Supplementary Figures and Tables to:

Potential landscapes, bifurcations and robustness of tristable networks

Anupam Dey and Debashis Barik*

School of Chemistry, University of Hyderabad, Central University P.O., Hyderabad, 500046,

Telangana, India

*Corresponding author, E-mail: dbariksc@uohyd.ac.in

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Supporting Information

Table of Contents

S1 Figure: Steady state population distributions of B overlaid on top of contours of potential and 1-p
bifurcation diagram in the DNFL-B.
S2 Figure: Steady state joint population distributions of the dynamical variable A and B for the four
types of tristable switches in the DNFL-B network.
S3 Figure: 1-p bifurcation diagrams overlaid on top of contours of potential for the model DNFL-B.
S4 Figure: 1-p bifurcation diagrams overlaid on top of contours of potential for the model DNFL-A.
S5 Figure: Classification of 3-C networks into MIMI, MIMA and MAMA categories.
S6 Figure: Average percentages for four types of tristabilities in the 2-and 3-C motifs.
S7 Figure: The four types of 1-p bifurcation diagrams from EMT-B2 network.
S8 Figure: Dual-bistable bifurcation diagrams from the EMT-B2 network.
S9 Figure: Robustness of the DNFL-BnA and DNFL-BpA networks.
S10 Figure: Comparison of tristability from the unperturbed network and bistability from the
perturbed network.
S11 Figure: The local parameter sensitivity of the 2-C networks.
S12 Figure: Distributions of Hill coefficients in 2- and 3-C motifs.
S13 Figure: Distributions of Hill coefficients in SATS motifs.
S14 Figure: Effect of Hill coefficient on the tristability and the robustness of tristable response.
S15 Figure: Steady state distributions of A and B in the DNFL-B motif with random input signal S.
S16 Figure: Steady state distributions of A and B in the DNFL-A motif with random input signal S.
S17 Figure: Comparison of potential-based and integration-based (RACIPE method) methods.
S1 Table: The dynamical equations and the ranges of parameter values for all the networks
investigated.
S2 Table: The parameter values corresponding to four types of tristable bifurcations for the DNFL-B
network.
S3 Table: Examples of networks consisting of self-activation mutual inhibition motif.
MATLAB codes

2
S1 Figure: Steady state population distributions for the four types of tristabilities in the DNFL-B
network are plotted together with the contours of the potential energy and 1-p bifurcation diagrams.
The distributions were obtained from stochastic simulations of the model using Gillespie’s stochastic
simulation algorithm. At each S an ensemble of 10000 simulations were run with random initial values
between 0 and 1000. The intensity of the color indicates the density of the population. Low and high
density are represented by yellow and green, respectively.

3
S2 Figure: Steady state joint population distributions of the dynamical variable A and B for the four
types of tristable switches in the DNFL-B network. The distributions were obtained from the stochastic
simulations of the model.

4
S3 Figure: The 1-p bifurcation diagrams generated by the potential landscape based method are
overlaid on top of the contours of the logarithm of the energy (ln(𝑉(𝑆, 𝐵))) for the DNFL-B network.
The black and red lines represent the stable and unstable branches, respectively.

5
S4 Figure: The 1-p bifurcation diagrams generated by the potential landscape based method are
overlaid on top of the contours of the logarithm of the energy (ln(𝑉(𝑆, 𝐴))) for the DNFL-A network.
The black and red lines represent the stable and unstable branches, respectively.

6
S5 Figure: Classification of the 3-component network motifs based on the type of interactions each
node has with the neighbouring node. Note that DNFL-Ap2 and PFL-An2 are the equivalent networks.

7
S6 Figure: Average percentage of four types of tristable bifurcations for the networks in the
2-and 3-C motifs. The networks with low average total TS count are not included to avoid large noise.

8
S7 Figure: The four types of 1-p bifurcation diagrams from EMT-B2 network. The bifurcation
diagrams are overlaid on top of contours of the logarithm of the effective potential energy
(ln(𝑉(𝑆, 𝐵))). The arrows indicate the ON and OFF signalling thresholds. The number of ON and OFF
thresholds for each type are; Type I: Two ON and two OFF; Type II: One ON and two OFF; Type III:
Two ON and one OFF; Type IV: One ON and one OFF. The black and red lines represent the stable
and unstable steady states, respectively.

9
S8 Figure: Dual-bistable bifurcation diagrams from the EMT-B2 network. In each subplot we have
plotted five dual-bistable bifurcation diagrams that were constructed from the potential landscape of
the model under random parameter variations. In total we have plotted 125 such bifurcations.

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S9 Figure: a) The DNFL-BnA and DNFL-BpA networks where B inhibits and activates A via C,
respectively. b) The tristable count for these two networks for 500000 random parameter
combinations. The different colors indicate the four different types of tristable responses.

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S10 Figure: Comparison of tristability from the unperturbed network and bistability from the
perturbed network without the self-activation. In the comparison the parameter set was the same for
both cases.

12
S11 Figure: The local parameter sensitivity of the 2-C networks. The tristability count for the variation
of each parameter (sample space of 10000) for the four networks. We performed local parameter
sensitivity analysis of all four 2-C motifs to understand the role of individual parameters in tristability.
We began with a parameter set that resulted in tristability, then we counted the number of times the
model generated tristable bifurcation diagrams when a particular parameter was varied keeping other
parameters fixed.

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S12 Figure: Plot of distribution of Hill coefficients for the tristable response in all the 2- and 3-C
networks. For a particular network each Hill coefficient is normalized to the total number of tristable
count.

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S13 Figure: Plot of the distribution of Hill coefficients for the tristable response in four SATS networks.
For a particular network each Hill coefficient is normalized to the total number of tristable count.

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S14 Figure: Effect of Hill coefficient on the tristability and the robustness of tristable response. We
performed bifurcation analysis of models by choosing a fixed value (=2) and a lower range (=1-4) of
the Hill coefficients in 2-C and 3-C motifs (top row) and EMT motifs (bottom row). The results are from
three independent runs each having a parameter space of 100,000 random combinations.

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S15 Figure: Plot of stable steady state distribution of A and B in the 2-C MISA-B (DNFL-B) motif with
random value of the input signal S for three different values of the Hill coefficient. In the first, second,
third and fourth column we plot the monostable SS, bistable SS, tristable SS and all SS together,
respectively. The number of SS are indicated inside each plot. The values of A and B were normalized
using 𝑋𝑛𝑜𝑟𝑚𝑎𝑙𝑖𝑧𝑒𝑑 = (log 2 𝑋 −< log 2 𝑋 >)/𝑆𝑡𝑑(log 2 𝑋). The plots are from a single run of parameter
space of 10,000.

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S16 Figure: Plot of stable steady state distribution of A and B in the 2-C MISA-A (DNFL-A) motif with
random value of the input signal S for three different values of the Hill coefficient. In the first, second,
third and fourth column we plot the monostable SS, bistable SS, tristable SS and all SS together,
respectively. The number of SS are indicated inside each plot. The values of A and B were normalized
using 𝑋𝑛𝑜𝑟𝑚𝑎𝑙𝑖𝑧𝑒𝑑 = (log 2 𝑋 −< log 2 𝑋 >)/𝑆𝑡𝑑(log 2 𝑋). The plots are from a single run of parameter
space of 10,000.

