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:
(Note that only the InnateDB Innate Immunity Gene list is specific to innate immunity - other lists contain genes of relevance to immunity in general)

InnateDB Innate Immunity Genes (updated weekly)
Aside from annotating innate immunity interactions and pathways, the InnateDB curation team has also established a project to annotate genes that have a role in the innate immune response. This has been initiated in response to the fact that Gene Ontology annotation of the innate immune response is quite limited in the numbers of genes which have been identified and in response to the fact that many users have been eager to have a defined list of innate immune genes. For innate immune gene annotation, curators employ a new tool in the InnateDB curation system to associate relevant genes with publications which provide evidence for that gene having a role in innate immunity. Along with the link to the relevant publication(s), the curators provide a one-line summary of the role similar to Entrez GeneRIFs. Such genes are also automatically associated with the Gene Ontology term "innate immune response" in InnateDB, which provides a more comprehensive list of these genes for use in the InnateDB Gene Ontology over-representation analysis tool. To date, almost 800 genes have been annotated to some extent (as this is an on-going process). It should be noted that it is not the intention of InnateDB to comprehensively annotate all the roles of a given gene, but rather to provide a brief indication if a gene has a role in innate immunity.

This list provides details of over 900 genes which have been annotated by either InnateDB or Gene Ontology as having a role in the innate immune response.

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 5,889 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.
InnateDB currently contains 5,320 genes from this list (February 17, 2011).

ImmPort also provides links to the following lists:

Immunogenetic Related Information Source (IRIS)
This gene list, of 1,939 immune genes (February 17, 2011), is derived from the IRIS online database of known human defense genes (note that the IRIS database does not seem to be available anymore).
These genes were curated by IRIS 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 Septic Shock group which is a collaboration between ISB, TSRI and Rockefeller University research groups.
The list includes 1,426 genes with potential relevance to macrophage response to microbial stimulation (February 17, 2011). 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). It contains 820 genes (February 17, 2011); 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. A total of 3,714 unique 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.
InnateDB currently contains 3,480 genes from this study (February 17, 2011).

Immunome Database
Immunology-related genes were collected from research articles, textbooks and electronic information sources. The list contains genes that are directly 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, 1,059 genes were selected for InnateDB (February 17, 2011).

Other Interaction Databases


External Interaction Databases Integrated within InnateDB
Over 150,000 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).
(Please note that the numbers below may contain duplicates in case of interactions between human and murine genes or gene products.)

IntAct
Developed by the European Bioinformatics Institute, IntAct is a source of over 247,000 binary interactions that may be searched, visualized and downloaded.
InnateDB currently contains 34,131 human and 4,894 mouse interactions from IntAct (March 6, 2011).

Database of Interacting Proteins (DIP)
Source of over 70,000 binary interactions from organisms including mouse, rat, human, fruit fly and yeast.
InnateDB currently contains 3,566 human and 2,410 mouse interactions from DIP (March 6, 2011).

Molecular Interaction Database (MINT)
Contains more than 90,000 curated interactions - including more than 23,000 mammalian protein-protein interactions.
InnateDB currently contains 20,201 human and 2,989 mouse interactions from MINT (March 6, 2011).

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.
InnateDB currently contains 11,601 human and 2,886 mouse interactions from BIND (March 6, 2011).

BioGRID
Contains more than 370,000 curated interactions from organisms including Homo sapiens, Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans.
InnateDB currently contains 56,825 human and 2,263 mouse interactions from BioGRID (March 6, 2011).

Other Pathway Databases



External Pathway Databases Integrated within InnateDB
Cross references to 3,541 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 over 130,000 molecular interaction and reaction networks for metabolism, various cellular processes, and human diseases.
InnateDB currently contains 225 human and 222 mouse pathways from KEGG (March 6, 2011).

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 over 440 signaling pathways. It is a collaborative project between the US National Cancer Institute (NCI) and Nature Publishing Group (NPG).
InnateDB currently contains 430 human pathways from PID (March 6, 2011).

Integrating Network Objects with Hierarchies (INOH) Pathway Database
INOH is a pathway database providing 755 pathways from 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.
InnateDB currently contains 501 human and 245 mouse pathways from INOH (March 6, 2011).

NetPath
NetPath is a curated resource of 25 signal transduction pathways in humans. It is a collaboration between the Pandey Lab at Johns Hopkins University and the Institute of Bioinformatics, India.
InnateDB currently contains 20 human pathways from NetPath (March 6, 2011).

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. Reactome provides data for over 13,000 pathways.
InnateDB currently contains 998 human and 898 mouse pathways from Reactome (March 6, 2011).

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.
Please note that the IRIS database does not seem to be available anymore.

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.

Macrophages.com
Macrophages.com is an online resource for those interested in macrophages and their role as major effector cells in innate and adaptive immunity. This website is designed to act as a centralised resource for the worldwide community of scientists interested in different aspects of macrophage biology.

DC ATLAS project
DC-ATLAS is an immunological and bioinformatics integrated project, developed as a joint effort within the DC-THERA European Network of Excellence (www.dc-thera.org), a collaborating network established under the European Commission’s Sixth Framework Programme to translates discoveries from DC immunobiology into clinical therapies. The major scientific and technological goal of DC-ATLAS is to generate complete maps of the intracellular signaling pathways and regulatory networks that govern DC maturation/activation and function.

Immunological Genome Project (ImmGen)
The Immunological Genome Project is a collaborative group of Immunologists and Computational Biologists who are generating, under carefully standardized conditions, a complete microarray dissection of gene expression and its regulation in the immune system of the mouse. The project encompasses the innate and adaptive immune systems, surveying all cell types of the myeloid and lymphoid lineages with a focus on primary cells directly ex vivo.