>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

GS2PATH:

Linking Gene Ontology

and Pathways

Jin Ok YangKorean BioInformation Center

6th InCoB 2007

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

KOBIC (Korean BioInformation Center) The national bioinformatics center of Korea Integration of diverse biological information

Genome information Biodiversity information Bioresource information

Bioinformatics training

International exchange program Collaborative Development of bioinformatic tools

Bioportal (Biowiki) Biopipeline (Bioworkflow engine)

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

BioWiki Wiki

• a web technology that enables anyone to create and update website contents

• suited for developing online knowledge bases (e.g., Wikipedia )

BioWiki• To adopt the wiki paradigm in biology• Collaborative development of biological knowledge

bases• BioWiki Contest ( http://biowiki.net )

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

BioPipe (http://www.biopipe.net)

Design View

Ontology View

Monitoring View

Toolbar

Drag the module from the list and drop it into the design view. Drag the module from the list and drop it into the design view.

• BioWorkFlow Engine

• No installation required

• Drag & Drop, and then Connect

• BioPipe Contest !!– Aug 15th ~ Sep 20th

– Open free Web 2.0

• BioWorkFlow Engine

• No installation required

• Drag & Drop, and then Connect

• BioPipe Contest !!– Aug 15th ~ Sep 20th

– Open free Web 2.0

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

GS2PATH:

Linking Gene Ontology

and Pathways

Jin Ok YangKorean BioInformation Center

6th InCoB 2007

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Background

Efforts on analyzing functional relationships among gene

sets with GO term and pathways

Gene Ontology (GO) Term based analysis Analysis

focused on function

GO term related pathways More useful information

How do you

interpret the gene

set ?

GO & Pathways

GO & Pathways

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Gene set enrichmentEnrichment Test

Means test to investigate which specific GO term the given gene

set has

P-value for GO term was calculated by using hyper-geometric

probability

Gene set enrichment

Derives its power by focusing on gene sets, that is,

groups of genes that share common biological function,

chromosomal location, or regulation

Evaluates microarray data at the level of gene sets

which are defined based on prior biological knowledge

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Introduction: GO

GO databases and tools

GO term was used mostly to

analyze data sets to identify

significant biological changes

Pathways also can be exploited to

find functional relationships in genes

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Introduction: Pathways

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

GS2PATHA system to find gene set enrichment in

each Gene Ontology (GO) terms and map

the part of gene set on GO term into

biological pathways (KEGG  and BioCarta)

An integrated search tool for analyzing

the functional relationships in gene sets and

for providing comprehensive results

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

FeaturesFunctional relationships between GO term and

pathways

Hyper-geometric test for gene set enrichment

Dual search for up- and down- regulation gene set

Various filtering options for GO termsthe number of descendant node, evidence of GO terms

and statistical values mapping gene set in each GO term

User-specified coloring for genes onto pathways

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Implementation (1/3)

GS2Path consists of

one internal database (mapping

database)

four components

Query Processor, GO Accessor, KEGG

Accessor, and BioCarta Accessor

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Schema of internal mapping DB

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Architecture

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Implementation (2/3)Query Processor

receives a user query

Converts query into gene related information

distributes it to the other components, waiting for receiving

results

from them

GO Accessor

retrieves statistical values mapping gene set in each GO terms to

KEGG and BioCarta Pathways

Calculates P-value using cumulative hyper-geometric distribution

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Implementation (3/3)BioCarta and KEGG Accessor

retrieve results from BioCarta and KEGG databases,

respectively

To support user-specified coloring,

For KEGG, exploiting the web service API (SOAP/WSDL) of

KEGG

For BioCarta, no supporting user-defined coloring API. Thus,

after retrieving the image of a pathway from BioCarta database,

we color genes in the image on-the-fly.

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

GO Term based Pathways Analysis

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

SearchGene set enrichment test in organism

total profile: GO, KEGG and BioCarta

Single or two parts analysis (up and

down regulation)

Pathway viewer for KEGG and

BioCarta

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

InputDatabase

GO category Biological Process Molecular Function Cellular Component

Pathways: KEGG and BioCarta

OrganismHuman, Mouse, Rat, and Yeast

Gene ID list

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Test

Enrichment testP-value: Hyper-geometric probability

FDR (False Discovery Rate)Adjustment of p-value

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

FilteringGO Term

EvidenceSlimNumber of genes in termP-value

Pathways: KEGG and BiocartaNumber of genes in termP-value

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Example: microarray clustering data

Part A

Part B

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Interface

Select Organism

Put the gene set

Select GO category or Pathways

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Click

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Retaining only GO

terms having at least 5

genes

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Select customized colors

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

Genes colored in KEGG and BioCarta

>>> Korean BioInformation Center>>> Korean BioInformation Center

>>> >>> KRIBBKRIBB Korea Research institute of Bioscience and BiotechnologyKorea Research institute of Bioscience and Biotechnology

ConclusionUsing Gs2path, users

Get the integrated Gene Ontology terms and

pathways information together

Filter the results with various conditions

Capture relationships between Gene Ontology

terms and Pathways

Available at

http://array.kobic.re.kr:8080/arrayport/gs2path/