Arabidopsis Reactome is based on the Reactome system so please refer to the human Reactome User's Guide shown below



Reactome User's Guide



Introduction

This document is designed to get you (the new user) up and going with Reactome, a knowledgebase of biological processes. This is not a comprehensive guide, but should provide you with enough information to search and begin using the database. We encourage you to read through it and contact us with any comments or questions that you might have.
-The Reactome Staff

Getting started

What is Reactome?
What types of information does Reactome contain?
How is Reactome data organized?
What do Reactome stable identifiers allow me to do?
In what other formats may I view/export Reactome events?
How do I search Reactome?
How is electronic inference used to predict events in Reactome?
What is the Reactome Pathfinder?
What is the Reactome Skypainter?
How can I see who has contributed knowledge to Reactome?
How can I see the topics that will be annotated in future Reactome releases?
How can I download Reactome data?
How do I cite Reactome?
How do I link to Reactome?

Viewing Reactome data

A complete list of the pathways contained within Reactome can be seen on the Table of Contents (TOC) page. The pathways are grouped under broader topics which are presented in the "Pathway Topic List" on the Front page. Above the list of pathway topics is a "birds-eye" graphical view of the organization of these. A full description of each pathway (or pathway sub-event) is provided by individual Event Pages. A description of individual molecules and complexes is provided on separate pages that link out from the Event pages.

The Reactome Frontpage contains two sections that are used to view data:

The Pathway Topic List provides a list of pathway topics currently represented in Reactome (for a more complete list of pathways contained in Reactome, see the TOC) .

The Reaction Map provides an interactive graphical representation of Reactome pathways. A pathway is depicted as a set of interconnected arrows, each representing a reaction (e.g., "Formation of Cyclin E1:Cdk2 complexes"; "Phosphorylation of Cyclin E1:Cdk2 complexes"). Each of the reaction arrows is linked into pathways as dictated by the order of reactions in that pathway. Although human reactions are shown by default, the user can select from among the other available species in the "drop down" menu above the Reaction Map as shown above.


"Mousing-over" a Topic name, such as the Apoptosis, highlights the graphical icon of the reactions included in the Apoptosis pathways on the Reaction Map. The "moused-over" Topic is displayed as a series colored reaction arrows. A pale halo of background color similar to that of the overlying arrow(s) is added to facilitate visualization of these arrow(s) within the map) as shown above.

A color coded key under the Reaction Map describes the meaning of the different arrow colors. If the reaction has been experimentally confirmed in the selected species, the arrow is blue, if the reaction has not been confirmed directly but has been inferred manually from another reaction (either in the selected species or another species) the arrow is pink, if the reaction has been inferred computationally, the arrow is green. Reactions that are not considered part of the selected Pathway Topic are displayed as grey arrows. Note that each Reactome event is represented by only one arrow in the map. When a reaction in one pathway is preceded by a reaction from another pathway, this is indicated by a thin grey line between the reactions in the two pathways. In example shown below, the red arrow on the right points to the reaction "glutaryl-CoA +FAD=>crotonyl-CoA+ FADH2+CO2" (name not shown here), within the pathway Metabolism of amino acids and related nitrogen-containing molecules. This reaction is also the preceding reaction for the reaction "Crotonoyl-CoA+H20<=>(S)-3-Hydroxybutanoyl-CoA" (red arrow on right) in Lipid Metabolism. Thus, these two reactions are associated with a grey arrow. Mousing-over an individual reaction arrow displays the name of that reaction and highlights, within the Pathway Topic List, the name of the pathway(s) in which this reaction occurs.


Selecting a pathway in the Pathway List or an individual reaction in the Reaction Map directs the user to the Event Page upon which the reaction map been has zoomed to display the pathway of interest in greater detail.The Event/Molecule Page provides a detailed description of the selected molecule, pathway or reaction.

