Oscillatory stimuli differentiate adapting circuit topologies. Rahi, S. J., Larsch, J., Pecani, K., Mansouri, N., Katsov, A. Y., Tsaneva-Atanasova, K., Sontag, E. D., & Cross, F. R. Nature Methods, 14:1010-1016, 2017.
abstract   bibtex   
Elucidating the structure of biological intracellular networks from experimental data remains a major challenge. This paper studies two types of ``response signatures'' to identify specific circuit motifs, from the observed response to periodic inputs. In particular, the objective is to distinguish negative feedback loops (NFLs) from incoherent feedforward loops (IFFLs), which are two types of circuits capable of producing exact adaptation. The theory of monotone systems with inputs is used to show that ``period skipping'' (non-harmonic responses) is ruled out in IFFL's, and a notion called ``refractory period stabilization'' is also analyzed. The approach is then applied to identify a circuit dominating cell cycle timing in yeast, and to uncover a calcium-mediated NFL circuit in \emphC.elegans olfactory sensory neurons.
@ARTICLE{rahi2017,
   AUTHOR       = {S. J. Rahi and J. Larsch and K. Pecani and N. Mansouri and 
      A. Y. Katsov and K. Tsaneva-Atanasova and E. D. Sontag and 
      F. R. Cross},
   JOURNAL      = {Nature Methods},
   TITLE        = {Oscillatory stimuli differentiate adapting circuit 
      topologies},
   YEAR         = {2017},
   OPTMONTH     = {},
   OPTNOTE      = {},
   OPTNUMBER    = {},
   PAGES        = {1010-1016},
   VOLUME       = {14},
   KEYWORDS     = {biochemical networks, periodic behaviors, 
      monotone systems, entrainment, oscillations},
   PDF          = {../../FTPDIR/rahi_et_al_nature_methods_2017_reprint.pdf},
   ABSTRACT     = {Elucidating the structure of biological intracellular 
      networks from experimental data remains a major challenge. This paper 
      studies two types of ``response signatures'' to identify specific 
      circuit motifs, from the observed response to periodic inputs. In 
      particular, the objective is to distinguish negative feedback loops 
      (NFLs) from incoherent feedforward loops (IFFLs), which are two types 
      of circuits capable of producing exact adaptation. The theory of 
      monotone systems with inputs is used to show that ``period skipping'' 
      (non-harmonic responses) is ruled out in IFFL's, and a notion called 
      ``refractory period stabilization'' is also analyzed. The approach is 
      then applied to identify a circuit dominating cell cycle timing in 
      yeast, and to uncover a calcium-mediated NFL circuit in 
      \emph{C.elegans} olfactory sensory neurons.}
}

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