Databases to Support Disease-Focused Research Type 1 Diabetes Huntington’s Disease

Databases to SupportDatabases to SupportDisease-Focused ResearchDisease-Focused Research

Type 1 DiabetesType 1 DiabetesHuntington’s DiseaseHuntington’s Disease

Nat GoodmanNat GoodmanInstitute for Systems BiologyInstitute for Systems Biology

January 2003January 2003

Slide 2VanBUG January, 2003Nat Goodman

The Basic IdeaThe Basic Idea

Database (website) to support research of Database (website) to support research of scientists working on diseases of interestscientists working on diseases of interest

Key challenge: make it useful!Key challenge: make it useful! Data must beData must be

relevantrelevant to current research to current research rigorously rigorously accurateaccurate timelytimely coordinatedcoordinated with other databases with other databases

Steering committee provides scientific directionSteering committee provides scientific direction Also, easy-to-use, Also, easy-to-use, yaddayadda, , yaddayadda, , yaddayadda

Slide 3VanBUG January, 2003Nat Goodman

What Else is Like This?What Else is Like This? Other disease-focused websitesOther disease-focused websites

Alzheimer Research Forum (Alzforum) Alzheimer Research Forum (Alzforum) http://www.alzforum.orghttp://www.alzforum.org ? ALS Therapy Development Foundation (ALS-TDF)ALS Therapy Development Foundation (ALS-TDF) Technology Technology disease databases disease databases

– Stanford breast cancer microarray websiteStanford breast cancer microarray website Any others?Any others?

Model organism databases Model organism databases MGD, FlyBase, WormBase, TAIR, SGD, …MGD, FlyBase, WormBase, TAIR, SGD, …

Protein family databasesProtein family databases GPCRs, cytochrome P450s, …GPCRs, cytochrome P450s, …

Locus-specific databases Locus-specific databases HLA, CF, …HLA, CF, …

Alliance for Cellular Signaling (AfCS)-Nature Gateway Alliance for Cellular Signaling (AfCS)-Nature Gateway

Slide 4VanBUG January, 2003Nat Goodman

Potential Data ScopePotential Data Scope Genomic regionsGenomic regions Genes & proteinsGenes & proteins

functional summariesfunctional summaries curated sequences, genomic curated sequences, genomic

context, structurescontext, structures orthologs, families, multiple orthologs, families, multiple

alignmentsalignments Microarray resultsMicroarray results GenotypesGenotypes Protein-protein interactionsProtein-protein interactions Pathway modelsPathway models Empirical results on hot topicsEmpirical results on hot topics ReagentsReagents

antibodies, mouse models, antibodies, mouse models, clones, constructs, …clones, constructs, …

Therapeutic studiesTherapeutic studies drug, transplantation, gene drug, transplantation, gene

transfertransfer molecular, cellular, lower molecular, cellular, lower

organism, mouse, other organism, mouse, other mammalsmammals

clinicalclinical Patient informationPatient information

clinical & pathologic featuresclinical & pathologic features BiomarkersBiomarkers Literature scanning and Literature scanning and

alertingalerting Reports of negative and “ho-Reports of negative and “ho-

hum” resultshum” results Lay explanationsLay explanations

Slide 5VanBUG January, 2003Nat Goodman

Practical ConcernsPractical Concerns

Too much dataprioritize!

Steering committee to the rescue

Too much overlapcollaborate!

AlzforumAlzforumRefSeqRefSeq

GOGOStanford HOPES!!!Stanford HOPES!!!

OMIMOMIMBINDBIND

?? MGD MGD MEDLINEMEDLINE

Too much softwarereuse!AlzforumAlzforum

other collaborating databases other collaborating databases PubCrawler PubCrawler

GBrowseGBrowseBioPerl BioPerl

Generic Model Organism Generic Model Organism Database (GMOD)Database (GMOD)

Slide 6VanBUG January, 2003Nat Goodman

Some Differences Between ProjectsSome Differences Between Projects

Data TypeData Type Type 1 DiabetesType 1 Diabetes HDHD

GenomicsGenomics ~17 susceptibility ~17 susceptibility regionsregions Single gene disorderSingle gene disorder

GenesGenes Several hundred genes Several hundred genes in susceptibility regionsin susceptibility regions

~40 huntingtin (Htt) interactors~40 huntingtin (Htt) interactors~100 genes of interest~100 genes of interest

MicroarrayMicroarray A few datasets availableA few datasets availableHereditary Disease Array Hereditary Disease Array Group led by Jim OlsonGroup led by Jim Olson

Others ?Others ?

GenotypingGenotyping Consortium for fine-Consortium for fine-scale mappingscale mapping

Two efforts to map age-of-Two efforts to map age-of-onset modifiersonset modifiers

TherapiesTherapies

Coordinated program for Coordinated program for islet cell transplantationislet cell transplantationGene & drug therapyGene & drug therapy

Pharma, too!Pharma, too!