The Event page
Formats:
The information on each page can be viewed in one of three formats:

1. The Classic format with event hierarchy in sidebar. This is the default format.

2. The Sectioned format (with separate sections for the Reaction Map, Event Hierarchy, Event Diagram and Details sections)

3. Instancebrowser format(a format in which selected event or molecule is displayed as a database instance and the values of each of its attributes are displayed.)

The "Classic" view format:
In the Classic view format, the page is divided into 3 sections, the Reaction Map at the top, the Event Hierarchy panel on the left and the Event/Molecule Description on the right. The Event/Molecule Description, Event Hierachy, or Reaction Map panels can be hidden/displayed by clicking on the -/+ symbol above each panel.

Reaction Map: The Event Page view of the Reaction Map provides additional options for viewing pathways/reactions within the map. Three buttons at the top of the panel allow the user to zoom in or out on the map or to redefine the center of the map by shifting focus to a different map location. In addition, four scroll arrows allow the user to navigate up and down or side to side within the map. In this view, it is also possible to see the name of any reaction in the Reaction Map by mousing-over it. However, only the event that is the subject of current event page is ever highlighted on the map.

Event hierarchy panel: This panel shows the hierarchical relationship between sub-events (i.e. pathways and reactions) within a selected pathway. For example, For example, the pathway "Thrombin-activated activation cascade" is subdivided into two pathways: "Thrombin-mediated activation of PARs" and "G-protein cascades". .


-The selected pathway in the event hierarchy panel is highlighted in bold text.

-To expand/or condense the hierarchy view in the left panel, click on the +/- button to the left of the event in the hierarchy.

-If the selected event is a component of multiple pathways (not shown here), each pathway involving that event will be shown with the event of interest highlighted in bold. Scrolling up and down will allow viewing of all instances of that event.


Event description: The event description contains a title and often a text description and/or a figure. The text description is associated with references where appropriate. In addition, an event may be described by the following categories of information. Note that a description /definition of each of these categories, and others not listed here, is provided on the live pages by mousing-over the category name.


Information categories:

Stable identifiers are currently available for reactions, pathways, regulator events and physical entities (molecules compounds,complexes)
*Input the physical entities (molecules/complexes) that take part in a given event.
*Output: the physical entities (molecules/complexes) that are produced by a given event.
*Catalyst: the physical entity that catalyzes the reaction. 
*Essential catalyst component: the precise component within a catalyst complex (or domain within a simple catalyst) that enables the reaction to occur.
GO molecular function: the Gene Ontology term that represents the activity of a catalyst within the given reaction. For further description of the Gene Ontology, click here. A description of the GO term can be viewed via the GOID which links out to the QuickGO Gene Ontology browser.
Represents GO biological process: (N/A in above event) the Gene Ontology (GO) Biological Process term that corresponds to the Reactome event (if one exists). A description of the GO term can be viewed via the GOID which links out to the QuickGO Gene ontology browser.
Preceding event(s): a list of events that occur prior to the event being viewed.
Following event(s): a list of events that occur after to the event being viewed.
Cellular compartment:the location within cell at which event occurs.
References:a list of supporting references each of which hyperlinks to corresponding PUBMED abstract (when applicable).
Taxon: the name of the species in which the event occurs.
This event is deduced on the basis of event(s) in other organism(s): this indicates that event has not been experimentally demonstrated in humans, but has been inferred on the basis of data acquired for another species. The species in which the event has been demonstrated is listed here.
Equivalent event(s) in other organism(s): this provides links to events in other species that are either confirmed to occur in a very similar way in both species, or have been inferred by electronic annotation. Electronically inferred events point back to the original event with the link "This event is deduced on the basis of event(s) in other organism(s)". They also have the 'evidenceCode' slot filled in with 'inferred by electronic annotation' (view in instancebrowser).
Participating molecules: a list of all molecules that participate in the selected event as well as all of its sub-events.

