Software


Freely available software used in and developed by members of the PI2 project includes:

Cerebral
CEREBRAL (CEll REgion-Based Rendering And Layout) is a Java plugin for the open-source and widely used Cytoscape molecular interaction viewer

Ortholuge
Ortholuge is a computational method that use a phylogenetic distance approach to evaluate ortholog predictions for two species compared to a third outgroup species.
ArrayPipe
ArrayPipe is a multi-functional microarray analysis pipeline.

ProbeLynx
ProbeLynx is a web-based tool for annotation of microarray data with up-to-date annotations.

Gene Lists


Lists of genes specific to immunity and curated by other research groups include:

InnateDB non-redundant list (Curated)
A non-redundant list of 5070 immune genes derived from Immport, IRIS, Septic Shock Group, MAPK/NFKB Network and Immunome Database. Only includes genes derived from curated immune gene lists.

InnateDB non-redundant list (Curated + Gene expression)
A non-redundant list 7497 immune genes derived from Immport, IRIS, Septic Shock Group, MAPK/NFKB Network, Inflammasome and Immunome Database. Includes genes derived from both curated immune gene lists and gene expression data.
Immport
The Immunology Database and Analysis Portal (ImmPort) system was developed under the Bioinformatics Integration Support Contract (BISC) Phase II by the Northrop Grumman Information Technology Health Solutions team for the NIH, NIAID, and DAIT. The principal investigator of the BISC project is Dr. Richard Scheuermann at University of Texas Southwestern Medical Center. The list of immunologically related genes in ImmPort is a collection of 4055 human genes, which was formed with the goal of retrieving all genes that have immune system-related functions. This list was generated using automatic searches of EntrezGene and Gene Ontology records using immunology-related keywords. The list was then manually curated by immunology experts examining various literature sources.

ImmPort also provides links to the following lists:

IRIS
This gene list is derived from the IRIS (Immunogenetic Related Information Source) online database of known human defense genes. A list of 1562 immune genes were curated from the literature where an immune gene was defined as a complete gene that produces a functional transcript and demonstrates at least one of the following defense characteristics: (i) Known or putative function in innate or adaptive immunity, (ii) Participates in the development or maturation of immune system components (iii) Induced by immunomodulators, (iv) Encodes a protein expressed primarily in immune tissues, (v) Participates in an immune pathway that results in the expression of defense molecules, (vi) Produces a protein that interacts directly with pathogens or their products.

Septic Shock Group
This gene list is derived from the www.septicshock.org group which is a collaboration between ISB, TSRI and Rockefeller University research groups. The list includes 1580 genes with potential relevance to macrophage response to microbial stimulation. The list combines genes with significant expression changes under stimulation with LPS, and genes coding for proteins known to interact in the TNFa/NF-kB signaling pathway.

MAPK/NFKB Network
This gene list was derived from in house curation of the p38, ERK, JNK signaling pathways (Raymond Lo and Fiona Roche) and the NFKB transcriptional regulatory module (Jenn Gardy). Members of the TNF-alpha and IFN-alpha signaling pathway derived from Transpath data were also included.

Calvano et al., Nature 2005
This study used microarrays to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus (bacterial endotoxin). Here they evaluate the genome-wide response to systemic inflammation in the context of a fully predictable recovery. Gene expression in whole blood leukocytes was determined immediately before and at 2, 4, 6, 9 and 24 h after the intravenous administration of bacterial endotoxin to four healthy human subjects. Four additional subjects were studied under identical conditions but without endotoxin administration. Genes that were significantly perturbed after bacterial endotoxin administration were identified using significance analysis of microarrays (SAM) (multiclass response), with an estimated false discovery rate of <0.1% on the basis of 1,000 permutations. Genes showing significant transcriptional changes were verified in another microarray study where an additional six healthy subjects (one female and five males) were administered 2 ng kg-1 (body weight) endotoxin, and blood samples were collected before (0 h) and after (2 and 6 h) endotoxin infusion

Immunome Database
Immunology-related genes were collected from research articles, textbooks and electronic information sources. The list contains genes that aredirectly involved in immunological processes. In addition to clearly defined groups, such as clusters of differentiation (CD) molecules, chemokines and their receptors, other essential genes were included. Genes were included when they are undoubtedly needed for immunity. Immunodeficiency-related genes were taken from the ImmunoDeficiency Resource and IDbases. Proteins that are expressed in nearly all cells were excluded, although their functions may also be needed in immunity related cells and tissues. Only full-length genes were included; thus, the gene segments of immunoglobulins, B and T cell receptors and major histocompatibility complexes (MHCs) were excluded. In the case of signaling molecules, only those involved in immunity-related cascades were included. Altogether, 847 genes were selected for the database.

