MOLGENIS and the eXtensible Genotype And Phenotype database project (xgap) Morris A. Swertz et al DAM & BOSC sigs Stockholm, June 27 2009 EBI Biobanking platform

Outline MOLGENIS database generator Free toolbox of automated best practices auot-generate useful data apps (sql,java,R,soap) from simple models As open platform that harmonizes data syntax, programming interfaces, user interaction, pluggable Demo eXtensible Genotype And Phenotype (xgap) To store various high-throughput genotype and phenotypes harmonized as platform for collaboration and analysis tools Current work

MOLGENIS database generator

Free toolbox of automated best practices auot-generate useful data apps (sql,java,R,soap) from simple models

As open platform that harmonizes data syntax, programming interfaces, user interaction, pluggable

Demo

eXtensible Genotype And Phenotype (xgap)

To store various high-throughput genotype and phenotypes harmonized

as platform for collaboration and analysis tools

Current work

MOLGENIS, why and how biologist biologist biological challenges inbreed 100 10.000 1,000,000 100,000 10,000 10 10,000,00 QTL profiles network correlate genome strains individuals markers expressions preprocess probes microarrays 100 hybridize 100,000 genotype genotypes norm exprs. map

MOLGENIS, why and how biologist biologist biological challenges suitable infrastructure inbreed 100 10.000 1,000,000 100,000 10,000 10 10,000,00 QTL profiles network correlate genome strains individuals markers expressions preprocess probes microarrays 100 hybridize 100,000 genotype genotypes norm exprs. map bioinformatician softw engineers €

MOLGENIS, why and how biologist biologist Reinventing wheels, Wasting time Hard to integrate biological challenges suitable infrastructure bioinformatician softw engineers inbreed 100 100.000 10,000,000 1000 10,000 10 1000 genotype individuals mass peaks genotypes QTL profiles strains network SNP arrays correlate LC/MS genome map preprocess aligned peaks €

Alternative strategy http://www.molgenis.org Swertz & Jansen (2007) Nature Reviews Genetics 8, 235-243 http://www.molgenis.org

MOLGENIS, why and how Platform and generators Little language <!-- entity organization --> <entity name= &quot;Experiment&quot; label= &quot;Experiment&quot; > <field name= &quot;ExperimentID&quot; key= &quot;1“ r eadonly= &quot;true&quot; label= &quot;ExperimentID(autonum)&quot;/> <field name= &quot;Medium&quot; type= &quot;xref&quot; xref_field= &quot;Medium.name&quot; /> /> <field name= &quot;Protocol&quot; label= &quot;Experiment Protocol&quot; /> <field name= &quot;Temperature&quot; type= &quot;int&quot; Blueprint model <!-- entity organization --> <entity name= &quot;Experiment&quot; label= &quot;Experiment&quot; > <field name= &quot;ExperimentID&quot; key= &quot;1“ r eadonly= &quot;true&quot; label= &quot; ExperimentID(autonum )&quot;/> <field name= &quot;Medium&quot; type= &quot;xref&quot; xref_field= &quot;Medium.name&quot; /> /> <field name= &quot;Protocol&quot; label= &quot;Experiment Protocol&quot; /> <field name= &quot;Temperature&quot; type= &quot;int&quot; + bioinformatician softw engineer inbreed 100 10.000 1,000,000 100,000 10,000 10 10,000,00 QTL profiles network correlate genome strains individuals markers expressions preprocess probes microarrays 100 hybridize 100,000 genotype genotypes norm exprs. 10.000 map biologist biologist http://www.molgenis.org Swertz & Jansen (2007) Nature Reviews Genetics 8, 235-243

Upgrade to new research Platform and generators Little language <!-- entity organization --> <entity name= &quot;Experiment&quot; label= &quot;Experiment&quot; > <field name= &quot;ExperimentID&quot; key= &quot;1“ r eadonly= &quot;true&quot; label= &quot;ExperimentID(autonum)&quot;/> <field name= &quot;Medium&quot; type= &quot;xref&quot; xref_field= &quot;Medium.name&quot; /> /> <field name= &quot;Protocol&quot; label= &quot;Experiment Protocol&quot; /> <field name= &quot;Temperature&quot; type= &quot;int&quot; Blueprint model <!-- entity organization --> <entity name= &quot;Experiment&quot; label= &quot;Experiment&quot; > <field name= &quot;ExperimentID&quot; key= &quot;1“ r eadonly= &quot;true&quot; label= &quot;ExperimentID(autonum)&quot;/> <field name= &quot;Medium&quot; type= &quot;xref&quot; xref_field= &quot;Medium.name&quot; /> /> <field name= &quot;Protocol&quot; label= &quot;Experiment Protocol&quot; /> <field name= &quot;Temperature&quot; type= &quot;int&quot; + bioinformatician softw engineer biologist biologist New Biology New Biology http://www.molgenis.org Swertz & Jansen (2007) Nature Reviews Genetics 8, 235-243 inbreed 100 100.000 10,000,000 1000 10,000 10 1000 genotype individuals mass peaks genotypes QTL profiles strains network SNP arrays correlate LC/MS genome map preprocess aligned peaks