Semi-coordinated program for Semi-coordinated program for drug screeningdrug screening

Separate clinical studiesSeparate clinical studiesOrphan diseaseOrphan disease

Slide 7VanBUG January, 2003Nat Goodman

First Data Scope for HD WebsiteFirst Data Scope for HD Website

Data TypeData Type DetailsDetails

Large scale Large scale datasetsdatasets

Mouse & molecular drug screeningMouse & molecular drug screeningProtein-protein interactions (Hughes, Myriad ProteomicsProtein-protein interactions (Hughes, Myriad Proteomics))Protein abundance in cerebrospinal fluid (Watts, ISB)Protein abundance in cerebrospinal fluid (Watts, ISB)

Gene listGene listHuman, mouse, rat orthologsHuman, mouse, rat orthologsSequencesSequencesFunctional summariesFunctional summaries

Empirical Empirical results results

Example: Htt interaction with transcription factors - Example: Htt interaction with transcription factors - binding, transcriptional activity, cell deathbinding, transcriptional activity, cell death

ReagentsReagentsAntibodiesAntibodiesGenetic constructsGenetic constructs

Pathway Pathway modelsmodels

Hypothesized disease mechanismsHypothesized disease mechanismsExample: Example: Htt & CREB-mediated transcription Htt & CREB-mediated transcription

Slide 8VanBUG January, 2003Nat Goodman

Pathway Model (Wild type)Pathway Model (Wild type)Normal CREB-mediated transcription

Software: VisualCell™ from Gene Network

Sciences

Slide 9VanBUG January, 2003Nat Goodman

Pathway Model (Diseased)Pathway Model (Diseased)

Software: VisualCell™ from Gene Network Sciences

Slide 10VanBUG January, 2003Nat Goodman

Steering Committee ResponseSteering Committee Response

Slide 11VanBUG January, 2003Nat Goodman

Steering Committee GuidelinesSteering Committee Guidelines

Peer-review! Peer-review!

Connect everything to literatureConnect everything to literature

Rigorously scrutinized, but diverse, scienceRigorously scrutinized, but diverse, science

Data – “just the facts, Ma’am” – not conjectureData – “just the facts, Ma’am” – not conjecture

Hypotheses presented as such – not as factHypotheses presented as such – not as fact

Slide 12VanBUG January, 2003Nat Goodman

My Response My Response Hmm… this is

kinda narrow for a community

website

Slide 13VanBUG January, 2003Nat Goodman

CompromiseCompromise

Community information

Non-reviewed

Primarydatasets

Non-reviewed

CoreReviewed scientific

materialTied to literature

Steering committee in charge!

Slide 14VanBUG January, 2003Nat Goodman

Current Core Data ScopeCurrent Core Data ScopeData TypeData Type DetailsDetails

Comprehensive bibliography Comprehensive bibliography Milestone papersMilestone papers

Annotation by curators & committeeAnnotation by curators & committeeUser commentsUser comments

Published drug screens in mousePublished drug screens in mouse Bibliography & datasetBibliography & dataset

Mouse modelsMouse models Bibliography & datasetBibliography & dataset

AntibodiesAntibodies Bibliography & datasetBibliography & dataset

Published microarray studiesPublished microarray studies Bibliography, lists of changed Bibliography, lists of changed genes, links to full datasetsgenes, links to full datasets

Gene listGene list

BibliographyBibliographyHuman, mouse, rat orthologsHuman, mouse, rat orthologsSequencesSequencesHtt interactionsHtt interactionsShort functional descriptionsShort functional descriptions

Slide 15VanBUG January, 2003Nat Goodman

Current Core ServicesCurrent Core Services

Genome / gene browserGenome / gene browser View genes in human, mouse, rat syntenic regionsView genes in human, mouse, rat syntenic regions Accesses UC Santa Cruz DAS server plus local databasesAccesses UC Santa Cruz DAS server plus local databases All standard Santa Cruz information visible here, tooAll standard Santa Cruz information visible here, too Based on GBrowse – collaboration with L. SteinBased on GBrowse – collaboration with L. Stein

Literature alertingLiterature alerting Specify MEDLINE queriesSpecify MEDLINE queries Can include our bibliographiesCan include our bibliographies System runs periodically to get new hitsSystem runs periodically to get new hits Based on PubCrawler– collaboration with K. Wolfe, K. Based on PubCrawler– collaboration with K. Wolfe, K.

