Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 1
Guide to Building Networks in Pathway Studio – An Introduction
This guide will demonstrate basic steps in building networks for a protein or list of proteins or other entity types.
Please see Ariadne’s Pathway Studio support site for more training materials, including a self-guided Training Manual, Analysis Guides
(showing advanced work flows), and FAQs.
http://www.ariadnegenomics.com/support/pathway-studio-7/
A. Add protein(s) to a new pathway view, select the protein(s) (or other entity types) and open the
advanced building pathway wizard to access the algorithms for building different types of networks.
Open a new pathway view by selecting “New Pathway” from the Information Pane on the left .
Once you have added your desired proteins to the New Pathway view, select the proteins. Selected proteins/entities have a blue ring
around them. Open the Advanced building pathway wizard by selecting: Add > Advanced.
These useful short
cut menus for
building networks
will not be
demonstrated in
this tutorial.
Select the “Home” tab on the top of the
Information Pane to find the link to open a
New Pathway.
See the Training Manual, available on
Ariadne’s support site for more instruction on
how to search the ResNet database to find
entities or to import a list of entities and add
them to the New Pathway view.
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 2
B. Select the algorithm most appropriate for the desired resultant network.
C. Select the directionality of the relations, the entity type(s) and relationship type(s) for the desired
network.
Directionality of Relations
The select algorithm type dialog provides you with the
choices to:
· Add Neighbors: find entities directly connected to the
entity / entities selected on the network diagram from the
ResNet database.
· Add direct interactions: find the relationship between two
or more selected entities on the network diagram.
· Add shortest path: find relationships between two or
more selected entities on the network diagram, adding
entities as needed to form the relationship.
· Add common targets: find one or more targets that are
regulated by at least two or more of the selected entities on
the network diagram.
· Add common regulators: find one or more regulators that
regulate two or more of the selected entities on the
network.
· Add Neighbors from a group: find entities directly
connected to the entity / entities selected on the network
.diagram from a specified group.
Screen shot from Pathway Studio Desktop.
Pathway Studio Enterprise dialog also allows for number of common
targets or regulators to be specified.
All relationships, except binding, have directionality.
You can select upstream only relations or
downstream only relations or all relation types
(both).
You can include binding in with all upstream or all
downstream relations by simply selecting binding in
the Relation Type dialog in the following steps of
the wizard.
Next select the desired entity types and relation
types. Selection of network types and relations and
entity types are dependent on the specific biological
question to be answered.
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 3
Entity Types
Small Molecule – naturally occurring metabolites in mammalian cells (ResNet Mammal); also drugs and non-naturally occurring in
mammalian cell small molecules and metabolites (ChemEffect).
Treatment – non-chemical treatments and environmental conditions, such as cold shock.
Relation Types
PromoterBinding – a regulator that binds to the promoter of a gene.
ProtModification – a regulator that changes the modification of the target molecule, usually by a direct interaction such as
phosphorylation, glycosylation, acetylation etc.
MolTransport – a regulator that changes the localization of the target (molecular translocation, export, import etc.)
Protein – defined by Entrez Gene (represents both
genes and the gene products – proteins)
Cell Process – biological processes, most
coincide with Gene Ontology (container entity)
Functional Class – most functional classes
coincide with Gene Ontology. (container entity)
Disease – health conditions and disease terms
from MeSH
Complex – several polypeptides that form a
complex via physical interactions (container entity)
Protein, Functional Class and Complex are
frequently grouped together as they represent
overlapping concepts.
.
Regulation – changes the activity of the target by an
unknown mechanism (may be direct or indirect). This
is a less specific relation type than others provided.
ChemicalReaction – enzyme catalyzed reaction
involving small molecules.
Expression – regulator changes protein abundance
by affecting levels of transcript or protein stability.
DirectRegulation – influences target activity by direct
physical interaction (excluding promoter binding
interactions).
MolSynthesis – regulator changes the concentrations
of the target (usually a small molecule target).
Binding – direct physical interaction between two
molecules.
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 4
The following section gives some examples of network building work flows but does not show all possibilities of networks that can be built
using Pathway Studio.
D. Examples of biological questions and the wizard pathway building settings used to answer find the
answers in the ResNet database.
1. What are all the known associations with my protein in the ResNet database?
Add protein to pathway view and select.
Wizard settings: algorithm: add neighbors; directionality: both; entity type: check all; relation type: check all.
2. What cell processes is my protein involved in? Add protein to pathway view and select.
Wizard settings: algorithm: add neighbors; directionality: downstream ; entity type: cell process; relation type: regulation.
