Model checking to assess T-helper cell plasticity

Frontiers in Bioengineering and Biotechnology

Aurélien eNaldi¹  Denis eThieffry³  Maximilien eGrandclaudon⁴  Vassili eSoumelis⁴  Pedro T Monteiro⁶  Claudine eChaouiya⁶  Wassim eAbou-Jaoudé⁸ 

[1] Centre Intégratif de Génomique, Université de Lausanne;INESC-ID;INSERM U1024;INSERM U932;Institut de Biologie de l’École Normale Supérieure;Instituto Gulbenkian de Ciência;Laboratoire d’Immunologie Clinique - Institut Curie;Laboratoire d’Informatique de l’École Normale Supérieure,;UMR CNRS 8197;

关键词: Cell Differentiation;    model checking;    signaling networks;    Logical modeling;    Cell plasticity;    T-helper lymphocyte;   

DOI  :  10.3389/fbioe.2014.00086

来源: DOAJ

【 摘 要 】

Computational modeling constitutes a crucial step towards 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 ({em 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 largemodels.We mainly focus on a symbolic model checking approach to investigate switches between attractors subsequent to changes ofinput conditions.As a case study, we consider the cellular network regulating the differentiation of T-helper cells, which orchestrate many physiological and pathological immune responses.To account for novel cellular subtypes, we present an extended version of a publishedmodel of T-helper cell differentiation. We then use symbolic model checking to analyze reachability properties between T-helper subtypes upon changes of environmental cues.This allows for the construction of a synthetic view of T-helper cell plasticity in terms of a graph connecting subtypes with arcs labeled by input conditions.Finally, we explore novel strategies enabling specific T-helper cell polarizing or reprograming events.

【 授权许可】

Unknown