For example:


The list of participating molecules for the event "mRNA 3'-end processing" include those molecules involved in the component events: "Cleavage of mRNA at the 3'-end" and "mRNA polyadenylation". A participating molecule may be either a simple molecule or a complex and it may function in a reaction as the input, output, catalyst, or regulator. In the case that the participating molecule is a protein, direct links (if available) are provided to its corresponding UniProt, ENSEMBL, Entrez Gene, KEGG gene, OMIM entries through the , , , and hyperlinks, respectively that are found adjacent to the participating molecule name.

In the case of small molecules, links are provided to ChEBI, KEGG COMPOUND and PubChem and appear as , and and hyperlinks after the name of the "small molecule".

*Note: A detailed description of each Reactome molecule is displayed on an independent page that is linked to the molecule name.


Sectioned view format:
In the sectioned view format, the Event page is divided into four sections, the Reaction Map at the top, followed by the Event Hierarchy, the Event Diagram and finally the Details section.

The +/- symbol in a box to the left of each section name allows the user to show or hide that particular section of the page. The Event Description, Event Hierarchy, or Reaction Map panels can be hidden/displayed by clicking on the -/+ symbol above each panel.

Reaction Map: In the Reaction Map, pathways are depicted as a set of interconnected arrows, each representing a reaction. Each reaction arrow is linked into pathways as dictated by the order of reactions in that pathway. Three buttons at the top of the panel allow the user to zoom in or out on the map or to redefine the center of the map by shifting focus to a different map location. In addition, four scroll arrows allow the user to navigate up and down or side to side within the map. In this view, it is also possible to see the name of any reaction in the Reaction Map by mousing-over it. However, only the event that is the subject of current event page is ever highlighted on the map.

Event hierarchy panel: This panel shows the hierarchical relationship between sub-events (i.e. pathways and reactions) within a selected pathway. The symbol indicates that the adjacent event is a reaction and the symbol indicates that it is a pathway. For example, the Notch signaling pathway above is subdivided into 7 component subpathways.

-The + symbol indicates that a pathway can be "unfurled" further to reveal its component events (or that a generic reaction can be "unfurled" to reveal the specific reaction instances.) Likewise the - symbol indicates that all of the existing sub-events for the pathway/reaction are shown. Clicking on the +/- symbol unfurls/hides the sub-events respectively. Absence of a + or - symbol next to an event indicate that this event has no sub-events.

The text color for a given event in the hierarchy indicates whether the event has been confirmed experimentally (blue) manually inferred from another given event for which there is direct evidence (pink) or electronically inferred (green).

-The selected pathway is highlighted in bold text within the hierarchy. A set of 4 buttons at the top of the hierarchy panel allow the user to 1.open the event hierarchy from the top-most level pathway to which the selected event belongs down to the event itself to 2. Open the hierarchy containing the selected event completely, down to the end of the pathway that the selected event belongs to. 3. Close the entire hierarchy down ( to show just the top-most level pathway to which the selected event belongs.)

- If the selected event is a component of multiple pathways (not shown here), each pathway involving that event will be shown with the event of interest highlighted in bold. Scrolling up and down will allow viewing of all of the instances that event.

Event Diagram: The Event diagram provides a graphical representation of Reactome reactions. The reaction currently being viewed ("current reaction") is represented as text in the center of the diagram. The input and output molecules are represented by colored boxes positioned to the left and right of the "current reaction" respectively. Grey boxes represent proteins, white boxes are small molecules, orange boxes are complexes and pink boxes are generic entities (i.e.: Okazaki fragment, dNTP). Inputs and output molecules are shown leading into and out of reactions with black arrows. Catalysts are shown as boxes that connect to the "current reaction" with a red arrow (Note that a box in the input column that connects to the "current reaction" with a red arrow indicates that the catalyst is also an input for that reaction.). The reactions that precede and follow the current reaction are displayed as text at the right and left of the diagram. The input, output, catalyst and reaction glyphs hyperlink to their corresponding molecule/event description pages.