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S17 Figure: Comparison of potential-based and integration-based (RACIPE method 1) methods. a)
Comparison of counts of mono-stable, bistable and tristable steady states from the potential-based
and RACIPE method with different number of initial conditions for the DNFL-B network. In the ‘RACIPE-
X’, the ‘X’ represents the number of random initial values, distributed in the range 0-1500 for both the
variables, used in the numerical integrations. With the increasing number of initial conditions, the
overestimation of monostability decreases and subsequently counts for the bistability and tristability
increases in the RACIPE calculations. Note that potential based method is not dependent on the initial
𝑑𝐵 𝑑𝐴
conditions. b) The plot of phase planes (Red; = 0, Blue; = 0) and the trajectories from random
𝑑𝑡 𝑑𝑡
initial conditions. The stable and unstable steady states are shown in black and red filled circles,
respectively. The nullclines and the trajectories clearly indicate that one stable steady state possesses
a very small basin of attraction as compared to other two steady states. c-f) Correlation between
steady states from both the methods for different number of initial conditions in the RACIPE method.
The correlation is quite poor for low number of initial conditions in RACIPE and it improves with the
increase of number of random initial conditions. g) Comparison of computational cost between the
potential and RACIPE methods. The equations and the parameter ranges used are from the RACIPE
model 1.

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S1 Table: The dynamical equations and the ranges of parameter values for all the networks
investigated. Note that in all equations the signal, S, is multiplied a scaling factor (=100)

Network Topology Dynamical Equations Parameter Ranges

𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵, 𝐴) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝑔𝐵,0 + 𝑔𝐵,𝐴− . 𝐻2− (𝐴) − 𝑘𝐵 . 𝐵
𝑑𝑡 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆+ 𝐵− 𝐴−
𝐺𝐴 (𝑆, 𝐵, 𝐴)
= 𝑔𝐴,𝑆− 𝐵− 𝐴− . 𝐻− (𝑆). 𝐻 − (𝐵). 𝐻1− (𝐴) 𝑔𝐴,𝑆− 𝐵− 𝐴− > 𝑔𝐴,𝑆− 𝐵+ 𝐴−
+ 𝑔𝐴,𝑆+ 𝐵− 𝐴− . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻1− (𝐴)
+ 𝑔𝐴,𝑆− 𝐵+ 𝐴− . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻1− (𝐴) 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆− 𝐵− 𝐴+
+ 𝑔𝐴,𝑆− 𝐵− 𝐴+ . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻1+ (𝐴)
𝑔𝐴,𝑆− 𝐵− 𝐴− = 𝑔𝐴,𝑆+ 𝐵+ 𝐴−
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐴− . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻1− (𝐴)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐴+ . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻1+ (𝐴)
𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆+ 𝐵− 𝐴+
+ 𝑔𝐴,𝑆− 𝐵+ 𝐴+ . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻1+ (𝐴)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐴+ . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻1+ (𝐴)
𝑔𝐴,𝑆− 𝐵− 𝐴− = 𝑔𝐴,𝑆− 𝐵+ 𝐴+

1 𝑔𝐴,𝑆− 𝐵− 𝐴− = 𝑔𝐴,𝑆+ 𝐵+ 𝐴+
− (𝑆)
𝐻 =
𝑆 𝑛𝑆,𝐴
1+( ) 𝑔𝐵,0 < 𝑔𝐵,𝐴−
𝑆𝐴,0

𝐻 + (𝑆) = 1 − 𝐻 − (𝑆)
𝑔𝐴,𝑆− 𝐵− 𝐴− 1-10

1 𝑔𝐴,𝑆+ 𝐵− 𝐴− 10-50
𝐻 − (𝐵) =
𝐵 𝑛𝐵,𝐴 𝑔𝐴,𝑆− 𝐵+ 𝐴− 0.1-1
1+( )
𝐵𝐴,0
𝑔𝐴,𝑆− 𝐵− 𝐴+ 10-50
𝐻 + (𝐵) = 1 − 𝐻− (𝐵)
𝑔𝐴,𝑆+ 𝐵− 𝐴+ 10-50
1
𝐻1− (𝐴) = 𝑔𝐵,0 1-10
𝐴 𝑛𝐴,𝐴
1+( )
𝐴𝐴,0 𝑔𝐵,𝐴− 10-50
𝐻1+ (𝐴) = 1 − 𝐻1− (𝐴) 𝑘𝐴 , 𝑘𝐵 0.01-0.1
𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1-6
1 𝑛𝐴,𝐴
𝐻2− (𝐴) = From
𝐴 𝑛𝐴,𝐵
1+( ) 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐴𝐵,0
𝐴𝐴,0 functional
𝐻2+ (𝐴) = 1 − 𝐻2− (𝐴) rule

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Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝐴, 𝐵) − 𝑘𝐵 . 𝐵
𝑑𝑡

𝐺𝐴 (𝑆, 𝐵)
= 𝑔𝐴,𝑆− 𝐵− . 𝐻 − (𝑆). 𝐻1− (𝐵) 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵−
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻 + (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻 − (𝑆). 𝐻1+ (𝐵) 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆− 𝐵+
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻 + (𝑆). 𝐻1+ (𝐵)
𝑔𝐴,𝑆− 𝐵− = 𝑔𝐴,𝑆+ 𝐵+
𝐺𝐵 (𝐴, 𝐵)
= 𝑔𝐵,𝐴− 𝐵− . 𝐻 − (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝐴− 𝐵− > 𝑔𝐵,𝐴+ 𝐵−
+ 𝑔𝐵,𝐴+ 𝐵− . 𝐻 + (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝐴− 𝐵+ . 𝐻 − (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝐴− 𝐵− < 𝑔𝐵,𝐴− 𝐵+
+ 𝑔𝐵,𝐴+ 𝐵+ . 𝐻 + (𝐴). 𝐻2+ (𝐵)
𝑔𝐵,𝐴− 𝐵− = 𝑔𝐵,𝐴+ 𝐵+
1
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴 𝑔𝐴,𝑆− 𝐵− 1-10
1+( )
𝑆𝐴,0
𝑔𝐴,𝑆+ 𝐵− 10-50
𝐻 + (𝑆) = 1 − 𝐻 − (𝑆)
𝑔𝐴,𝑆− 𝐵+ 0.1-1

𝑔𝐵,𝐴− 𝐵− 1-10
1
𝐻1− (𝐵) =
𝐵 𝑛𝐵,𝐴 𝑔𝐵,𝐴+ 𝐵− 0.1-1
1+( )
𝐵𝐴,0
𝑔𝐵,𝐴− 𝐵+ 10-50
𝐻1+ (𝐵) =1− 𝐻1− (𝐵)
𝑘𝐴 , 𝑘𝐵 0.01-0.1
1 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
𝐻 − (𝐴) = 1-6
𝐴 𝑛𝐴,𝐵 𝑛𝐵,𝐵
1+( )
𝐴𝐵,0 From
𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐻 + (𝐴) = 1 − 𝐻 − (𝐴) 𝐵𝐵,0 functional
rule

1
𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐵
1+( )
𝐵𝐵,0

𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵)

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Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵, 𝐴) − 𝑘𝐴 . 𝐴
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆+ 𝐵− 𝐴−
𝑑𝐵
= 𝑔𝐵,0 + 𝑔𝐵,𝐴+ . 𝐻2+ (𝐴) − 𝑘𝐵 . 𝐵
𝑑𝑡 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆− 𝐵+ 𝐴−