HokampHokamp

Slide 16VanBUG January, 2003Nat Goodman

Current Satellite Data ScopeCurrent Satellite Data ScopeData TypeData Type DetailsDetails

NewsNews Like news in Like news in ScienceScience and and NatureNature

ForumForum

Interviews with leading scientistsInterviews with leading scientistsLive discussions on hot topics with Live discussions on hot topics with subsequent transcriptssubsequent transcriptsWeb delivery of presentations Web delivery of presentations Mini-reviews derived from aboveMini-reviews derived from above

Calendar of eventsCalendar of events Conferences, etc.Conferences, etc.

Contact info for HD researchersContact info for HD researchers With permission!With permission!

Lay explanationsLay explanations For major sections, at leastFor major sections, at least

Primary datasetsPrimary datasetsProtein-protein interactions (HughesProtein-protein interactions (Hughes))Protein abundance in CSF (Watts)Protein abundance in CSF (Watts)

Slide 17VanBUG January, 2003Nat Goodman

Help From Our FriendsHelp From Our FriendsData TypeData Type WhoWho WhatWhat

All bibliographiesAll bibliographies AlzforumAlzforum citation databasecitation database

Comprehensive bibliographyComprehensive bibliography AlzforumAlzforum scanning & librarianscanning & librarian

Mouse modelsMouse models AlzforumAlzforum databasedatabase

AntibodiesAntibodies AlzforumAlzforum database & curatordatabase & curator

Published microarray studiesPublished microarray studies HDAGHDAG data & reviewdata & review

Gene listGene list

MGDMGD orthologs (we hope)orthologs (we hope)

RefSeqRefSeq sequences, descriptionssequences, descriptions

GOGO annotationsannotations

BINDBIND Htt interactionsHtt interactions

News, forum, calendar, contactsNews, forum, calendar, contacts AlzforumAlzforum

Lay explanationsLay explanations HOPESHOPES

Primary datasetsPrimary datasets Myriad, ISBMyriad, ISB datadata

Slide 18VanBUG January, 2003Nat Goodman

Software ArchitectureSoftware Architecture

Perl / CGI

scripts

RefSeq

MGD (?)

BIND

local databases

citations

antibodies

mouse models

news & things

Alz

foru

m

Other friends

Delivery by FTP & API, too

web delivery

Slide 19VanBUG January, 2003Nat Goodman

Genome Browser ScreenshotGenome Browser Screenshot

Slide 20VanBUG January, 2003Nat Goodman

Alzforum Home PageAlzforum Home Page

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Alzforum Papers of the WeekAlzforum Papers of the Week

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Alzforum Mouse Model ListAlzforum Mouse Model List

Slide 23VanBUG January, 2003Nat Goodman

A Few Words About IPA Few Words About IP

Open sourceOpen source Open dataOpen data Strong privacyStrong privacy

Slide 24VanBUG January, 2003Nat Goodman

Four Rules for a Successful WebsiteFour Rules for a Successful Website1.1. Too much dataToo much data

Prioritize!Prioritize! What will be most useful?What will be most useful? Rely on scientific expertsRely on scientific experts

2.2. Too much softwareToo much software Reuse!Reuse! Lots of great software availableLots of great software available Developers willing to helpDevelopers willing to help

3.3. Too much overlapToo much overlap Collaborate!Collaborate! Many databases welcome thisMany databases welcome this Less work – better product -- more fun!Less work – better product -- more fun!

4.4. Obsess on qualityObsess on quality Bad data wastes everyone’s timeBad data wastes everyone’s time

Slide 25VanBUG January, 2003Nat Goodman

AcknowledgementsAcknowledgements

ISB Project TeamISB Project TeamGeorge LakeGeorge Lake

Michelle WhitingMichelle WhitingPaul EdlefsenPaul EdlefsenRobert HubleyRobert Hubley

HDFHDFCarl JohnsonCarl Johnson

Minka van BeuzekomMinka van Beuzekom

Steering CommitteeSteering CommitteeCarl Johnson and Minka Carl Johnson and Minka

van Beuzekom, HDFvan Beuzekom, HDF

Dan GoldowitzDan GoldowitzUniversity of University of TennesseeTennessee

Emma HocklyEmma HocklyGuy’s HospitalGuy’s Hospital

Bruce KristalBruce KristalCornell UniversityCornell University

Marcy MacDonaldMarcy MacDonaldMassachusetts Massachusetts

General HospitalGeneral Hospital

Ray TruantRay TruantMcMaster UniversityMcMaster University

AlzforumAlzforumJune KinoshitaJune Kinoshita

RefSeqRefSeqKim PruittKim Pruitt

GO ConsortiumGO ConsortiumEvelyn CamonEvelyn Camon

HOPESHOPESBill DurhamBill Durham

HDAGHDAGJim OlsonJim Olson

Myriad ProteomicsMyriad ProteomicsBob HughesBob Hughes

ISBISBJulian WattsJulian Watts