title: From top-down to bottom-up: computational modeling approaches for cellular redoxin networks.
abstract: CONCLUSIONS
  Thioredoxin, glutaredoxin, and peroxiredoxin systems play critical roles in a large number of redox-sensitive cellular processes. These systems are linked to each other by coupled redox cycles and common reaction intermediates into a larger network. Given the scale and connectivity of this network, computational approaches are required to analyze its dynamics and organization.
  
  
  BACKGROUND
  Theoretical advances, as well as new redox proteomic methods, have led to the development of both top-down and bottom-up systems biology approaches to analyze the these systems and the network as a whole. Top-down approaches have been based on modifications to the Nernst equation or on graph theoretical approaches, while bottom-up approaches have been based on kinetic or stoichiometric modeling techniques.
  
  
  RESULTS
  This review will consider the rationale behind these approaches and focus on their advantages and limitations. Further, the review will discuss modeling standards to ensure model accuracy and availability.
  
  
  CONCLUSIONS
  Top-down and bottom-up approaches have distinct strengths and limitations in describing cellular redoxin networks. The availability of methods to overcome these limitations, together with the adoption of common modeling standards, is expected to increase the pace of model-led discovery within the redox biology field.
authors.affiliation: School of Life Sciences, University of Kwa-Zulu Natal, Scottsville, South Africa. pillayc3@ukzn.ac.za
authors.forename: Ché S
authors.initials: CS
authors.lastname: Pillay
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Hofmeyr
authors.forename: Lefentse N
authors.initials: LN
authors.lastname: Mashamaite
authors.forename: Johann M
authors.initials: JM
authors.lastname: Rohwer
mesh_terms: D003198:Computer Simulation; D054477:Glutaredoxins / Q000378:metabolism*; D006801:Humans; D054464:Peroxiredoxins / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D054477:Glutaredoxins; D013438:Sulfhydryl Compounds; D013879:Thioredoxins; D054464:Peroxiredoxins