𝐺𝐴 (𝑆, 𝐵, 𝐴) 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆− 𝐵− 𝐴+

= 𝑔𝐴,𝑆− 𝐵− 𝐴− . 𝐻− (𝑆). 𝐻 − (𝐵). 𝐻1− (𝐴)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐴− . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻1− (𝐴) 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆+ 𝐵+ 𝐴−
+ 𝑔𝐴,𝑆− 𝐵+ 𝐴− . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻1− (𝐴)
+ 𝑔𝐴,𝑆− 𝐵− 𝐴+ . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻1+ (𝐴) 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆+ 𝐵− 𝐴+
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐴− . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻1− (𝐴)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐴+ . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻1+ (𝐴) 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆− 𝐵+ 𝐴+
+ 𝑔𝐴,𝑆− 𝐵+ 𝐴+ . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻1+ (𝐴)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐴+ . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻1+ (𝐴) 𝑔𝐴,𝑆− 𝐵− 𝐴− < 𝑔𝐴,𝑆+ 𝐵+ 𝐴+

𝑔𝐵,0 < 𝑔𝐵,𝐴+

1
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0 𝑔𝐴,𝑆− 𝐵− 𝐴− 1-10
𝐻 + (𝑆) = 1 − 𝐻 − (𝑆) 𝑔𝐴,𝑆+ 𝐵− 𝐴− 10-50

𝑔𝐴,𝑆− 𝐵+ 𝐴− 10-50
1
𝐻 − (𝐵) = 𝑔𝐴,𝑆− 𝐵− 𝐴+ 10-50
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐴,𝑆+ 𝐵+ 𝐴− 10-50

𝐻 + (𝐵) = 1 − 𝐻− (𝐵) 𝑔𝐴,𝑆+ 𝐵− 𝐴+ 10-50

1 𝑔𝐴,𝑆− 𝐵+ 𝐴+ 10-50
𝐻1− (𝐴) =
𝐴 𝑛𝐴,𝐴
1+( ) 𝑔𝐴,𝑆+ 𝐵+ 𝐴+ 10-50
𝐴𝐴,0
𝑔𝐵,0 1-10
𝐻1+ (𝐴) = 1 − 𝐻1− (𝐴)
𝑔𝐵,𝐴+ 10-50

1 𝑘𝐴 , 𝑘𝐵 0.01-0.1
𝐻2− (𝐴) =
𝐴 𝑛𝐴,𝐵 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1+( ) 1-6
𝐴𝐵,0 𝑛𝐴,𝐴
From
𝐻2+ (𝐴) = 1 − 𝐻2− (𝐴) 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐴𝐴,0 functional
rule

22
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝐴, 𝐵) − 𝑘𝐵 . 𝐵
𝑑𝑡

𝐺𝐴 (𝑆, 𝐵) 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵−

= 𝑔𝐴,𝑆− 𝐵− . 𝐻 − (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻 + (𝑆). 𝐻1− (𝐵) 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆− 𝐵+
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻 − (𝑆). 𝐻1+ (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻 + (𝑆). 𝐻1+ (𝐵) 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵+

𝐺𝐵 (𝐴, 𝐵) 𝑔𝐵,𝐴− 𝐵− < 𝑔𝐵,𝐴+ 𝐵−

= 𝑔𝐵,𝐴− 𝐵− . 𝐻 − (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝐴+ 𝐵− . 𝐻 + (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝐴− 𝐵− < 𝑔𝐵,𝐴− 𝐵+
+ 𝑔𝐵,𝐴− 𝐵+ . 𝐻 − (𝐴). 𝐻2+ (𝐵)
+ 𝑔𝐵,𝐴+ 𝐵+ . 𝐻 + (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝐴− 𝐵− < 𝑔𝐵,𝐴+ 𝐵+

1 𝑔𝐴,𝑆− 𝐵− 1-10
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( ) 𝑔𝐴,𝑆+ 𝐵− 10-50
𝑆𝐴,0
𝑔𝐴,𝑆− 𝐵+ 10-50
𝐻 + (𝑆) = 1 − 𝐻 − (𝑆)
𝑔𝐴,𝑆+ 𝐵+ 10-50
1 𝑔𝐵,𝐴− 𝐵− 1-10
𝐻1− (𝐵) =
𝐵 𝑛𝐵,𝐴
1+( ) 𝑔𝐵,𝐴+ 𝐵− 10-50
𝐵𝐴,0
𝑔𝐵,𝐴− 𝐵+ 10-50
𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵)
𝑔𝐵,𝐴+ 𝐵+ 10-50
− (𝐴)
1
𝐻 =
𝐴 𝑛𝐴,𝐵 𝑘𝐴 , 𝑘𝐵 0.01-0.1
1+( )
𝐴𝐵,0 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1-6
+ (𝐴) − (𝐴)
𝑛𝐵,𝐵
𝐻 =1−𝐻
From
𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐵𝐵,0 functional
1
𝐻2− (𝐵) = rule
𝐵 𝑛𝐵,𝐵
1+( )
𝐵𝐵,0

𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵)

23
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵, 𝐶) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝑔𝐵,0 + 𝑔𝐵,𝐴− . 𝐻1− (𝐴) − 𝑘𝐵 . 𝐵 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆+ 𝐵− 𝐶−
𝑑𝑡

𝑑𝐶 𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵+ 𝐶−

= 𝑔𝐶,0 + 𝑔𝐶,𝐴+ . 𝐻2+ (𝐴) − 𝑘𝐶 . 𝐶
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆− 𝐵− 𝐶+
𝐺𝐴 (𝑆, 𝐵, 𝐶)
= 𝑔𝐴,𝑆− 𝐵− 𝐶− . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻 − (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶− . 𝐻 + (𝑆). 𝐻− (𝐵). 𝐻− (𝐶)
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶− . 𝐻 − (𝑆). 𝐻+ (𝐵). 𝐻− (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆+ 𝐵− 𝐶+
+ 𝑔𝐴,𝑆− 𝐵− 𝐶+ . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶− . 𝐻 + (𝑆). 𝐻+ (𝐵). 𝐻− (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆− 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶+ . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶+ . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻 + (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻 + (𝐶)
𝑔𝐵,0 < 𝑔𝐵,𝐴−
1
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴 𝑔𝐶,0 < 𝑔𝐶,𝐴+
1+( )
𝑆𝐴,0
𝑔𝐴,𝑆− 𝐵− 𝐶− 1-10
𝐻 + (𝑆) = 1 − 𝐻 − (𝑆)
𝑔𝐴,𝑆+ 𝐵− 𝐶− 10-50
1
𝐻 − (𝐵) = 𝑔𝐴,𝑆− 𝐵+ 𝐶− 0.1-1
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0
𝑔𝐴,𝑆− 𝐵− 𝐶+ 10-50
𝐻 + (𝐵) = 1 − 𝐻− (𝐵) 𝑔𝐴,𝑆+ 𝐵− 𝐶+ 10-50
1 𝑔𝐵,0 1-10
𝐻 − (𝐶) =
𝐶 𝑛𝐶,𝐴
1+( ) 𝑔𝐵,𝐴− 10-50
𝐶𝐴,0
𝑔𝐶,0 1-10
𝐻 + (𝐶) = 1 − 𝐻 − (𝐶)
𝑔𝐶,𝐴+ 10-50
1
𝐻1− (𝐴) =
𝐴 𝑛𝐴,𝐵 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
1+( )
𝐴𝐵,0 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1-6
𝑛𝐶,𝐴 , 𝑛𝐴,𝐶
𝐻1+ (𝐴) =1− 𝐻1− (𝐴)
From
𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
1
𝐻2− (𝐴) = 𝐶𝐴,0 , 𝐴𝐶,0 functional
𝐴 𝑛𝐴,𝐶
1+( ) rule
𝐴𝐶,0

𝐻2+ (𝐴) = 1 − 𝐻2− (𝐴)

