The GMOD Project Lincoln Stein Cold Spring Harbor Laboratory

Test Subject: Michael Caudy oDrosophila neurobiologist oProneural differentiation onotch pathway oHLH transcriptional activators/repressors oachaete/scute complex oNo computer science training oTook my “bioinformatics for biologists” course

“Simple” Problem oDiscover the transcriptional factor binding site code controlling proneural differentiation.

Regular Expression Search oUsing achaete promoter as exemplar, search for combinations of known binding sites in particular architectures

Mike’s Got Lots of Data o90-11,000 TF binding site clusters o100s-1000s of genes omillions of interactions oWhich genes are involved in neural differentiation? oWhich have interactions with the pathway? oWhich have suggestive mutant phenotypes?

Mike Needs a Database oDatabase management system for proneural differentiation genes. oVisualization/exploration tools for relationship of genes to putative TF clusters. oLiterature citations oLink out to FlyBase, Genbank & other DBs. oAdd notes and other annotations.

Try to do it with Filemaker o“Cluster-centric” vs “gene-centric”? oData import from FlyBase? oStoring images? oMaintaining relationships between genes & clusters? oUpdates?

Mike Needs a MOD oModel Organism Database oRepository for reagents oStocks, vectors, clones oGenetic & physical maps oLarge-scale data sets oGenome oEST sets, microarray results, 2-cell hybrid interactions oLiterature oOntologies & Nomenclature oMeetings, announcements

Example MOD: WormBase

Looking for Sex

An Author Entry

Bibliography

Citation

Gene

Genome

Proteome

Comparative Genomics

Functional Genomics

Anatomy

How WormBase Works ACeDB Images, Movies Database access library Web server Perl scripts You MySQL Genomic Data

Can Mike reuse WormBase to manage his data? No!

Sorry Mike oWormBase website difficult to install oData model nematode-centric oData entry tools very process- specific oCustomization difficult oSoftware documentation uneven oStandard operating procedure documentation uneven

MOD Redux oSGD, MGD, FlyBase, TAIR, RGD… oThe same basic idea as WormBase oImplementation entirely different oWheel reinvented many times oLittle software sharing oThis madness must stop!

The GMOD Project oPortable, open source software to support model organism databases oMultiple MODs involved oWorm, fly, yeast, mouse, arabidopsis, rat, monocot, [fugu], [E. coli] oFunded by NIH as of June 2002 oProgrammers, coordinator, quarterly meetings

GMOD Home Page

The GMOD Pyramid Open Source DBMS & Middleware Modular Schema Modular Applications

A MOD Construction Set genome genetic maps liter- ature genomes Middleware Layer Database Layer Appplication Layer mapscitations genome browser genome editor map browser map editor citation browser citation editor Bioperl BioJava BioPython annotation pipeline

Chado – Modular Schema oCommon schema for use by FlyBase and WormBase oOntology Driven oSmall number of generic tables e.g. “feature” oControlled vocabulary names object types and relationships among them: o“achaete protein is a HLH activator” o“m8 protein inhibits achaete transcription” oEvidence-Savvy

GMOD Applications oApollo genome annotation editor oGbrowse generic genome browser oPubSearch literature curation editor oCMAP comparative map browser oIMD insertional mutagenesis database management system

Apollo – BDGP & Sanger Center

Apollo Data adapters oParser -> data models -> display oExisting data adapters oGAME XML oGFF oEnsembl CGI server oDAS oWrite your own data adapter! oExtend AbstractDataAdapter class oDisplay options defined in config file

Who is Using Apollo? oBDGP oReannotated Drosophila genome oBristol-Myers Squibb oLaunching Apollo from web browser via mime types oGNF oJDBC adapter layer over BioSQL oBiogen oView human genome alignment between public and Biogen internal database oConnected BLAT pipeline to Apollo oHGMP-RC Fugu Genomics group oDisplaying annotations on fugu scaffolds

PubSearch – TAIR & RatDB

PubSearch – Gene Association

IMD – Insertional Mutagenesis Db

CMap – Gramene

Cmap – Detailed View

GBrowse – WormBase

GBrowse – Zoomed in

GBrowse – Zoomed Way In

GBrowse – Zoomed Way Way In

GBrowse – Keyword Search

GBrowse – Third Party Annotations

Sequence dumps & other reports

Extensively Customizable oEnd-user oTurn tracks on and off, change order, change packing & labeling attributes (stored in cookie) oData provider oChange fonts, colors, text. oChange overview – genetic map, contigs, coverage, karyotype. oDefine new tracks using simple config file. oTinker with track appearance to hearts content.

Adding a New Track (a) Create a GFF file named “deletions.gff” Chr1 targeted deletion Deletion d101k2 Chr1 targeted deletion Deletion d680k2 Chr2 targeted deletion Deletion d007k2 (b) Run the load_gff.pl script > load_gff.pl –d example_database deletions.gff Loading features… Done. 3 features loaded. (c) Add a new track “stanza” to the gbrowse configuration file [Knockout] feature = deletion glyph = span fgcolor = red key = Knockouts link = citation = These are deletion knockouts produced by the example knockout consortium (

Extensively Extensible Apache Web Server gbrowse CGI script BioPerl library Bio::DB::GFF adaptor Chado adaptor MySQL/Postgres Plugins Bio::Graphics library Oracle Oracle adaptorFlat File adaptor Flat Files Glyphs

GBrowse on GenBank? Apache Web Server gbrowse CGI script BioPerl library Plugins Bio::Graphics library Glyphs GenBank Proxy Adaptor GenBank GBrowse on GenBank! Bio::DB::GFF adaptor MySQL

B. burgdorferi via GenBank proxy

Who is Using GBrowse? oGMOD Members oWormBase, FlyBase, RatDB oHGMP-RC Fugu genomics group oKEGG (multiple microorganisms) oIngenium AG (mouse) oBristoll-Myers Squibb (drosophila) oTexas A&M University (salmonella) oMcGill University (human chr7) oInstitute of Systems Biology (human)

Genome Knowledgebase (GK)

“Constellation View” (in dev) TCA Cycle Oxidative Decarboxylation Amino Acid Biosynthesis Ethanol Catabolism Glucose Metabolism RNA Splicing DNA Replication

“Constellation View” (in dev) TCA Cycle Oxidative Decarboxylation Amino Acid Biosynthesis Ethanol Catabolism Glucose Metabolism RNA Splicing DNA Replication

Can Mike use GMOD to manage his data? Almost

Mike’s very own flybase

Uploaded Annotations

Details

Essential Pieces in Progress oGeneric MOD web site oStrain & phenotype curation tools oPathway tools and browsers oTree (e.g. phylogenetic) tools & browsers oBiopipe – genome annotation pipeline

Find out more about GMOD oGo to oExamine software matrix oFind a project you’re interested in oContact project leader oOr contact Scott Cain: oOr mail

Credits CSHL Adrian Arva Shuly Avraham Scott Cain Ken Clark Allen Day Xiaokang Pan BDGP Nomi Harris Suzanna Lewis Chris Mungall John Richter ShengQiang Shu Colin Weil EBI Michele Clamp Stephen Searle Carnegie Institute Sue Rhee Danny Yoo Harvard David Emmert Stan Letovsky Cornell Medical School Michael Caudy