Transcript Pathway Generation Tool III - BIDD

Lecture 8: Pathway Development Tool III:
Pathway Studio: Software for Visualization and Analysis
of Biological Pathways
Y.Z. Chen
Department of Pharmacy
National University of Singapore
Tel: 65-6616-6877; Email: [email protected] ; Web: http://bidd.nus.edu.sg
Content
•
Pathway Studio overview
•
Pathway Studio usage
•
Methods and tools used by Pathway Studio
Pathway Studio Overview
Pathway Studio pathways analysis software helps
you to:
•
•
•
•
Interpret biological meaning from gene expression,
molecular interaction and other high throughput data
Build, expand and analyze pathways
Find relationships among genes, proteins, cell
processes and diseases
Draw publication-quality pathway diagrams
Website:
http://www.ariadnegenomics.com/products/pathway-studio/
Publication:
Nikitin et al. Bioinformatics 19, 2155-2157 (2003)
2
Pathway Studio Features
•
Desktop software
•
•
•
•
•
Build and visualize pathways
Analyze and curate pathways
Import and analyze gene & protein lists
Interpret microarray gene expression data
Analyze proteomics and metabolomics data
Website:
http://www.ariadnegenomics.com/products/pathway-studio/
Publication:
Nikitin et al. Bioinformatics 19, 2155-2157 (2003)
3
Pathway Studio Features
•
MedScan Technology
•
•
•
•
Search and mine the literature
Extract interactions from the literature
Build targeted data content
Database management system
•
•
•
ResNet database
Interrogate different species, multiple genomes
Supports public and commercial databases
4
Pathway Studio Features
• Pathway Visualization
•
Graphical user interface for drawing,
coloring, viewing, editing and
annotation of pathway and
relationship maps
•
Automatic layout algorithms
revealing pathway organization
•
Publication-quality illustrations in all
major image file formats
•
Export of pathways as clickable
HTML or XML files
5
Pathway Studio Features
• Pathway Analysis and Curation
•
•
•
•
•
•
Create your own pathways and produce
publication quality graphics and diagrams
Optimize views by filtering, pathway expansion,
and protein classification
Build pathways for gene lists imported from
microarray and other experiments
Display specific upstream and downstream
events
Find interaction paths among molecules, cell
objects and processes
Determine and identify common targets and
regulators for a group of proteins
6
Pathway Studio Features
• Molecular Interaction Networks from the
Literature
•
Analyze pathways with ResNet database,
compiled from PubMed abstracts and articles
•
Access more than 1,000,000 facts of
regulation, interaction and modification
•
Validate the facts by clicking on the link to an
original sentence, abstract or source
7
Pathway Studio Features
• Pathway Reconstruction Algorithms
•
"Build Pathway" is a search tool with flexible options
to navigate the network database and build
pathways. Choose from multiple algorithms for
assembling a pathway such as "find only direct
interactions", "find shortest paths", "find common
targets" or "find common regulators".
•
"Find relevant networks" - finds pathways related to
a list of molecules
•
Find differentially expressed networks (pathways) for
a microarray experiment
8
Pathway Studio Features
• Data Mining and Searches
•
•
•
•
•
•
Find all interacting molecules for a protein or other
biological entity
Find all networks/pathways for a query protein
Use context and field-specific database searches
Filter to see only specific types of biological objects to be
included in your pathway, such as proteins, complexes,
small molecules, cellular processes etc.
Filter to see only specific types of biological interactions
such as binding interactions, post-translational
regulation, expression regulation, enzymatic activity,
molecular synthesis, transport, and others.
Review original literature sources for every relation within
a pathway via direct links to PubMed abstract and exact
source sentence where each finding is referenced
9
Pathway Studio Features
• Import and Analysis of Gene & Protein Lists
•
Import/export gene and protein lists
•
Map gene lists on signaling and metabolic pathways, and
GO groups
•
Build and analyze pathways from imported lists
•
Work with protein IDs, names or aliases from various
sources: Unigene IDs, Accession Numbers, LocusLink,
Swiss-Prot, Affymetrix GeneChip® IDs, Gene Names and
Gene Symbols
10
Pathway Studio Features
• Literature Mining
•
Use integrated MedScan software to extract biological
interactions from scientific text
•
•
•
Mine PubMed and build pathways from extracted facts
Update pathways using data from recent publications
11
Pathway Studio Features
• Microarray Gene Expression Data Analysis
•
Import data from all popular microarray analysis software
packages
•
Reconstruct molecular networks from gene expression
and proteomics data
•
View how genes in a pathway are up or down regulated
through various biological states to identify key regulators
or targets of interest
12
Pathway Studio Features
13
Pathway Studio Usage:
Creating pathway from Input Protein or Other Info
Step 1: Downloading of a local database
•
The Download Database dialog box is displayed
automatically during the first start of the application
(including demo installations); it will be displayed in each
start of the application until a user successfully opens a
local database.