24
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵, 𝐶) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝑔𝐵,0 + 𝑔𝐵,𝐴− . 𝐻1− (𝐴) − 𝑘𝐵 . 𝐵
𝑑𝑡 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆+ 𝐵− 𝐶−

𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐴− . 𝐻2− (𝐴) − 𝑘𝐶 . 𝐶 𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵+ 𝐶−
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵− 𝐶+
𝐺𝐴 (𝑆, 𝐵, 𝐶)
= 𝑔𝐴,𝑆− 𝐵− 𝐶− . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻 − (𝐶)
𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶− . 𝐻 + (𝑆). 𝐻− (𝐵). 𝐻− (𝐶)
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶− . 𝐻 − (𝑆). 𝐻+ (𝐵). 𝐻− (𝐶)
𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵− 𝐶+
+ 𝑔𝐴,𝑆− 𝐵− 𝐶+ . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶− . 𝐻 + (𝑆). 𝐻+ (𝐵). 𝐻− (𝐶)
𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶+ . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶+ . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻 + (𝐶)
𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻 + (𝐶)
𝑔𝐵,0 < 𝑔𝐵,𝐴−
− (𝑆)
1
𝐻 =
𝑆 𝑛𝑆,𝐴 𝑔𝐶,0 < 𝑔𝐶,𝐴−
1+( )
𝑆𝐴,0

𝐻 + (𝑆) = 1 − 𝐻 − (𝑆)
𝑔𝐴,𝑆− 𝐵− 𝐶− 1-10
1
𝐻 − (𝐵) = 𝑔𝐴,𝑆+ 𝐵− 𝐶− 10-50
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐴,𝑆− 𝐵+ 𝐶− 0.1-1

𝐻 + (𝐵) = 1 − 𝐻− (𝐵) 𝑔𝐴,𝑆− 𝐵− 𝐶+ 0.1-1

1 𝑔𝐴,𝑆− 𝐵+ 𝐶+ 0.1-1
𝐻 − (𝐶) =
𝐶 𝑛𝐶,𝐴
1+( ) 𝑔𝐵,0 1-10
𝐶𝐴,0
𝑔𝐵,𝐴− 10-50
𝐻 + (𝐶) = 1 − 𝐻 − (𝐶)
𝑔𝐶,0 1-10
1
𝐻1− (𝐴) = 𝑔𝐶,𝐴− 10-50
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0
𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
𝐻1+ (𝐴) = 1 − 𝐻1− (𝐴) 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1-6
𝑛𝐶,𝐴 , 𝑛𝐴,𝐶
1 From
𝐻2− (𝐴) =
𝐴 𝑛𝐴,𝐶 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
1+( )
𝐴𝐶,0 𝐶𝐴,0 , 𝐴𝐶,0 functional
rule
𝐻2+ (𝐴) = 1 − 𝐻2− (𝐴)

25
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝐴, 𝐶) − 𝑘𝐵 . 𝐵
𝑑𝑡

𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐵+ . 𝐻2+ (𝐵) − 𝑘𝐶 . 𝐶
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵−
𝐺𝐴 (𝑆, 𝐵)
= 𝑔𝐴,𝑆− 𝐵− . 𝐻 − (𝑆). 𝐻1− (𝐵) 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆− 𝐵+
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻 + (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻 − (𝑆). 𝐻1+ (𝐵) 𝑔𝐴,𝑆− 𝐵− = 𝑔𝐴,𝑆+ 𝐵+
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻 + (𝑆). 𝐻1+ (𝐵)
𝑔𝐵,𝐴− 𝐶− > 𝑔𝐵,𝐴+ 𝐶−
𝐺𝐵 (𝐴, 𝐶)
= 𝑔𝐵,𝐴− 𝐶− . 𝐻 − (𝐴). 𝐻 − (𝐶) 𝑔𝐵,𝐴− 𝐶− < 𝑔𝐵,𝐴− 𝐶+
+ 𝑔𝐵,𝐴+ 𝐶− . 𝐻 + (𝐴). 𝐻− (𝐶)
+ 𝑔𝐵,𝐴− 𝐶+ . 𝐻 − (𝐴). 𝐻+ (𝐶) 𝑔𝐵,𝐴− 𝐶− = 𝑔𝐵,𝐴+ 𝐶+
+ 𝑔𝐵,𝐴+ 𝐶+ . 𝐻 + (𝐴). 𝐻+ (𝐶)
𝑔𝐶,0 < 𝑔𝐶,𝐵+
1
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴 𝑔𝐴,𝑆− 𝐵− 1-10
1+( )
𝑆𝐴,0
𝑔𝐴,𝑆+ 𝐵− 10-50
+ (𝑆) − (𝑆)
𝐻 =1−𝐻
𝑔𝐴,𝑆− 𝐵+ 0.1-1
1
𝐻1− (𝐵) = 𝑔𝐵,𝐴− 𝐶− 1-10
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐵,𝐴+ 𝐶− 0.1-1

𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵) 𝑔𝐵,𝐴− 𝐶+ 10-50

1 𝑔𝐶,0 1-10
𝐻 − (𝐴) =
𝐴 𝑛𝐴,𝐵 𝑔𝐶,𝐵+ 10-50
1+( )
𝐴𝐵,0
𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
+ (𝐴) − (𝐴)
𝐻 =1−𝐻
𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1-6
1 𝑛𝐶,𝐵 , 𝑛𝐵,𝐶 ,
𝐻 − (𝐶) = From
𝐶 𝑛𝐶,𝐵
1+( ) 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐶𝐵,0
𝐶𝐵,0 , 𝐵𝐶,0 functional
rule
𝐻 + (𝐶) = 1 − 𝐻 − (𝐶)

1
𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐶
1+( )
𝐵𝐶,0

𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵)

26
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝐴, 𝐶) − 𝑘𝐵 . 𝐵
𝑑𝑡

𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐵− . 𝐻2− (𝐵) − 𝑘𝐶 . 𝐶 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵−
𝑑𝑡

𝐺𝐴 (𝑆, 𝐵) 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆− 𝐵+

= 𝑔𝐴,𝑆− 𝐵− . 𝐻 − (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻 + (𝑆). 𝐻1− (𝐵) 𝑔𝐴,𝑆− 𝐵− = 𝑔𝐴,𝑆+ 𝐵+
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻 − (𝑆). 𝐻1+ (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻 + (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝐴− 𝐶− > 𝑔𝐵,𝐴+ 𝐶−

𝐺𝐵 (𝐴, 𝐶) 𝑔𝐵,𝐴− 𝐶− > 𝑔𝐵,𝐴− 𝐶+

= 𝑔𝐵,𝐴− 𝐶− . 𝐻 − (𝐴). 𝐻 − (𝐶)
+ 𝑔𝐵,𝐴+ 𝐶− . 𝐻 + (𝐴). 𝐻− (𝐶) 𝑔𝐵,𝐴− 𝐶− > 𝑔𝐵,𝐴+ 𝐶+
+ 𝑔𝐵,𝐴− 𝐶+ . 𝐻 − (𝐴). 𝐻+ (𝐶)
+ 𝑔𝐵,𝐴+ 𝐶+ . 𝐻 + (𝐴). 𝐻+ (𝐶) 𝑔𝐶,0 < 𝑔𝐶,𝐵−

1 𝑔𝐴,𝑆− 𝐵− 1-10
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0 𝑔𝐴,𝑆+ 𝐵− 10-50

