Reactome Introduction

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    www.reactome.org

    A curated database of biological pathways

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    Why are pathways important?

    Deep response

    Pathways are how cells work - going beyond the parts list

    into mechanisms at the cellular level is a fundamental

    advance in knowledge.

    Shallow response

    Lots of Omics datasets require data integration.

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    Reactome is

    Manually curated and peer-reviewed database of pathways and

    processes in human biology

    Open source and open access

    Basic Unit of Reactome = Reaction

    Extensively cross-referenced

    Infer orthologous events in non-human species (Data Expansion)

    M/O Reactomes:Arabidopsis, Gallus, Drosophila, (Oryzae)

    Provides tools for browsing, searching, analyzing and visualizing

    pathway data Pathway Analysis, Expression Overlay, Species

    Comparison, Biomart

    Data Portability BioPAX, SBML, PSI-MITAB, etc.

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    Visualization

    www.reactome.org

    4

    Reactome Home Page

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    Data Visualization and Analysis

    Human EGFR Pathway

    ID M

    apping, Over-representation and expression analysis

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    Increasing Coverage:

    Reactome Functional Interaction Network

    Data Sources

    Pathway databases

    Protein-protein interactions

    Shared GO terms

    Gene co-expression dataTranscription factors/targets

    Literature mining

    10,956 proteins (58% in pathways)

    209,988 interactions (47% in pathways)

    46% coverage of UniProt

    Figure: 15% of the combined network

    Networks provide better coverage and when combined with pathway information can offerclues to mechanism.

    Add non-Reactome data sets to create a corona of interaction data around each pathway.

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    Human EGFR Pathway

    MolecularInteraction Overlay PSIQUIC WS

    PSICQUIC Registry

    APID

    BIND

    BioGrid

    ChEMBL

    DIP

    InnateDB

    IntAct

    iRefIndex

    MatrixDB

    MINT

    MPIDB

    Reactome

    Reactome-FIs

    STRING

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    Data Exchange Formats

    Promote data integration, analysis and visualization.

    PSI MITAB representing interaction data* (*infer interactions from the complexes

    and reactions).

    SBML representing models of biochemical pathways, reactions and networks.

    BioPAX used for representing pathway and network data.

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    Integrative Data Analysis using Reactome Functional

    Interaction Network Cytoscape Plug-in

    Guanming Wu, Irina Kalatskaya, Christina Yung

    Expt/Clinical DataReactome F.I. Network

    Extract mutated, over-expressed,down-regulated, amplified,

    deleted genes

    Disease/Canc

    er

    Subnetwork

    Disease/Ca

    ncer

    Modules

    Apply

    clusteringalgorithms

    Pathway

    Annotation

    Datasets

    T2D

    GBM

    Ovarian Cancer

    Breast CancerProstate Cancer

    TCGA

    ICGC

    Create a Biological Hypothesis!

    Predict Disease Gene Function

    Classify Patients & Samples

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    Programmatic Access

    Application programming interfaces (API) are important to connect andautomate data exchange between local programs and databases.

    BioMart API

    MySQL/Perl API

    MySQL/Java API

    SOAP/WSDL

    Flat files

    Database dumps

    Local site install

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    Uber-portal Integration (Data Warehouses) and other exports

    OtherData Exports

    Gene Ontology, Protein Ontology

    HapMap and UCSC Genome Browsers

    GSEA

    WikiPathways, Wormbase, PDB

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    Summary

    Pathway databases are an integral part of the scientific enterprise.

    Reactome has deployed a user-friendly web site that promotes

    integrated research on pathways and networks.

    Data visualization

    Data analysis

    Data expansion

    Data integration

    Data standards/exports

    Develop and distribute open software and standard operatingprocedures for the management of pathway information.

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    Credits

    OICR/CSHL NYU EBILincoln Stein Peter D'Eustachio Ewan Birney

    Michael Caudy Shahana Mahajan Henning Hermjakob

    Marc Gillespie Lisa Matthews David Croft

    Robin Haw Veronica Shamovsky Phani Garapati

    Irina Kalatskaya Bijay JassalBruce May Steven Jupe

    Leontius Pradhana Nelson Ndegwa

    Guanming Wu Gavin OKelly

    Christina Yung Esther Schmidt

    Supported by grants from the US National Institutes of Health (P41HG003751) and EU grant LSHG-CT-2005-518254 "ENFIN