Paper Info
Title
A computational analysis of dynamic, multi-organ inflammatory crosstalk induced by endotoxin in mice.
Abstract
Bacterial lipopolysaccharide (LPS) induces an acute inflammatory response across multiple organs, primarily via Toll-like receptor 4 (TLR4). We sought to define novel aspects of the complex spatiotemporal dynamics of LPS-induced inflammation using computational modeling, with a special focus on the timing of pathological systemic spillover. An analysis of principal drivers of LPS-induced inflammation in the heart, gut, lung, liver, spleen, and kidney to assess organ-specific dynamics, as well as in the plasma (as an assessment of systemic spillover), was carried out using data on 20 protein-level inflammatory mediators measured over 0-48h in both C57BL/6 and TLR4-null mice. Using a suite of computational techniques, including a time-interval variant of Principal Component Analysis, we confirm key roles for cytokines such as tumor necrosis factor-alpha and interleukin-17A, define a temporal hierarchy of organ-localized inflammation, and infer the point at which organ-localized inflammation spills over systemically. Thus, by employing a systems biology approach, we obtain a novel perspective on the time- and organ-specific components in the propagation of acute systemic inflammation.
Year
DOI
Venue
2018
10.1371/journal.pcbi.1006582
PLOS COMPUTATIONAL BIOLOGY
DocType
Volume
Issue
Journal
14
11
ISSN
Citations 
PageRank 
1553-734X
0
0.34
References 
Authors
0
11
Name
Order
Citations
PageRank
Ruben Zamora100.34
Sebastian Korff200.34
Qi Mi331.12
Derek Barclay400.34
Lukas Schimunek500.34
Riccardo Zucca67011.03
Xerxes D. Arsiwalla78417.84
Richard L Simmons800.34
Paul F. M. J. Verschure9677116.64
Timothy R Billiar1000.68
Yoram Vodovotz11184.76