𝐻 + (𝑆) = 1 − 𝐻 − (𝑆) 𝑔𝐴,𝑆− 𝐵+ 0.1-1

𝑔𝐵,𝐴− 𝐶− 1-10
1
𝐻1− (𝐵) =
𝐵 𝑛𝐵,𝐴 𝑔𝐵,𝐴+ 𝐶− 0.1-1
1+( )
𝐵𝐴,0
𝑔𝐵,𝐴− 𝐶+ 0.1-1
𝐻1+ (𝐵) =1− 𝐻1− (𝐵)
𝑔𝐵,𝐴+ 𝐶+ 0.1-1
1
𝐻 − (𝐴) = 𝑔𝐶,0 1-10
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0 𝑔𝐶,𝐵− 10-50

𝐻 + (𝐴) = 1 − 𝐻 − (𝐴) 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1

𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1 1-6
𝐻 − (𝐶)
= 𝑛𝐶,𝐵 , 𝑛𝐵,𝐶
𝐶 𝑛𝐶,𝐵 From
1+( )
𝐶𝐵,0 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐶𝐵,0 , 𝐵𝐶,0 functional
𝐻 + (𝐶) = 1 − 𝐻 − (𝐶) rule
1
𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐶
1+( )
𝐵𝐶,0

𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵)

27
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵, 𝐶) − 𝑘𝐴 . 𝐴 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆
𝑑𝑡

𝑑𝐵 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝐵

= 𝑔𝐵,0 + 𝑔𝐵,𝐴+ . 𝐻1+ (𝐴) − 𝑘𝐵 . 𝐵
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝐶
𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐴+ . 𝐻2+ (𝐴) − 𝑘𝐶 . 𝐶 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆𝐵
𝑑𝑡

𝐺𝐴 (𝑆, 𝐵, 𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆𝐶

= 𝑔𝐴,𝑆− 𝐵− 𝐶− . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻 − (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶− . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻 − (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝐵𝐶
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶− . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻 − (𝐶)
+ 𝑔𝐴,𝑆− 𝐵− 𝐶+ . 𝐻 − (𝑆). 𝐻− (𝐵). 𝐻+ (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆𝐵𝐶
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶− . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻 − (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶+ . 𝐻 + (𝑆). 𝐻− (𝐵). 𝐻+ (𝐶) 𝑔𝐵,0 < 𝑔𝐵,𝐴+
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶+ . 𝐻 − (𝑆). 𝐻+ (𝐵). 𝐻+ (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ . 𝐻 + (𝑆). 𝐻+ (𝐵). 𝐻+ (𝐶) 𝑔𝐶,0 < 𝑔𝐶,𝐴+

1 𝑔𝐴,𝑆− 𝐵− 𝐶− 1-10
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( ) 𝑔𝐴,𝑆+ 𝐵− 𝐶−
𝑆𝐴,0 10-50
𝐻 + (𝑆) = 1 − 𝐻 − (𝑆)
𝑔𝐴,𝑆− 𝐵+ 𝐶− 10-50
1
𝐻 − (𝐵) = 𝑔𝐴,𝑆− 𝐵− 𝐶+ 10-50
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐴,𝑆+ 𝐵+ 𝐶− 10-50

𝐻 + (𝐵) = 1 − 𝐻− (𝐵) 𝑔𝐴,𝑆+ 𝐵− 𝐶+ 10-50

1 𝑔𝐴,𝑆− 𝐵+ 𝐶+ 10-50
𝐻 − (𝐶) =
𝐶 𝑛𝐶,𝐴 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ 10-50
1+( )
𝐶𝐴,0
𝑔𝐵,0 1-10
𝐻 + (𝐶) = 1 − 𝐻 − (𝐶)
𝑔𝐵,𝐴+ 10-50
1
𝐻1− (𝐴) = 𝑔𝐶,0 1-10
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0 𝑔𝐶,𝐴+ 10-50

𝐻1+ (𝐴) = 1 − 𝐻1− (𝐴) 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1

𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1 1-6
𝐻2− (𝐴) = 𝑛𝐶,𝐴 , 𝑛𝐴,𝐶
𝐴 𝑛𝐴,𝐶
1+( ) From
𝐴𝐶,0
𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐶𝐴,0 , 𝐴𝐶,0 functional
𝐻2+ (𝐴) = 1 − 𝐻2− (𝐴)
rule

28
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵, 𝐶) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆+ 𝐵− 𝐶−

= 𝑔𝐵,0 + 𝑔𝐵,𝐴+ . 𝐻1+ (𝐴) − 𝑘𝐵 . 𝐵
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵− 𝐶+
𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐴− . 𝐻2− (𝐴) − 𝑘𝐶 . 𝐶 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆− 𝐵+ 𝐶−
𝑑𝑡

𝐺𝐴 (𝑆, 𝐵, 𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵− 𝐶+

= 𝑔𝐴,𝑆− 𝐵− 𝐶− . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻 − (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶− . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻 − (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆+ 𝐵+ 𝐶−
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶− . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻 − (𝐶)
+ 𝑔𝐴,𝑆− 𝐵− 𝐶+ . 𝐻 − (𝑆). 𝐻− (𝐵). 𝐻+ (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆− 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶− . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻 − (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶+ . 𝐻 + (𝑆). 𝐻− (𝐵). 𝐻+ (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶+ . 𝐻 − (𝑆). 𝐻+ (𝐵). 𝐻+ (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ . 𝐻 + (𝑆). 𝐻+ (𝐵). 𝐻+ (𝐶) 𝑔𝐵,0 < 𝑔𝐵,𝐴+

1 𝑔𝐶,0 < 𝑔𝐶,𝐴−

𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0
𝐻 + (𝑆) = 1 − 𝐻 − (𝑆) 𝑔𝐴,𝑆− 𝐵− 𝐶− 1-10
1 𝑔𝐴,𝑆+ 𝐵− 𝐶− 10-50
𝐻 − (𝐵) =
𝐵 𝑛𝐵,𝐴
1+( ) 𝑔𝐴,𝑆− 𝐵− 𝐶+ 0.1-1
𝐵𝐴,0
𝑔𝐴,𝑆− 𝐵+ 𝐶− 10-50
𝐻 + (𝐵) = 1 − 𝐻− (𝐵)
𝑔𝐴,𝑆+ 𝐵+ 𝐶− 10-50
− (𝐶)
1
𝐻 =
𝐶 𝑛𝐶,𝐴 𝑔𝐵,0 1-10
1+( )
𝐶𝐴,0
𝑔𝐵,𝐴+ 10-50
+ (𝐶) − (𝐶)
𝐻 =1−𝐻
𝑔𝐶,0 1-10
1 𝑔𝐶,𝐴− 10-50
𝐻1− (𝐴) =
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
𝐻1+ (𝐴) = 1 − 𝐻1− (𝐴) 𝑛𝐶,𝐴 , 𝑛𝐴,𝐶
1-6

1 From
𝐻2− (𝐴) = 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐴 𝑛𝐴,𝐶
1+( ) 𝐶𝐴,0 , 𝐴𝐶,0 functional
𝐴𝐶,0
rule
𝐻2+ (𝐴) = 1 − 𝐻2− (𝐴)

