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The Reactome Knowledgebase

Eliot Ragueneau - Software Engineer�Krishna Tiwari - Curator & Biologist

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Background

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Motivation for Pathway Databases and Analysis

Nature 407(6805):770-6.The Biochemistry of Apoptosis.

“Caspase-8 is the key initiator caspase in the death-receptor pathway. Upon ligand binding, death receptors such as CD95 (Apo-1/Fas) aggregate and form membrane-bound signalling complexes (Box 3). These complexes then recruit, through adapter proteins, several molecules of procaspase-8, resulting in a high local concentration of zymogen. The induced proximity model posits that under these crowded conditions, the low intrinsic protease activity of procaspase-8 (ref. 20) is sufficient to allow the various proenzyme molecules to mutually cleave and activate each other (Box 2). A similar mechanism of action has been proposed to mediate the activation of several other caspases, including caspase-2 and the nematode caspase CED-3 (ref. 21).”

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Motivation for Pathway Databases and Analysis

Intuitive to Scientists:

Intuitive display for biological data.
Visualize multiple data types.
Computational methods available to automate analysis.

Pathway Analysis satisfy common “use cases” in biological research:

Identifying hidden patterns in gene lists.
Predicting the function of unannotated genes.
Establishing the framework for quantitative modeling.
Assisting in the development of molecular signatures.

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What is Reactome?

Open source and open access pathway knowledgebase

Dates to 2002 @ CSHL & EBI
Human pathways encompassing metabolism, signaling, gene regulation, and other biological processes
Every pathway is traceable to primary literature

Extensively cross-referenced to external bioinformatics databases
Provides software tools for browsing and visualizing pathway data and analyzing user data

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Data Model

Reactome is a reaction-based database
Explicitly describe biological processes as a series of biochemical reactions and events

Literature

(PubMed PMID)

location

(GO cell component)

protein (UniProt)

molecule (ChEBI)

complex (GO/PRO)

ncRNA (miRBase)

disease variant (ClinGen, COSMIC)

drug (ChEBI, IUPHAR)

CatalystActivity

(GO mol function)

Output 1

Reaction

Input 1

Input 2

Output 2

Regulation

(GO biol process)

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Reactome supports multiple types of reaction

Phosphorylation

Binding

Dimerization

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Reactions connect to one another

OUTPUT

INPUT

CATALYST

INPUT OUTPUT

CATALYST

INPUT

OUTPUT

CATALYST

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Where does the data comes from?

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Reactome Coverage

20K human protein coding genes

11K Reactome

to do

Oprea TI, et al. Unexplored therapeutic opportunities in the human genome. Nat Rev Drug Discov. 2018 May;17(5):377.
10,092 human high confidence interactors from IntAct

7K no functional data [1]

10K interactors [2]

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PANTHER is used to identify model organism orthologs

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Reactome Website

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Searching with keyword

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Searching with keyword

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Pathway Browser

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Pathway Browser

Hierarchy

Graphics

Details

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Pathway Browser

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