Details: The Details section provides a description of the Event or molecule that is the subject of the page. This section contains a title and often a text description and/or a figure. The text description is associated with references where appropriate. In addition, an event may be described by the following categories of information. Note that a description /definition of each of these categories, and others not listed here, is provided on the live pages by mousing-over the category name.

Information categories:

*Input the physical entities (molecules/complexes) that take part in a given event.
*Output: the physical entities (molecules/complexes) that are produced by a given event.
*Catalyst: the physical entity that catalyzes the reaction. 
*Essential catalyst component: the precise component within a catalyst complex (or domain within a simple catalyst) that enables the reaction to occur.
GO molecular function: the Gene Ontology term that represents the activity of a catalyst within the given reaction. For further description of the Gene Ontology, click here. A description of the GO term can be viewed via the GOID which links out to the QuickGO Gene Ontology browser.
Represents GO biological process: (N/A in above event) the Gene Ontology (GO) Biological Process term that corresponds to the Reactome event (if one exists). A description of the GO term can be viewed via the GOID which links out to the QuickGO Gene ontology browser.
Preceding event(s): a list of events that occur prior to the event being viewed.
Following event(s): a list of events that occur after to the event being viewed.
Cellular compartment:the location within cell at which event occurs.
References:a list of supporting references each of which hyperlinks to corresponding PUBMED abstract (when applicable).
Taxon: the name of the species in which the event occurs.
This event is deduced on the basis of event(s) in other organism(s): this indicates that event has not been experimentally demonstrated in humans, but has been inferred on the basis of data acquired for another species. The species in which the event has been demonstrated is listed here.
Equivalent event(s) in other organism(s): this provides links to events in other species that are either confirmed to occur in a very similar way in both species, or have been inferred by electronic annotation. Electronically inferred events point back to the original event with the link "This event is deduced on the basis of event(s) in other organism(s)". They also have the 'evidenceCode' slot filled in with 'inferred by electronic annotation' (view in instancebrowser).
Participating molecules: a list of all molecules that participate in the selected event as well as all of its sub-events.

For example:


The list of participating molecules for the event "mRNA 3'-end processing" include those molecules involved in the component events: "Cleavage of mRNA at the 3'-end" and "mRNA polyadenylation". A participating molecule may be either a simple molecule or a complex and it may function in a reaction as the input, output, catalyst, or regulator. In the case that the participating molecule is a protein, direct links (if available) are provided to its corresponding UniProt, ENSEMBL, Entrez Gene, KEGG gene, OMIM, UCSC Genome Browser, and REFSEQ entries through the , , ,,, and hyperlinks, respectively that are found adjacent to the participating molecule name.

In the case of small molecules, links are provided to ChEBI and KEGG COMPOUND and appear as and hyperlinks after the name of the "small molecule".

*Note: A detailed description of each Reactome molecule is displayed on an independent page that is linked to the molecule name.


The Instancebrowser view format:

This display describes the selected event or molecule as a database instance and provides the values of each of its attributes. For a description of each attribute, see the Reactome schema The instancebrowser view of the reaction "Notch 1 heterodimer binds with a Notch ligand in the extracellular space" is shown here:

Changing the page viewing format:

A small menu bar found at the bottom of every page provides the option to [Change default viewing format]. Clicking here displays the following dialog box


which allows the user to select the page format of the displayed information.

Viewing/exporting Reactome events in other formats:

It is possible to export any Reactome Event in a number of different formats. A small menu bar found at the bottom of every event page lists the formats available and is described below.


More comprehensive sets of Reactome data and tools are also available on the downloaded page. This includes the complete Reactome textbook of biological processes in PDF or RTF format, the complete set of human reactions in Reactome (in SBML level 2 or BioPAX level 2 format), and a list of human protein-protein interaction pairs. For more information about SBML, click click here. For more information about BioPAX click click here.

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Searching Reactome

Simple searches

The simple search window for Reactome is located just below the menu bar on each Reactome page.