29
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝐴, 𝐶) − 𝑘𝐵 . 𝐵
𝑑𝑡

𝑑𝐶 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵−

= 𝑔𝐶,0 + 𝑔𝐶,𝐵+ . 𝐻2+ (𝐵) − 𝑘𝐶 . 𝐶
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆− 𝐵+
𝐺𝐴 (𝑆, 𝐵)
= 𝑔𝐴,𝑆− 𝐵− . 𝐻 − (𝑆). 𝐻1− (𝐵) 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵+
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻 + (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻 − (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝐴− 𝐶− < 𝑔𝐵,𝐴+ 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻 + (𝑆). 𝐻1+ (𝐵)
𝑔𝐵,𝐴− 𝐶− < 𝑔𝐵,𝐴− 𝐶+
𝐺𝐵 (𝐴, 𝐶)
= 𝑔𝐵,𝐴− 𝐶− . 𝐻 − (𝐴). 𝐻 − (𝐶) 𝑔𝐵,𝐴− 𝐶− < 𝑔𝐵,𝐴+ 𝐶+
+ 𝑔𝐵,𝐴+ 𝐶− . 𝐻 + (𝐴). 𝐻− (𝐶)
+ 𝑔𝐵,𝐴− 𝐶+ . 𝐻 − (𝐴). 𝐻+ (𝐶) 𝑔𝐶,0 < 𝑔𝐶,𝐵+
+ 𝑔𝐵,𝐴+ 𝐶+ . 𝐻 + (𝐴). 𝐻+ (𝐶)
𝑔𝐴,𝑆− 𝐵− 1-10
− (𝑆)
1
𝐻 =
𝑆 𝑛𝑆,𝐴 𝑔𝐴,𝑆+ 𝐵− 10-50
1+( )
𝑆𝐴,0
𝑔𝐴,𝑆− 𝐵+ 10-50
+ (𝑆) − (𝑆)
𝐻 =1−𝐻
𝑔𝐴,𝑆+ 𝐵+ 10-50
1
𝐻1− (𝐵) = 𝑔𝐵,𝐴− 𝐶− 1-10
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐵,𝐴+ 𝐶− 10-50

𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵) 𝑔𝐵,𝐴− 𝐶+ 10-50

1 𝑔𝐵,𝐴+ 𝐶+ 10-50
𝐻 − (𝐴) =
𝐴 𝑛𝐴,𝐵 𝑔𝐶,0 1-10
1+( )
𝐴𝐵,0
𝑔𝐶,𝐵+ 10-50
+ (𝐴) − (𝐴)
𝐻 =1−𝐻
𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
1 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
𝐻 − (𝐶) = 1-6
𝐶 𝑛𝐶,𝐵 𝑛𝐶,𝐵 , 𝑛𝐵,𝐶
1+( )
𝐶𝐵,0 From
𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐻 + (𝐶) = 1 − 𝐻 − (𝐶) 𝐶𝐵,0 , 𝐵𝐶,0 functional
rule
1
𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐶
1+( )
𝐵𝐶,0

𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵)

30
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝐴, 𝐶) − 𝑘𝐵 . 𝐵
𝑑𝑡

𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐵− . 𝐻2− (𝐵) − 𝑘𝐶 . 𝐶 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵−
𝑑𝑡

𝐺𝐴 (𝑆, 𝐵) 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆− 𝐵+

= 𝑔𝐴,𝑆− 𝐵− . 𝐻 − (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻 + (𝑆). 𝐻1− (𝐵) 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+ 𝐵+
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻 − (𝑆). 𝐻1+ (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻 + (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝐴− 𝐶− < 𝑔𝐵,𝐴+ 𝐶−

𝐺𝐵 (𝐴, 𝐶) 𝑔𝐵,𝐴− 𝐶− > 𝑔𝐵,𝐴− 𝐶+

= 𝑔𝐵,𝐴− 𝐶− . 𝐻 − (𝐴). 𝐻 − (𝐶)
+ 𝑔𝐵,𝐴+ 𝐶− . 𝐻 + (𝐴). 𝐻− (𝐶) 𝑔𝐵,𝐴− 𝐶− = 𝑔𝐵,𝐴𝐶
+ 𝑔𝐵,𝐴− 𝐶+ . 𝐻 − (𝐴). 𝐻+ (𝐶)
+ 𝑔𝐵,𝐴+ 𝐶+ . 𝐻 + (𝐴). 𝐻+ (𝐶) 𝑔𝐶,0 < 𝑔𝐶,𝐵−

1 𝑔𝐴,𝑆− 𝐵− 1-10
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0 𝑔𝐴,𝑆+ 𝐵− 10-50

𝐻 + (𝑆) = 1 − 𝐻 − (𝑆) 𝑔𝐴,𝑆− 𝐵+ 10-50

𝑔𝐴,𝑆+ 𝐵+ 10-50
1
𝐻1− (𝐵) =
𝐵 𝑛𝐵,𝐴 𝑔𝐵,𝐴− 𝐶− 1-10
1+( )
𝐵𝐴,0
𝑔𝐵,𝐴+ 𝐶− 10-50
𝐻1+ (𝐵) =1− 𝐻1− (𝐵)
𝑔𝐵,𝐴− 𝐶+ 0.1-1
1
𝐻 − (𝐴) = 𝑔𝐶,0 1-10
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0 𝑔𝐶,𝐵− 10-50

𝐻 + (𝐴) = 1 − 𝐻 − (𝐴) 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1

𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1 1-6
𝐻 − (𝐶)
= 𝑛𝐶,𝐵 , 𝑛𝐵,𝐶
𝐶 𝑛𝐶,𝐵 From
1+( )
𝐶𝐵,0 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐶𝐵,0 , 𝐵𝐶,0 functional
𝐻 + (𝐶) = 1 − 𝐻 − (𝐶) rule
1
𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐶
1+( )
𝐵𝐶,0

𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵)

31
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝑆, 𝐴, 𝐵) − 𝑘𝐵 . 𝐵 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+𝐵−
𝑑𝑡

𝐺𝐴 (𝑆, 𝐵) 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆−𝐵+

= 𝑔𝐴,𝑆− 𝐵− . 𝐻1− (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻1+ (𝑆). 𝐻1− (𝐵) 𝑔𝐴,𝑆−𝐵− = 𝑔𝐴,𝑆+ 𝐵+
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻1− (𝑆). 𝐻1+ (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻1+ (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− > 𝑔𝐵,𝑆+ 𝐴− 𝐵−

𝐺𝐵 (𝑆, 𝐴, 𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− > 𝑔𝐵,𝑆− 𝐴+ 𝐵−

= 𝑔𝐵,𝑆− 𝐴− 𝐵− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆− 𝐴+𝐵− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵)
𝑔𝐵,𝑆− 𝐴− 𝐵− < 𝑔𝐵,𝑆− 𝐴− 𝐵+
+ 𝑔𝐵,𝑆− 𝐴−𝐵+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− > 𝑔𝐵,𝑆+ 𝐴+ 𝐵−
+ 𝑔𝐵,𝑆− 𝐴+𝐵+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− = 𝑔𝐵,𝑆− 𝐴+ 𝐵+
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵)
𝑔𝐵,𝑆− 𝐴− 𝐵− = 𝑔𝐵,𝑆+ 𝐴− 𝐵+
1
𝐻1− (𝑆) =
𝑆 𝑛𝑆,𝐴 𝑔𝐵,𝑆− 𝐴− 𝐵− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+
1+( )
𝑆𝐴,0