Other Interaction Databases


External Interaction Databases Integrated within InnateDB
More than 100,000 interactions have been integrated into InnateDB from the Molecular Interaction database (MINT) (Chatr-aryamontri et al, 2007); the IntAct database (Kerrien et al, 2007); the Database of Interacting Proteins (DIP) (Salwinski et al, 2004); the General Repository for Interaction Datasets (BioGRID) (Breitkreutz et al, 2007) and the Biomolecular Interaction Network Database (BIND) (Alfarano et al, 2005).

IntAct
Developed by the European Bioinformatics Institute, IntAct is a source of over 150,000 binary interactions that may be searched, visualized and downloaded.

Database of Interacting Proteins (DIP)
Source of over 50,000 binary interactions from organisms including mouse, rat, human, fruit fly and yeast.

Molecular Interaction Database (MINT)
Contains more than 100,000 curated interactions - including more than 23,000 mammalian protein-protein interactions.

Biomolecular Interaction Network Database (BIND)
Now integrated with the Biomolecular Object Network Databank (BOND) since being acquired by Unleashed Informatics, BIND is a source of curated interaction, reaction, complex and pathway information.

BioGRID
Contains more than 130,000 curated interactions from organisms including Homo sapiens, Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans.

Other Pathway Databases



External Pathway Databases Integrated within InnateDB
Cross references to more than 2,000 human and mouse pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database (Kanehisa et al, 2007), the NCI-Nature Pathway Interaction Database (PID) (http://pid.nci.nih.gov), Integrating Network Objects with Hierarchies (INOH) pathway database (http://www.inoh.org/), NetPath (http://www.netpath.org) and the Reactome database (Joshi-Tope et al, 2005) have also been integrated into InnateDB.

KEGG
Contains molecular interaction and reaction networks for metabolism, various cellular processes, and human diseases.

NCI-Nature Pathway Interaction Database (PID)
The Pathway Interaction Database is a highly structured, curated collection of information about known biomolecular interactions and key cellular processes assembled into signaling pathways. It is a collaborative project between the US National Cancer Institute (NCI) and Nature Publishing Group (NPG).

Integrating Network Objects with Hierarchies (INOH) Pathway Database
INOH is a pathway database of model organisms including human, mouse, rat and others. In INOH, the term pathway refers to higher order functional knowledge such as relationships among multiple bio-molecules that constitute signal transduction pathways or biological events in general.

NetPath
NetPath is a curated resource of signal transduction pathways in humans. It is a collaboration between the Pandey Lab at Johns Hopkins University and the Institute of Bioinformatics, India.

Reactome
The Reactome project is a collaboration among Cold Spring Harbor Laboratory, The European Bioinformatics Institute, and The Gene Ontology Consortium to develop a curated resource of core pathways and reactions in human biology.

Immunology Relevant Databases



The following external databases contain immunology-relevant data.
Reference Database of Immune Cells (RefDIC)
RefDIC is an open resource of quantitative mRNA/Protein profile data specifically for immune cells. Various aspects of mRNA/Protein profiles of immune cells can be retrieved from RefDIC.

Innate Immune Database (IIDB)
IIDB is a repository of computationally-predicted transcription factor binding sites for over 2000 mouse genes associated with immune response behavior. A specific focus of IIDB is on Toll-like Receptor (TLR) genes, which are key components of innate immunity

Immunology Database and Analysis Portal (ImmPort)
The ImmPort system provides information technology support in the production, analysis, archiving, and exchange of scientific data for researchers supported by NIAID/DAIT. It serves as a long-term, sustainable archive of data generated by investigators funded through the NIAID/DAIT. The ImmPort system also provides data analysis tools and an immunology-focused ontology.

Immunogenetic Related Information Source (IRIS)
IRIS is a database of all known human defence genes, produced in the laboratory of Professor John Trowsdale at the University of Cambridge. IRIS currently includes chromosomal locations, functional annotations, and sequence data for over 1,500 functional human immune genes.

Immunome Database for Genes and Proteins of the Human Immune System
Immumome contains information about immune-related proteins, their domain structure and related ontology terms. Information can also be found for the localization of the coding genes and their comparison with the existing mouse orthologs.