The query term/phrase is entered in the central (empty) window of this search bar. Using the drop-down menus within this search bar, the user can specify a number of search parameters. The first menu allows the user to choose the fields of information that will be searched. The second menu specifies how the text that is entered will be searched (i.e. using all words entered, or any one of the words etc.)For more information on search modes, click here.Finally, the species is selected through the third menu.


A search across all categories using human Cdc6 results in 38 hits in 5 different categories.


Clicking on the number to the right of the category of interest, i.e. Event (pathways/reactions) displays a list of the hits in this category.


The events of interest are then selected by checking the corresponding box(es). The user can then choose to view the selected instances in different formats. For example, as a list, as it would be seen in the Eventbrowser view described above, as an attribute<->value pair list (i.e. the format that would be seen in the Instancebrowser view ) or as a table. The tabular form is particularly useful if the data is to be copied/pasted into a spreadsheet.
For more Simple search examples, see below.

Extended search

The Extended search form can be accessed via the Extended search button located in the main menu bar on all pages. This search method allows more specific schema-based queries for particular types of Reactome data. Notably, this option allows searching for records (instances) in the database by multiple field (attribute) values. Queries are combined together with AND. For example, a query to retrieve all reactions which consume ADP and produce ATP would be formulated by selecting class Reaction, then selecting field name input and entering ADP into the query box, then selecting field name output on the next row and entering ATP. Note that the several possible search modes. more information on search modes, click here.


Search examples

  1. How can I find out more about my favorite process in Reactome?

In the simple search bar at the top of the page, select "process" in the first drop-down menu. Then choose "with exact phrase" in the second menu if the name of the process is widely accepted and uniformly used in the literature otherwise, choose a less stringent search mode such as "with all words". Next, enter the name of the process of interest such as "mRNA capping" into the text slot, select the species and hit GO!


In this case, a single pathway, "mRNA capping" matched the query phrase. Thus, the Event page for this pathway is displayed as the search result (shown below is the top part of this page).


If this searching approach fails, try to identify a Gene Ontology term that corresponds to the process that you are interested in and then use this term to search for Reactome events that may be cross-referenced to this GO term as described below.

  1. How can I find out more about my favorite protein in Reactome?

In the Simple search bar at the top of the page, select "molecule" in the first drop-down menu and choose "with exact phrase" in the second menu. This will search through the primary names and synonyms of all molecules and complexes. If this doesn't hit the protein of interest, see Search tips below.

  1. How can I use a GO Biological Process term to search Reactome?

In the Extended Search form, Select "GO_BiologicalProcess" in the Restrict search to a class slot, "display name" in the field name window and the name of the GO term in the value slot. Use the "exact match" mode if you have the exact GO term name. To search GO for the term of interest, use the AmiGO browser at the Gene Ontology website.

  1. What written information does Reactome have involving my topic/protein of interest?

In the Simple search bar at the top of the page, select "summation" in the first drop-down menu. Then choose "with exact phrase" in the second drop- down menu for a very specific search on that term or phrase. Alternatively, choose a less stringent search mode such as "with all words" to search hits that include the all the query words in no particular order.  Enter the term or phrase in the text entry window, select the species and hit GO

Searching Tips

What if I can't find the gene/protein that I am looking for?

  1. You may be searching on a name that is not currently stored as either the primary name or synonym for that protein.
    Try finding the UniProt name or identifier and search on this.
  2. Your gene/protein name may contain symbols that are causing trouble.
    If the name you are searching on contains symbols such as - , '
    Try stripping the symbols from the name and performing the search in full text Boolean mode. If the spacing/positioning of the symbols within the query does not match that of the UniProt name, the entry will not be retrieved.
    For example, if you are searching for Orotidine 5'-phosphate
    Orotidine 5' -phosphate: is not found in any of the three searches.
    +Orotidine +5 +phosphate: retrieves the entry.

