3 genomes), OMA (Pairs, Groups, HOGs), Orthoinspector 1.30, PANTHER 8.0 (LDO only, all), PhylomeDB, RSD 0.8 1e-5 (RoundUp)OrthoBench: http://orthology.benchmarkservice.orgBattery of approaches: Species-tree discordance test: Gold standard gene trees: Gold standard (hierarchical) orthologous groupsMinimum standard and sanity check (already useful): Minimum Information for an Orthology Prediction Algorithm?Guide to improve algorithms
Wednesday, October 23, 13
A species tree is keyA reliable species phylogeny enhances prediction of gene relationships
Current cladogram comprised of 147 species from the reference datasets and is based on information from various resources
Newick format3 identifiers: UniProtKB species code, scientific name, NCBI taxidRelevant publications for speciation nodes possible
For QfO benchmarking only needs to cover current accepted models of species evolution
A time-tree would be desirable to define rules for the introduction of multi-furcating nodes for benchmarking purposes
Ortholog DB providers use it for gene/species tree reconciliation
Wednesday, October 23, 13
Ontology based annotation of trees
Wednesday, October 23, 13
ResourcesQuest for Orthologs—http://questfororthologs.org/
Alan Wilter Sousa da Silva— http://www.ebi.ac.uk/reference_proteomes
Eric Sonnhammer & Matthieu Muffato— http://seqxml.org
Adrian Altenhoff & Christophe Dessimov— http://orthology.benchmarkservice.org
Brigitte Boeckman—wiki.isb-sib.ch/swisstree
Wednesday, October 23, 13
Our questionsAre model differences among the different ToLs documented and if yes, is this info made public or can be made available to QfO?Which tree format is best to use for data comparison and update?Are confidence values for internal nodes in the ToLs made available?Are ToLs available for download (formats, update frequencies, release identifiers?,...)Are species identifiers of ToL projects in sync with the NCBI TaxIds? Is there a point of contact and communication? How can we productively engage with the ToL & taxonomy community on a cooperative effort?
Wednesday, October 23, 13
SWISS INSTITUTE OF BIOINFORMATICSBrigitte BoeckmannUNIVERSITÉ DE LYONVincent DaubinEUROPEAN MOLECULAR BIOLOGY LABORATORYKristoffer ForslundCENTRE DE REGULACIÓ GENOMICS, BARCELONA Toni GabaldonEUROPEAN BIOINFORMATICS INSTITUTEMatthieu Muffato
Fabian Schreiber SANGER INSTITUTE
Special thanks to
Wednesday, October 23, 13