•
To download the latest version of the ResNet database
from the Ariadne web site, select the menu
Database>Download Database and choose the Download
Database from the Internet option. Select the ResNet
database from the list and press OK. The latest version of
the ResNet database will be downloaded to your
computer. 5
14
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 2: Open a Local Database
•
Open Pathway Studio. To open a database:
•
Open Local Database ; Call the Database>Manage
Databases>Open Local Database
•
In the Open Local Database dialog box that appears,
select a database and press Open;
•
The next time you start Pathway Studio, the last
opened database opens automatically.
15
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
•
Importing Lists of Proteins
•
•
•
•
Protein lists exported from several standalone
programs or received from an expression experiment
can be imported into Pathway Studio.
The software provides two tools that help you to import
a list of genes and find functional links and regulations
between proteins in the list.
The Import Protein List tool is available via the
Tools>Import Protein List menu. This tool helps you to
import the list of genes from your experiment and save
it in the database as a functional group
16
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
•
Importing Lists of Proteins
17
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
To import a list of genes, do the following steps:
•
Create a one column list of genes in Notepad
•
Copy the list into Clipboard
•
Call Tools>Import Protein List menu (Import Protein List dialog box appears)
•
Press Paste (The list appears in the dialog box)
•
Specify the appropriate ID types (LocusLink ID or another ID type)
•
Press the Lookup button to map these proteins to the IDs in the
database (descriptions appear for successfully mapped proteins, proteins not found are
shown as not found)
•
Press Import (List Pane opens and the list of proteins appears as a new group)
18
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
19
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Supported gene IDs:
•
Pathway Studio supports the identification strings (IDs) from the
following databases:
• LocusLink from NCBI2
• HGNC (HUGO Gene Nomenclature Committee3)
• GenBank IDs
• Affymetrix Probe IDs
• UniGene from NCBI4
In addition, you can import the list of protein names and aliases. While
importing, the software searches the ResNet protein database to match the
specified field to the record in the imported ID list. If the record has not been
found in the database, the program marks it as not found. Current ResNet
protein database contains records from human, mouse, and rat genomes.
Proteins from other organisms cannot be found in ResNet
20
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Importing Protein Network
•
The Importing of Protein Network tool is designed to store your
experiment data results and display a graphical representation of them
•
Examples of uses for this tool include a list of genes from your
expression experiment or a list of proteins from a scientific article.
•
The Import Protein Network can help you develop a hypothesis that
explains the molecular mechanisms of the protein regulation.
•
It searches the database of biological association networks to find
functional links and regulations between proteins in the list.
21
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Importing Protein Network
•
•
•
•
Menu: Tools>Import Protein Network
Create the two column list of protein IDs in MS Excel
Copy the list into Clipboard
Call the Tools>Import Protein Network menu (Import Protein Network dialog box
appears)
•
•
•
Press Paste (list appears in the dialog box windows, one column per window)
In the ID field, specify the appropriate ID types
In the Relation Type field, specify the relation type (You can specify one
relation type per importing session)
•
•
•
In the Direction field, choose the link direction (<–, —, –>)
In the Effect field, select the effect type (negative, positive, unknown)
Press the Lookup button to create a pathway (relation description appears for
•
those successfully Mapped relations)
Press the Import button (The pathway appears in the Pathway Pane)
22
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
23
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Import Wizard
24
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Import Wizard
25
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Import Wizard
26
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Importing Pathway
•
Call the Database>Import Wizard menu
•
In the Data Source dialog box, choose the Other Data option
•
In the Data Format dialog box, specify ResNet format as the type of
import you want to use
•
In the Data Files dialog box, press the Add button. Select the name and
location of the pathway file, and press the Next button
•
In the Preview dialog box, review the data designated for importing, and
press the Next button to start the import process (The imported pathway
appears as a new folder in the Database Pane with the pathway’s name corresponding to
the name of the file)
27
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Importing KEGG Pathway
•
KEGG files can be obtained from:
•
•
•
•
•
•
ftp://ftp.genome.ad.jp/pub/kegg/ligand/enzyme (Enzyme file)
ftp://ftp.genome.ad.jp/pub/kegg/ligand/compound (Compound file)
ftp://ftp.genome.ad.jp/pub/kegg/ligand/reaction (Reaction file)
ftp://ftp.genome.ad.jp/pub/kegg/ligand/glycan (Glycan file)
ftp://ftp.genome.ad.jp/pub/kegg/ligand/drug (Drug file)
To import the KEGG pathways in Pathway Studio, you should import all
these files (the Enzyme file, Compound file, Glycan file, Drug file ,and
Reaction file). After importing, the software creates the KEGG Pathways
folder in the Database Pane.
