The Innate Immune Database (IIDB).
BACKGROUND
As part of a National Institute of Allergy and Infectious Diseases funded collaborative project, we have performed over 150 microarray experiments measuring the response of C57/BL6 mouse bone marrow macrophages to toll-like receptor stimuli. These microarray expression profiles are available freely from our project web site http://www.innateImmunity-systemsbiology.org. Here, we report the development of a database of computationally predicted transcription factor binding sites and related genomic features for a set of over 2000 murine immune genes of interest. Our database, which includes microarray co-expression clusters and a host of web-based query, analysis and visualization facilities, is available freely via the internet. It provides a broad resource to the research community, and a stepping stone towards the delineation of the network of transcriptional regulatory interactions underlying the integrated response of macrophages to pathogens.


METHODS
We constructed a database indexed on genes and annotations of the immediate surrounding genomic regions. To facilitate both gene-specific and systems biology oriented research, our database provides the means to analyze individual genes or an entire genomic locus. Although our focus to-date has been on mammalian toll-like receptor signaling pathways, our database structure is not limited to this subject, and is intended to be broadly applicable to immunology. By focusing on selected immune-active genes, we were able to perform computationally intensive expression and sequence analyses that would currently be prohibitive if applied to the entire genome. Using six complementary computational algorithms and methodologies, we identified transcription factor binding sites based on the Position Weight Matrices available in TRANSFAC. For one example transcription factor (ATF3) for which experimental data is available, over 50% of our predicted binding sites coincide with genome-wide chromatin immnuopreciptation (ChIP-chip) results. Our database can be interrogated via a web interface. Genomic annotations and binding site predictions can be automatically viewed with a customized version of the Argo genome browser.


CONCLUSIONS
We present the Innate Immune Database (IIDB) as a community resource for immunologists interested in gene regulatory systems underlying innate responses to pathogens. The database website can be freely accessed at http://db.systemsbiology.net/IIDB.
Korb
Martin
M
Institute for Systems Biology, 1441 North 34thStreet, Seattle, Washington 98103-8904, USA. mkorb@systemsbiology.org
Rust
Aistair G
AG
Thorsson
Vesteinn
V
Battail
Christophe
C
Li
Bin
B
Hwang
Daehee
D
Kennedy
Kathleen A
KA
Roach
Jared C
JC
Rosenberger
Carrie M
CM
Gilchrist
Mark
M
Zak
Daniel
D
Johnson
Carrie
C
Marzolf
Bruz
B
Aderem
Alan
A
Shmulevich
Ilya
I
Bolouri
Hamid
H
D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D016000:Cluster Analysis; D017124:Conserved Sequence; D030541:Databases, Genetic; D016678:Genome; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D020407:Internet; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D012984:Software; D014157:Transcription Factors / Q000378:metabolism; D014584:User-Computer Interface
D014157:Transcription Factors