Reactome Tools

1. The Reactome Pathfinder

The Pathfinder tool is used to identify or discover pathways that connect a given input and one or more output molecules or events. When multiple output molecules/events are designated, the shortest path is displayed. (see notes on browser/plugin requirements below). A link to the Pathfinder tool can be found in the main menu bar on each page.

For example, to search for a human pathway between the molecule G6PD and xylulose 5-phosphate, G6PD is entered as the input and the two reactions as outputs. Very common molecules are excluded to reduce the number of irrelevant pathways generated. These are listed as "non-connecting compounds". Additional molecules can be excluded by adding their names to the precompiled list.
Hitting GO! will search Reactome for the start and end compounds/events entered.


A drop-down list of hits to the entered names is provided. Here G6PD dimer is selected as the input and the reactions "D-ribulose 5-phosphate (cytosol)" is selected as an output. The search is initiated by clicking on GO!


If a path is found, a list of the events and molecules connecting the selected inputs is shown at the bottom of the page. The path between the entered input molecules is displayed in the reaction map. Reactions are highlighted in red and the small molecules in green.


*Note: The graphical display of the path requires your browser to have a java (version 1.3) plugin and does not work with Netscape 4.x.

2. The Reactome Skypainter


Skypainter is a tool to determine which events (reactions and/or pathways) are statistically overrepresented in a set of genes as specified by submitted list of identifiers. In other words, given a list of genes, Skypainter can identify common events for these genes.

Given a set of M genes which participate in an event, the total of N genes (for the given species) that Reactome is aware about, and given the submitted list of K genes of which X genes participate in the given event, skypainter calculates (by performing the hypergeometric test) the probability of picking X or more genes involved in the given event purely by chance. Hence a low probability suggests that participation in a given event is what the genes in the submitted list have in common. Note, however, that the probabilities as reported by Skypainter are not corrected for multiple testing arising from evaluating the submitted list of genes against every event for the given species.

Identifiers which can be used are UniProt accession numbers and ids, GenBank/EMBL/DDBJ protein ids, RefPep, RefSeq, EntrezGene, MIM, Affymetrix and Ensembl protein, transcript and gene identifiers. All purely numeric identifiers, such as from MIM and EntrezGene have to have the abbreviated database name and colon prepended to them, i.e. MIM:602544, EntrezGene:55718.

The colour of each reaction arrow on the reaction map according to the number of genes in the submitted list participating in the given reaction.

Similar functionality, i.e colouring reactions according to the number of times the reaction is hit by the identifiers in the submitted list, is also available for small molecule identifiers from ChEBI and KEGG COMPOUND identifiers (e.g. ChEBI:2359, C00002), Enzyme Commission (EC) numbers (e.g. 1.1.1.1) and Gene Ontology (GO) accession numbers (e.g. GO:0004672). GO cellular component accession numbers can be used to highlight reactions involving molecules with compartment with given accession number or which themselves correspond to the given GO cellular component term. GO molecular function accession numbers highlight reactions which are catalysed by the activities they specify. GO biological process accession numbers highlight reactions which either correspond or are components of pathways corresponding to the given GO biological processes. Please note that the overrepresentation analysis is not performed for those identifiers.

If the identifiers are followed (separated by space or tab) by a numeric value, the colouring will be done according to the average of the numeric values of all identifiers linked to the reaction. A time series can be displayed as an animation by providing multiple values (on the same line, separated by a single space or tab) for each identifier. This feature can be used, for example, to produce a "movie" on the basis of micro-array expression analysis a time series. Please note that the overrepresentation analysis is not performed in this case.

To see an example of the Reactome reaction map painted using a test set of identifiers, click on the hyper-linked word "identifiers" in the data entry box above. To see an example of the Reactome reaction map painted using a test set of identifiers, click here . To see an example of the reaction map painted using a test set of identifiers with values (producing a "movie") click here

We also have documentation providing detailed technical information on linking from your own web pages to the SkyPainter, e.g. for displaying expression, proteomics or metabolomics data projected onto Reactome pathways.