28
Pathway
Studio Usage:
Creating pathway
from Input Proteins
or Other Info
Importing KEGG
Pathway:
•
It is recommend to not
using the Pathway
Studio Download
KEGG from ftp option
Instead, download the
KEGG data from the
KEGG ftp site and then
use the ImportWizard
to import the data to
your database.
29
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Importing Expression and Other Microarray Numerical Data
•
The data file can be in Plain Text or MS Excel, CEL1, or GPR2 format.3
•
To import your data, call Expression>Import Expression Experiment
menu and choose format. Then, specify the location of the data file.
•
The imported data will be opened in the Import Expression Wizard.
Follow the steps provided with the Wizard system.
30
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 3: Importing data
Importing Expression and Other Microarray Numerical Data
•
•
•
In the window that appears next: 1) specify the column of the
data file that contains the Gene IDs, 2) specify the ID types used
in your experiment, and 3) press the Next button. By default, the
selections offered are either the Microarray ID or LocusLink ID type
31
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 4: Creating Pathway
•
Choose Database>New Pathway from the Main Menu, or
press the Create New Pathway button on the Database
Pane Toolbar
•
The Pathway named "New Pathway" appears in the User
Pathways Folder
•
To save a pathway, choose Pathway>Save Pathway
32
Pathway Studio Usage:
Creating pathway from Input Proteins or Other Info
Step 5: Analyzing Pathway
33
Pathway Studio Usage:
Pathway Analysis
34
Pathway Studio Usage:
Pathway Analysis
35
Pathway Studio Usage:
Pathway Analysis
36
Methods and Tools used by Pathway
Studio: MEDSCAN for Literature Search
37
Methods and Tools used by Pathway
Studio: MEDSCAN for Literature Search
38
Methods and Tools used by Pathway
Studio: MEDSCAN for Literature Search
39
Methods and Tools used by Pathway
Studio: MEDSCAN for Literature Search
40
Methods and Tools used by Pathway
Studio: MEDSCAN for Literature Search
41
Methods and Technology used by Pathway
Studio: MEDSCAN for Literature Search
42
43
44
Methods and Tools used by Pathway
Studio: RESNET Databases
•
The ResNet Databases represent different sets of precompiled information on biological relationships and
associations, interactions and facts which have been
extracted from the biomedical literature using MedScan.
There are several available ResNet databases:
•
•
•
ResNet 5 Mammalian Database - for Human, Rat and
Mouse
ResNet Plant Database - download through Pathway
Studio software
ResNet Targeted Databases - available from the
Download Center
45
Methods and Tools used by Pathway
Studio: RESNET Databases
RESNET Features
•
All extracted relations have linked access to the original
article or abstract
•
Synonyms and homologs are included to maintain gene
identity and to obviate redundancy in search results
•
Users can update ResNet as often as required using the
MedScan technology built into all Ariadne products
•
Updates are made available by Ariadne every quarter
46
Methods and Tools used by Pathway
Studio: RESNET Databases
RESNET Features
47
Methods and Tools used by Pathway
Studio: RESNET Databases
RESNET Features
48
Methods and Tools used by Pathway
Studio: RESNET Databases
RESNET Features
49
Methods and Tools used by Pathway
Studio: RESNET Databases
RESNET Features
50
Methods and Tools used by Pathway
Studio: RESNET Databases
RESNET Features
51
Methods and Tools used by Pathway Studio: RESNET Databases
RESNET
Features
52