Upgrade to new software tools Platform and software generators Little language <!-- entity organization --> <entity name= &quot;Experiment&quot; label= &quot;Experiment&quot; > <field name= &quot;ExperimentID&quot; key= &quot;1“ r eadonly= &quot;true&quot; label= &quot;ExperimentID(autonum)&quot;/> <field name= &quot;Medium&quot; type= &quot;xref&quot; xref_field= &quot;Medium.name&quot; /> /> <field name= &quot;Protocol&quot; label= &quot;Experiment Protocol&quot; /> <field name= &quot;Temperature&quot; type= &quot;int&quot; Blueprint model <!-- entity organization --> <entity name= &quot;Experiment&quot; label= &quot;Experiment&quot; > <field name= &quot;ExperimentID&quot; key= &quot;1“ r eadonly= &quot;true&quot; label= &quot;ExperimentID(autonum)&quot;/> <field name= &quot;Medium&quot; type= &quot;xref&quot; xref_field= &quot;Medium.name&quot; /> /> <field name= &quot;Protocol&quot; label= &quot;Experiment Protocol&quot; /> <field name= &quot;Temperature&quot; type= &quot;int&quot; + bioinformatician softw engineer biologist biologist inbreed 100 100.000 10,000,000 1000 10,000 10 1000 genotype individuals mass peaks genotypes QTL profiles strains network SNP arrays correlate LC/MS genome map preprocess aligned peaks http://www.molgenis.org Swertz & Jansen (2007) Nature Reviews Genetics 8, 235-243

Demo

Step 1: model* m.a.swertz@rug.nl / individuals expressions probes *Can also extract automatically from an existing database

m.a.swertz@rug.nl /

Step 2: generate Download and customize... Model file XML Generate APIs in Java, R, Web services and HTTP MyScript Plugins FormGen MenuGen TreeGen PluginGen MatrixGen JTypeGen JDBCMapGen JListGen JReadCsvGen HSQLGen JDatabaseGen MySQLGen    RMatrixGen WSGen RListGen data infrastructure user interaction infrastructure Communication infrastructure

Step 3: use result Lets see

Lets see

eXtensible Genotype And Phenotype database for QTL and GWAS experiments

Locus Specific database Clin. Trial metabase NextGen sequencing Proteo/Metabolomics Animal Observations Example projects

Locus Specific database

Clin. Trial metabase

NextGen sequencing

Proteo/Metabolomics

Animal Observations

XGAP - DAM Challenges Challenges: Share data between QTL collaborators Variety of species/methods Reuse the ad-hoc analysis protocols Aim: Simple common data model and format Common interaction layers (R, SOAP) Platform for reusable protocols/tools Reuse between individual projects inbreed 100 10.000 1,000,000 100,000 10,000 10 10,000,00 QTL profiles network correlate genome strains individuals markers expressions preprocess probes microarrays 100 hybridize 100,000 genotype genotypes norm exprs. 10.000 map Main work flow Data dependency Biomaterial/result Lab/analysis process Scale of information Associated data files process material 10,000

Challenges:

Share data between QTL collaborators

Variety of species/methods

Reuse the ad-hoc analysis protocols

Aim:

Simple common data model and format

Common interaction layers (R, SOAP)

Platform for reusable protocols/tools

Reuse between individual projects

First objective m.a.swertz@rug.nl / researcher researcher annotations Raw and processed data database my GaP

Genotype data 1. Data model M A R K E R S Subjects: STRAINS DATA ELEMENTS T r a i t s: TRAIT  SUBJECT Looking at standards and existing data sets Simple enough for everybody to create

Genotype data

1. Data model What about QTL data? / P R O B E S Traits: MARKERS T r a i t s:

What about QTL data?

1. Model / DATA (matrix) TRAIT SUBJECT DATA ELEMENT TRAIT  SUBJECT

1. Model / DATA ELEMENT TRAIT SUBJECT DATA ELEMENT Annotations: Individual, Strain, Sample, … Annotations Phenotype Probe Marker Mass Peak … Data: PhenotypeValues Raw QTLs other columns rows dimension ELEMENT

Annotations:

Individual,

Strain,

Sample,

…

Annotations

Phenotype

Probe

Marker

Mass Peak

…

Data:

PhenotypeValues

Raw

QTLs

other

Extensions for new experiments DATA ELEMENT TRAIT SUBJECT PROBE Name Gene Chromosme Locus MARKER Name Allele Chromosme Locus MASSPEAK Name MZ RetentionTime Panel Name Type: CSS, RIL.. Parent Panels INDIVIDUAL Name Strain Mother Father Sex SAMPLE Name Individual Tissue And so on … And so on … columns rows dimension ELEMENT

PROBE

Name

Gene

Chromosme

Locus

MARKER

Name

Allele

Chromosme

Locus

MASSPEAK

Name

MZ

RetentionTime

Panel

Name

Type: CSS, RIL..