𝐻1+ (𝑆) = 1 − 𝐻1− (𝑆) 𝑔𝐴,𝑆− 𝐵− 1-10

1 𝑔𝐴,𝑆+ 𝐵− 10-50
𝐻1− (𝐵) =
𝐵 𝑛𝐵,𝐴
1+( ) 𝑔𝐴,𝑆− 𝐵+ 0.1-1
𝐵𝐴,0

𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 1-10

1 𝑔𝐵,𝑆+ 𝐴− 𝐵− 0.1-1
𝐻 − (𝐴) =
𝐴 𝑛𝐴,𝐵
1+( ) 𝑔𝐵,𝑆− 𝐴+ 𝐵− 0.1-1
𝐴𝐵,0
𝑔𝐵,𝑆− 𝐴− 𝐵+ 10-50
𝐻 + (𝐴) = 1 − 𝐻 − (𝐴)
𝑔𝐵,𝑆+ 𝐴+ 𝐵− 0.1-1
1
𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐵 𝑘𝐴 , 𝑘𝐵 0.01-0.1
1+( )
𝐵𝐵,0
𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1-6
𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵) 𝑛𝐵,𝐵 , 𝑛𝑆,𝐵
From
1 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐻2− (𝑆) =
𝑆 𝑛𝑆,𝐵 𝐵𝐵,0 , 𝑆𝐵,0 functional
1+( )
𝑆𝐵,0
rule
𝐻2+ (𝑆) = 1 − 𝐻2− (𝑆)

32
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+𝐵−

= 𝐺𝐵 (𝑆, 𝐴, 𝐵) − 𝑘𝐵 . 𝐵
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆−𝐵+
𝐺𝐴 (𝑆, 𝐵)
= 𝑔𝐴,𝑆− 𝐵− . 𝐻1− (𝑆). 𝐻1− (𝐵)
𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+𝐵+
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻1+ (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻1− (𝑆). 𝐻1+ (𝐵)
𝑔𝐵,𝑆−𝐴− 𝐵− < 𝑔𝐵,𝑆+ 𝐴− 𝐵−
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻1+ (𝑆). 𝐻1+ (𝐵)

𝐺𝐵 (𝑆, 𝐴, 𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− > 𝑔𝐵,𝑆− 𝐴+ 𝐵−

= 𝑔𝐵,𝑆− 𝐴− 𝐵− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− < 𝑔𝐵,𝑆− 𝐴− 𝐵+
+ 𝑔𝐵,𝑆− 𝐴+𝐵− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆− 𝐴−𝐵+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵−
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆− 𝐴+𝐵+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆− 𝐴+ 𝐵+
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− < 𝑔𝐵,𝑆+ 𝐴− 𝐵+

1 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+

𝐻1− (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0
𝑔𝐴,𝑆− 𝐵− 1-10
𝐻1+ (𝑆) =1− 𝐻1− (𝑆)
𝑔𝐴,𝑆+ 𝐵− 0.1-1
1
𝐻1− (𝐵) = 𝑔𝐴,𝑆− 𝐵+ 0.1-1
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐴,𝑆+ 𝐵+ 0.1-1
𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− 1-10
1 𝑔𝐵,𝑆+ 𝐴−𝐵− 10-50
𝐻 − (𝐴) =
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0 𝑔𝐵,𝑆− 𝐴+𝐵− 0.1-1

𝐻 + (𝐴) = 1 − 𝐻 − (𝐴) 𝑔𝐵,𝑆− 𝐴−𝐵+ 10-50

1 𝑔𝐵,𝑆+ 𝐴−𝐵+ 10-50

𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐵
1+( ) 𝑘𝐴 , 𝑘𝐵 0.01-0.1
𝐵𝐵,0
𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵) 1-6
𝑛𝐵,𝐵 , 𝑛𝑆,𝐵
1 From
𝐻2− (𝑆) = 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝑆 𝑛𝑆,𝐵
1+( ) 𝐵𝐵,0 , 𝑆𝐵,0 functional
𝑆𝐵,0
rule
𝐻2+ (𝑆) = 1 − 𝐻2− (𝑆)

33
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵
= 𝐺𝐵 (𝑆, 𝐴, 𝐵) − 𝑘𝐵 . 𝐵
𝑑𝑡 𝑔𝐴,𝑆− 𝐵− < 𝑔𝐴,𝑆+𝐵−

𝐺𝐴 (𝑆, 𝐵) 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆−𝐵+

= 𝑔𝐴,𝑆− 𝐵− . 𝐻1− (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻1+ (𝑆). 𝐻1− (𝐵)
𝑔𝐴,𝑆−𝐵− = 𝑔𝐴,𝑆+ 𝐵+
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻1− (𝑆). 𝐻1+ (𝐵)
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻1+ (𝑆). 𝐻1+ (𝐵)
𝑔𝐵,𝑆−𝐴− 𝐵− < 𝑔𝐵,𝑆+ 𝐴− 𝐵−
𝐺𝐵 (𝑆, 𝐴, 𝐵)
= 𝑔𝐵,𝑆− 𝐴− 𝐵− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− > 𝑔𝐵,𝑆− 𝐴+ 𝐵−
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆− 𝐴+𝐵− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− < 𝑔𝐵,𝑆− 𝐴− 𝐵+
+ 𝑔𝐵,𝑆− 𝐴−𝐵+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵−
+ 𝑔𝐵,𝑆− 𝐴+𝐵+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆− 𝐴+ 𝐵+
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵)
𝑔𝐵,𝑆−𝐴− 𝐵− < 𝑔𝐵,𝑆+ 𝐴− 𝐵+
1
𝐻1− (𝑆) = 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0
𝑔𝐴,𝑆− 𝐵− 1-10
𝐻1+ (𝑆) = 1 − 𝐻1− (𝑆)
𝑔𝐴,𝑆+ 𝐵− 10-50
1
𝐻1− (𝐵) =
𝐵 𝑛𝐵,𝐴 𝑔𝐴,𝑆− 𝐵+ 0.1-1
1+( )
𝐵𝐴,0
𝑔𝐵,𝑆− 𝐴−𝐵− 1-10
𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵)
𝑔𝐵,𝑆+ 𝐴−𝐵− 10-50
1
𝐻 − (𝐴) =
𝐴 𝑛𝐴,𝐵 𝑔𝐵,𝑆− 𝐴+𝐵− 0.1-1
1+( )
𝐴𝐵,0
𝑔𝐵,𝑆− 𝐴−𝐵+ 10-50
𝐻 + (𝐴) = 1 − 𝐻 − (𝐴)
𝑔𝐵,𝑆+ 𝐴−𝐵+ 10-50
1
𝐻2− (𝐵) = 𝑘𝐴 , 𝑘𝐵 0.01-0.1
𝐵 𝑛𝐵,𝐵
1+( )
𝐵𝐵,0
𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1-6
𝐻2+ (𝐵) =1− 𝐻2− (𝐵)
𝑛𝐵,𝐵 , 𝑛𝑆,𝐵
From
1 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝐻2− (𝑆) =
𝑆 𝑛𝑆,𝐵 𝐵𝐵,0 , 𝑆𝐵,0 functional
1+( )
𝑆𝐵,0 rule

𝐻2+ (𝑆) = 1 − 𝐻2− (𝑆)

34
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡

𝑑𝐵 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+𝐵−

= 𝐺𝐵 (𝑆, 𝐴, 𝐵) − 𝑘𝐵 . 𝐵
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆−𝐵+
𝐺𝐴 (𝑆, 𝐵)
= 𝑔𝐴,𝑆− 𝐵− . 𝐻1− (𝑆). 𝐻1− (𝐵)
𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+𝐵+
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻1+ (𝑆). 𝐻1− (𝐵)
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻1− (𝑆). 𝐻1+ (𝐵)
𝑔𝐵,𝑆−𝐴− 𝐵− > 𝑔𝐵,𝑆+ 𝐴− 𝐵−
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻1+ (𝑆). 𝐻1+ (𝐵)

