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Simulation of the dynamics of primary immunodeficiencies in CD4+ T-cells

Teku, Gabriel N. LU and Vihinen, Mauno LU (2017) In PLoS ONE 12(4).
Abstract

Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-Tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes. The results for several... (More)

Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-Tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes. The results for several loss-of-function PID simulations correspond to results of previously reported molecular studies. The simulations for TCR PTPRC, LCK, ZAP70 and ITK indicate profound changes to numerous proteins in the network. Significant effects were observed also in the BCL10, CARD11, MALT1, NEMO, IKKB and MAP3K14 simulations. No major effects were observed for PIDs that are caused by constitutively active proteins. The T-cell model facilitates the understanding of the underlying dynamics of PID disease processes. The approach confirms previous knowledge about T-cell signaling network and indicates several new important proteins that may be of interest when developing novel diagnosis and therapies to treat immunological defects.

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publication status
published
subject
in
PLoS ONE
volume
12
issue
4
publisher
Public Library of Science
external identifiers
  • scopus:85018269941
  • wos:000400383600090
ISSN
1932-6203
DOI
10.1371/journal.pone.0176500
language
English
LU publication?
yes
id
af22ddd4-262e-4744-8ff8-22c143158277
date added to LUP
2017-06-01 13:56:56
date last changed
2018-01-07 12:06:01
@article{af22ddd4-262e-4744-8ff8-22c143158277,
  abstract     = {<p>Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-Tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes. The results for several loss-of-function PID simulations correspond to results of previously reported molecular studies. The simulations for TCR PTPRC, LCK, ZAP70 and ITK indicate profound changes to numerous proteins in the network. Significant effects were observed also in the BCL10, CARD11, MALT1, NEMO, IKKB and MAP3K14 simulations. No major effects were observed for PIDs that are caused by constitutively active proteins. The T-cell model facilitates the understanding of the underlying dynamics of PID disease processes. The approach confirms previous knowledge about T-cell signaling network and indicates several new important proteins that may be of interest when developing novel diagnosis and therapies to treat immunological defects.</p>},
  articleno    = {0176500},
  author       = {Teku, Gabriel N. and Vihinen, Mauno},
  issn         = {1932-6203},
  language     = {eng},
  month        = {04},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Simulation of the dynamics of primary immunodeficiencies in CD4+ T-cells},
  url          = {http://dx.doi.org/10.1371/journal.pone.0176500},
  volume       = {12},
  year         = {2017},
}