Parent Panels

INDIVIDUAL

Name

Strain

Mother

Father

Sex

SAMPLE

Name

Individual

Tissue

Protocol graph from FuGE XGAP extends on standard FuGE (Jones ea, NatBiot 2007) / FuGE: Jones et al Nature Biotech 25, 1127-1133 DATA DATA Genotype data QTL data QTL Mapping Affy Array SNP Array DATA Expression data Mapping Protocol Illumina R Software Illumina Protocol Affy M430 Protocol Bead Studio DATA application Protocol Software Equipment Bioconductor Norm. Affy M430 platform DATA DATA DATA FuGE:

XGAP extends on standard FuGE (Jones ea, NatBiot 2007)

UML: XGAP extends FuGE m.a.swertz@rug.nl / Uniform core to ease sharing of data and tools Various traits for new research Various subjects for new research ? ?

2. Mode, run MOLGENIS

Connect to R statistics Workflow ready web-services UML documentation of your model Edit & trace your data Import/export to Excel plugin your own scripts (R/QTL) Tech keywords: object oriented data models, multi-platform java, tomcat/glassfish web server, mysql/postgresql database, Eclipse/Netbeans IDE, Java API, WSDL/SOAP API, R-project API, MVC, freemarker templates and css for custom layout, open source.

Proof of the pudding

Ongoing work

Next step: add processing Sheets thanks to Joeri van der Velde and Danny Arends Generalize for all MOLGENIS instances: (1) Extend MOLGENIS model for tool integration <tool name=“rqtl”> <input name=“data” entity=“data”/> … </tool> (2) Integrate workflow definition and execution Extending on Taverna/Galaxy model & APIs…

Next step: semantics The Pheno-OM project Integrating mouse and man Generalize for all MOLGENIS instances: Next: Add MOLGENIS components to integrate: (1) Ontology browsing Extending on BioPortal/OLS frameworks? (2) Semantic integration layer ???

The Pheno-OM project

Integrating mouse and man

Exploit standard generated interfaces Big distribute big data and tools Meta analysis Federation? Cloud computing?

Exploit standard generated interfaces

Big distribute big data and tools

Meta analysis

Acknowledgements Joeri van der Velde Joris Lops Tomasz Adamusiak Danny Arends Martijn Dijkstra Matthijs Kattenberg Tjeerd Abma Ate Boerema Henrikki Almusa Rudi Alberts Damian Smedley Katy Wolstencroft Andrew R. Jones Bruno M. Tesson Richard A. Scheltema Gonzalo Vera Rodriguez Rene Oostergo Helen E. Parkinson Ritsert C. Jansen Cisca Wijmenga Carole Goble Marco Roos M. Scott Marshall Paul Schofield John M. Hancock Juha Muilu Klaus Schughart Engbert O. de Brock Hans Hillege the LifeLines consortium the Trial Coordination Center the GEN2PHEN consortium the CASIMIR consortium the NBIC/BioAssist consortium

Joeri van der Velde

Joris Lops

Tomasz Adamusiak

Danny Arends

Martijn Dijkstra

Matthijs Kattenberg

Tjeerd Abma

Ate Boerema

Henrikki Almusa

Rudi Alberts

Damian Smedley

Katy Wolstencroft

Andrew R. Jones

Bruno M. Tesson

Richard A. Scheltema

Gonzalo Vera Rodriguez

Rene Oostergo

Helen E. Parkinson

Ritsert C. Jansen

Cisca Wijmenga

Carole Goble

Marco Roos

M. Scott Marshall

Paul Schofield

John M. Hancock

Juha Muilu

Klaus Schughart

Engbert O. de Brock

Hans Hillege

the LifeLines consortium

the Trial Coordination Center

the GEN2PHEN consortium

the CASIMIR consortium

the NBIC/BioAssist consortium

See us at the NBIC booth Add generator targets We have funding for several positions (PhD,SE) Read more: MOLGENIS for data integration: Smedley et al 2009, Brief. in Bioinformatics 9(6):532 Review of MOLGENIS type of systems (dated) Swertz & Jansen 2007, Nature Rev. Genetics 8(3):235 First MOLGENIS, in those times in PHP Swertz et al 2004, Bioinformatics 20(4)L2075 Questions http://www.molgenis.org http:// www.xgap.org

See us at the NBIC booth

Add generator targets

We have funding for

several positions (PhD,SE)

Read more:

MOLGENIS for data integration:

Smedley et al 2009, Brief. in Bioinformatics 9(6):532

Review of MOLGENIS type of systems (dated)

Swertz & Jansen 2007, Nature Rev. Genetics 8(3):235

First MOLGENIS, in those times in PHP

Swertz et al 2004, Bioinformatics 20(4)L2075