Style sheet: By Type Style sheet: By Effect (positive/negative/unknown)
The “by type” style sheet
colors relation types for
easy identification.
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 5
3. What proteins regulate the expression of my protein? Add protein to pathway view and select.
Wizard settings: algorithm: Add neighbors; directionality: upstream; relation type: expression & promoterbinding ; entity type: protein, or
protein/functional class/complex
proteins only proteins/complexes/functional classes
For ONLY transcriptional regulation use only the relation type “promoterbinding”.
It is common to group “proteins” “complexes” and “functional classes” together when examining protein mediated activities.
4. Do any proteins modify (ex. phosphorylate, dephosphorylate etc.) my protein? Add protein to pathway view and select.
Wizard settings: algorithm: add neighbors; directionality: upstream; relation type: directregulation; entity type: proteins or proteins/functional
class/complex
DirectRegulation describes events where regulation
of a protein (such as modification) occurs through a
direct physical interaction.
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 6
5. Do any miRNAs regulate my protein? Add proteins to pathway view and select.
Wizard settings: algorithm: add neighbors from a group - select the desired group (Ariadne Ontology > Molecular Function > miRNA);
directionality: upstream; entity type: proteins; relation type; all
miRNAs are represented as proteins in the ResNet database. See the “Introduction to miRNA Analysis in Pathway Studio” for more
information about working with miRNA data and importing predicted miRNA relations into your database. miRNA regulators can also be
identified through the sub-network enrichment algorithms.
6. Are my proteins associated with any similar diseases? Add proteins to pathway view and select.
Wizard settings: algorithm: add common targets; entity type: disease; relation type: regulation
The “Common targets” algorithm means a target for two or more members of the selected group (desktop).
Common target thresholds can be adjusted for Enterprise users.
Darker lines represent more references for a relation. The higher the number of references for a relation, the more times it is described in the literature and
the more confidence you can have in the relationship.
Style Sheet:
By Type
Style Sheet:
By Reference
Count
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 7
7. Are any of the proteins known to be associated with a specific disease also associated with a second disease?
Step 1: Find all the proteins associated with a specific disease. Add disease to pathway view and select.
Wizard settings: algorithm: add neighbors; directionality: upstream; entity type: protein; relation type: regulation
Step 2: Find all connections between the second disease and proteins associated to first disease. Add second disease to pathway view and select.
Choose: Add > Relations between Selected and Unselected.
8. Are any of my proteins known physically interact with each other proteins? Add proteins to pathway view and select.
Wizard settings: algorithm: direct interactions ; directionality: NA; relation type: binding and directregulation (can also include ProtModification);
entity type: NA
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 8
9. Are my proteins regulated by any small molecules? Add proteins to pathway view and select.
Wizard settings: algorithm: add neighbors; directionality: upstream; relation type: regulation/moltransport/expression/directregulation;
entity type: small molecule
10. If my proteins have no direct interactions, can I connect them through intermediate entities? Add both proteins to pathway view and select.
Wizard settings: algorithm: add shortest path: directionality: both; relation type: all; entity type: all
Filters can be more specific to identify only connections through specific entity types or through specific relations.
If “Find Shortest Path” is applied to a large number of selected entities, the calculation may take a long time to run.
[Type a quote from the document or the
summary of an interesting point. You can
position the text box anywhere in the
document. Use the Text Box Tools tab to
change the formatting of the pull quote text
box.]
DirectRegulation relations
only shown here.
Ariadne: Guide to Building Networks in Pathway Studio – An Introduction 9
11. (ChemEffect database only) Does my small molecule regulate any cell processes or diseases? Add small molecule to pathway view and select.
Wizard settings: algorithm: add neighbors: directionality: downstream; relation type: regulation; entity type: cell process and disease
12. (Plant database only) What proteins are associated with a specific plant trait? Add plant trait (cell process) to pathway view and select.
Wizard settings: algorithm: add neighbors; directionality: upstream; relation type: regulation; entity type: proteins
This guide provides an introduction to network building using Pathway Studio and ResNet. For more detailed information on how to use
Pathway Studio please visit our website at: http://www.ariadnegenomics.com/support/pathway-studio-7/
Here you can find a self-guided Training Manual that will provide more detailed information on network building, Analysis Guides
(showing advanced work flows), and FAQs.
If you have any additional questions about Pathway Studio, please feel free to contact Ariadne’s Technical Support at:
[email protected] or call us at 866.340.5040 (US and Canada toll-free) +1.240.453.6301 (Worldwide).
(Network results filtered for relations
with 10 references or greater in this
figure.)
Style sheet: “By Effect”
Plant traits are represented as
cell processes.