The Biologically Relevant Analysis of Interaction Networks (BRAIN) is a set of algorithms for predicting and analyzing protein domain-peptide ligand interactions based on experimentally known binding evidence (e.g. from protein chip or phage display experiments).
BRAIN can be accessed as a Cytoscape plugin which reads peptide binding profiles and generates interactions displayed as a Cytoscape network.
BRAIN consists of a library or API, and of a Cytoscape plugin.
The BRAIN library holds the algorithms and methods for interaction prediction. This library is required to build the BRAIN plugin.
The BRAIN plugin is a way of running various BRAIN algorithms from the Cytoscape user interface. The plugin runs a prediction analysis and presents the results visually as an interactive Cytoscape network.
Latest Build Release
Dependencies: Additional JARs required by BRAIN - attachment:brainDeps.tar.gz
Installing the Plugin
- Java Runtime Environment (JRE) 1.5 or later is required to run BRAIN Plugin.
[http://www.cytoscape.org Cytoscape] 2.4.1 or later
Place brainPlugin.jar and brainlib_1.1.jar in the Cytoscape plugins directory (located in the Cytoscape program directory, e.g. /usr/local/bin/Cytoscape or C:\Program Files\Cytoscape_v2.4.1)
Extract and place all files from brainDeps.tar.gz into the Cytoscape lib directory (located in the Cytoscape program directory)
- Launch Cytoscape
Look in the Plugins menu for the BRAIN item. If you don't see it there, revisit the above steps to make sure all files are in the right place.
Running the Plugin
- Launch Cytoscape
Set analysis parameters from Plugins > BRAIN > Set Parameters
Start the BRAIN analysis from Plugins > BRAIN > Run BRAIN
Notes on Using BRAIN
BRAIN takes a set of query proteins and their respective peptide ligands, builds a PSSM-based profile for each protein, searches a protein sequence database for similar profiles, and returns a ranked set of proteins that are predicted to interact with the query proteins.
Each query proteins along with its experimentally determined peptide ligands should be represented as a [wiki:/PeptideFile peptide file].
BRAIN Plugin accepts one or more peptide file as shown in the example below. A peptide file describes a protein containing a specific domain, and provides known peptide ligands of this domain obtained by an experimental technique.
The peptide file consists of a Header Section that describes the protein and domain sequence, and a Peptide Section that lists and describes the peptide ligands.
Gene Name DLG1 Accession Refseq:NP_004078 Organism Homo Sapiens (Human) NCBITaxonomyID 9606 Domain Number 3 Domain Type PDZ Interpro ID IPR001478 Technique Phage Display High Valency Domain sequence KVVLHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDRIISVNSVDLRAASHEQAAAALKNAGQAVTIVA Domain Range 466-525 Comment PeptideName Peptide CloneFrequency QuantData ExternalIdentifier 1 XLHFWRESSV 66 2 XXRLWKQTSL 3 3 ILKIWRETSL 3 4 KRTIWRETSL 2 A KNLRSNSMLG 2 6 HLKFWRSTRV 2 7 AHSKWRSTSV 2 8 XXXHRRETTV 1 9 VISRWRQTSL 1 10 TTWLGRQTRV 1 11 SRSSYRETSV 1 12 XXXSRRETSV 1 13 RLFRYRETSL 1 B PIRKRWTMTL 1 15 XXXNHRETSV 1 16 KIVRWKNTSV 1 17 KHRTWYETSV 1 18 XXXXFKQTSV 1 19 ARPKWRTTRV 1 20 ALPRRRETSV 1
Describes the protein, domain, and experiment. Required fields are indicated with a *.
NOTE: This section is in a 2 column format. Field names must be separated from their values with a single TAB character. Multiple TABs or spaces are not accepted.
Gene Name:* An identifier that represents the gene or protein sequence. Not required to be unique.
Accession:* A space-separated list of database accession identifiers for the protein or corresponding gene.
Organism: Description of taxon of the protein.
NCBITaxonomyID*: Taxon identifier from NCBI's Taxonomy repository.
Domain Number*: A number that represents the position of the domain sequence within the protein. For proteins containing multiple instances of the domain, this number helps distinguish the position of these instances. Set to "0" if instance information is not known.
Domain Type:* The formal name of the domain, e.g. WW, PDZ, SH3.
Interpro ID: The Interpro database identifier for the domain.
Technique: The experimental method used to identify potential ligands of the protein.
Domain Sequence:* The amino-acid sequence of the domain region.
Domain Range: The amino-acid position range for the domain region within the protein.
Comment: Notes, additional information, personal comments pertaining to this file.
Describes the experimentally determined peptide ligands. The peptide sequences must be in multiple alignment format. The sequences should contain no gaps, and should be padded with the X symbol on both sides, where required, such that all sequences have identical length.
NOTE: This section is in a 5-column format. Column headers and values must be separated with a single TAB character. Multiple TABs or spaces are not accepted.
Required fields are indicated with a *.
PeptideName:* A unique numerical symbol assigned to each peptide ligand. To omit a peptide, set to a non-numeric value (e.g. "A"). Values in this column must be unique.
Peptide:* The peptide ligand sequence.
CloneFrequency: Applies only to phage display data: the observed frequency of the peptide in the cloning step.
QuantData: A number that relatively or absolutely quantifies the protein-ligand interaction. E.g. The optical density (OD) from a protein chip experiment.
ExternalIdentifier: A database identifier for the peptide.
To open several peptide files at once, simply link them all in a single project file. A project file is a text file containing the absolute paths of multiple peptide files. Opening the project file in LOLA will open each of the underlying peptide files in a single step, allowing logos to be constructed for multiple profiles.
#ProjectFile /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/APBA3-1.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/CASK-1.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/DLG1-1.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/DLG1-2.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/DLG1-3.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/DLG2-3.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/DLG3-2.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/DLG4-3.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/DVL2-1.pep.txt /Users/moyez/research/ppi/profiles/PDZ/Human/SidhuPhage/ERBB2IP-1-hi.pep.txt
NOTE: The first line of the project file must contain the text "#ProjectFile".
BRAIN Library 1.1 (2007 July 26)
- Added PDZ symbol style for PDZ type residue colouring in sequence logo generation code (required by LoLA tool)
1.0.6 (2007 June 12)
brain.jar: Ability to retrieve additional database references from ProteinProfile object (previously was only able to retrieve the first ID in the Accession field of the peptide file).
1.0.5 (2007 May 23)
- Code reorganization: brainPlugin.jar now holds only those classes related to the Cytoscape plugin. All other code has been moved to a new Brain Library project.
1.0.4 (2007 May 15)
- Network node can represent a single domain or a protein containing multiple domain instances (via new Advanced Options tab)
- Lower scoring motif hits are now reported
New node attribute Domain Name to hold a semantic domain identifier (Gene Name + Domain Number, for now)
1.0.3 (2007 April 23)
- Support for new peptide file format version 1.1 (and back-compatible with format version 1.0)
New node attributes Sequence Start, Sequence Stop, Comment for profiles generated from new peptide file format
1.0.2 (2007 April 11)
- Report SNPs for entire protein sequence and for domain subsequence only.
- Option to specify codon bias file
- Option to load unique peptides only from peptide file(s)
1.0.1 (2007 February 21)
- Port to Cytoscape API 2.4 and Java SE 5.0
If you have any questions or feedback, please email Moyez Dharsee at email@example.com.