Abstract：
:Oligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens. However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus (bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans.
journal_name
Naturejournal_title
Natureauthors
Calvano SE,Xiao W,Richards DR,Felciano RM,Baker HV,Cho RJ,Chen RO,Brownstein BH,Cobb JP,Tschoeke SK,Miller-Graziano C,Moldawer LL,Mindrinos MN,Davis RW,Tompkins RG,Lowry SF,Inflamm and Host Response to Injury Large Scaledoi
10.1038/nature03985keywords:
subject
Has Abstractpub_date
2005-10-13 00:00:00pages
1032-7issue
7061eissn
0028-0836issn
1476-4687pii
nature03985journal_volume
437pub_type
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