Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/388
Título: Model Checking to Assess T-Helper Cell Plasticity
Autor: Abou-Jaoudé, Wassim
Monteiro, Pedro T.
Naldi, Aurélien
Grandclaudon, Maximilien
Soumelis, Vassili
Chaouiya, Claudine
Thieffry, Denis
Palavras-chave: logical modeling
signaling networks
T-helper lymphocyte
cell differentiation
cell plasticity
model checking
Data: 28-Jan-2015
Editora: Frontiers Research Foundation
Citação: Abou-Jaoudé W, Monteiro PT, Naldi A, Grandclaudon M, Soumelis V, Chaouiya C and Thieffry D (2015) Model checking to assess T-helper cell plasticity. Front. Bioeng. Biotechnol. 2:86. doi: 10.3389/fbioe.2014.00086
Resumo: Computational modeling constitutes a crucial step toward the functional understanding of complex cellular networks. In particular, logical modeling has proven suitable for the dynamical analysis of large signaling and transcriptional regulatory networks. In this context, signaling input components are generally meant to convey external stimuli, or environmental cues. In response to such external signals, cells acquire specific gene expression patterns modeled in terms of attractors (e.g., stable states). The capacity for cells to alter or reprogram their differentiated states upon changes in environmental conditions is referred to as cell plasticity. In this article, we present a multivalued logical framework along with computational methods recently developed to efficiently analyze large models. We mainly focus on a symbolic model checking approach to investigate switches between attractors subsequent to changes of input conditions. As a case study, we consider the cellular network regulating the differentiation of T-helper (Th) cells, which orchestrate many physiological and pathological immune responses. To account for novel cellular subtypes, we present an extended version of a published model of Th cell differentiation. We then use symbolic model checking to analyze reachability properties between Th subtypes upon changes of environmental cues. This allows for the construction of a synthetic view of Th cell plasticity in terms of a graph connecting subtypes with arcs labeled by input conditions. Finally, we explore novel strategies enabling specific Th cell polarizing or reprograming events.
Peer review: yes
URI: http://hdl.handle.net/10400.7/388
DOI: 10.3389/fbioe.2014.00086
Versão do Editor: http://journal.frontiersin.org/article/10.3389/fbioe.2014.00086/abstract
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