𝐺𝐵 (𝑆, 𝐴, 𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− > 𝑔𝐵,𝑆− 𝐴+ 𝐵−

= 𝑔𝐵,𝑆− 𝐴−𝐵− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− < 𝑔𝐵,𝑆− 𝐴− 𝐵+
+ 𝑔𝐵,𝑆− 𝐴+ 𝐵− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆− 𝐴− 𝐵+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆−𝐴− 𝐵− > 𝑔𝐵,𝑆+ 𝐴+ 𝐵−
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵)
+ 𝑔𝐵,𝑆− 𝐴+ 𝐵+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆− 𝐴+ 𝐵+
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵)
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆+ 𝐴− 𝐵+

1 𝑔𝐵,𝑆− 𝐴−𝐵− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+

𝐻1− (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0
𝑔𝐴,𝑆− 𝐵− 1-10
𝐻1+ (𝑆) =1− 𝐻1− (𝑆)
𝑔𝐴,𝑆+ 𝐵− 0.1-1
1
𝐻1− (𝐵) = 𝑔𝐴,𝑆− 𝐵+ 0.1-1
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐴,𝑆+ 𝐵+ 0.1-1
𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴−𝐵− 1-10
1 𝑔𝐵,𝑆+ 𝐴−𝐵− 0.1-1
𝐻 − (𝐴) =
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0 𝑔𝐵,𝑆− 𝐴+𝐵− 0.1-1

𝐻 + (𝐴) = 1 − 𝐻 − (𝐴) 𝑔𝐵,𝑆− 𝐴−𝐵+ 10-50

1 𝑔𝐵,𝑆+ 𝐴+𝐵− 0.1-1

𝐻2− (𝐵) =
𝐵 𝑛𝐵,𝐵
1+( ) 𝑘𝐴 , 𝑘𝐵 0.01-0.1
𝐵𝐵,0
𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵) 1-6
𝑛𝐵,𝐵 , 𝑛𝑆,𝐵
1 From
𝐻2− (𝑆) = 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , half-
𝑆 𝑛𝑆,𝐵
1+( ) 𝐵𝐵,0 , 𝑆𝐵,0 functional
𝑆𝐵,0
rule
𝐻2+ (𝑆) = 1 − 𝐻2− (𝑆)

35
Network
Dynamical Equations Parameter Ranges
Topology
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡
𝑑𝐵
= 𝐺𝐵 (𝑆, 𝐴, 𝐵, 𝐶) − 𝑘𝐵 . 𝐵 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+ 𝐵−
𝑑𝑡
𝑑𝐶 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆− 𝐵+
= 𝑔𝐶,0 + 𝑔𝐶,𝐵− . 𝐻3− (𝐵) − 𝑘𝐶 . 𝐶 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+ 𝐵+
𝑑𝑡
𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶−
𝐺𝐴 (𝑆, 𝐵) = 𝑔𝐴,𝑆− 𝐵− . 𝐻1− (𝑆). 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− > 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻1+ (𝑆). 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶−
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻1− (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− > 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻1+ (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶−
𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆− 𝐴+ 𝐵+ 𝐶−
𝐺𝐵 (𝑆, 𝐴, 𝐵, 𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶−
= 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− > 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶+
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶+
+ 𝑔𝐵,𝑆− 𝐴+𝐵− 𝐶− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆− 𝐴−𝐵+ 𝐶− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶−
+ 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶+
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆− 𝐴+𝐵+ 𝐶− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆− 𝐴+ 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶) 𝑔𝐶,0 < 𝑔𝐶,𝐵−
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶)
𝑔𝐴,𝑆− 𝐵− 1-10
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶)
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶) 𝑔𝐴,𝑆+ 𝐵− 0.1-1
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶) 𝑔𝐴,𝑆− 𝐵+ 0.1-1
+ 𝑔𝐵,𝑆− 𝐴+ 𝐵+ 𝐶+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶)
𝑔𝐴,𝑆+ 𝐵+ 0.1-1
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶)
𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− 1-10
1
𝐻1− (𝑆) = ; 𝐻1+ (𝑆) = 1 − 𝐻1− (𝑆) 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶− 10-50
𝑆 𝑛𝑆,𝐴
1+( ) 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶− 0.1-1
𝑆𝐴,0
1 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶− 10-50
𝐻1− (𝐵) = ; 𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵)
𝐵 𝑛𝐵,𝐴
1+( ) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶+ 0.1-1
𝐵𝐴,0
1 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶− 10-50
𝐻 − (𝐴) = ; 𝐻 + (𝐴) = 1 − 𝐻 − (𝐴)
𝐴 𝑛𝐴,𝐵
1+( ) 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶+ 0.1-1
𝐴𝐵,0
1 𝑔𝐶,0 1-10
𝐻2− (𝐵) = ; 𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵)
𝐵 𝑛𝐵,𝐵
1+( ) 𝑔𝐶,𝐵− 10-50
𝐵𝐵,0
1 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
𝐻2− (𝑆) = ; 𝐻2+ (𝑆) = 1 − 𝐻2− (𝑆)
𝑆 𝑛𝑆,𝐵 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
1+( )
𝑆𝐵,0 𝑛𝐵,𝐵 , 𝑛𝑆,𝐵 , 𝑛𝐵,𝐶 , 1-6
1
𝐻3− (𝐵) = 𝑛𝐶,𝐵
𝐵 𝑛𝐵,𝐶 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 , From half-
1+( )
𝐵𝐶,0
𝐵𝐵,0 , 𝑆𝐵,0 , 𝐵𝐶,0 , functional
1
𝐻 − (𝐶) = ; 𝐻 + (𝐶) = 1 − 𝐻 − (𝐵) 𝐶𝐵,0 rule
𝐶 𝑛𝐶,𝐵
1+( )
𝐶𝐵,0

36
Network
Dynamical Equations Parameter Ranges
Topology
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵) − 𝑘𝐴 . 𝐴
𝑑𝑡 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+𝐵−
𝑑𝐵
= 𝐺𝐵 (𝑆, 𝐴, 𝐵, 𝐶) − 𝑘𝐵 . 𝐵 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆−𝐵+
𝑑𝑡
𝑑𝐶 𝑔𝐴,𝑆− 𝐵− > 𝑔𝐴,𝑆+𝐵+
= 𝑔𝐶,0 + 𝑔𝐶,𝐵+ . 𝐻3+ (𝐵) − 𝑘𝐶 . 𝐶 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶−
𝑑𝑡
𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− > 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶−
𝐺𝐴 (𝑆, 𝐵) = 𝑔𝐴,𝑆− 𝐵− . 𝐻1− (𝑆). 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵− . 𝐻1+ (𝑆). 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶+
+ 𝑔𝐴,𝑆− 𝐵+ . 𝐻1− (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵+ . 𝐻1+ (𝑆). 𝐻1+ (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆− 𝐴+𝐵+ 𝐶−
𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶−
𝐺𝐵 (𝑆, 𝐴, 𝐵, 𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶+
= 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶+
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− < 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆− 𝐴+𝐵− 𝐶− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶−
+ 𝑔𝐵,𝑆− 𝐴−𝐵+ 𝐶− . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶+
+ 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆− 𝐴+ 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆− 𝐴+𝐵+ 𝐶− . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− = 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶+
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶− . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶) 𝑔𝐶,0 < 𝑔𝐶,𝐵+
+ 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶)
𝑔𝐴,𝑆− 𝐵− 1-10
+ 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶+ . 𝐻2− (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶− . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 − (𝐶) 𝑔𝐴,𝑆+ 𝐵− 0.1-1
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵− 𝐶+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2− (𝐵). 𝐻 + (𝐶) 𝑔𝐴,𝑆− 𝐵+ 0.1-1
+ 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶+ . 𝐻2+ (𝑆). 𝐻 − (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶)
𝑔𝐴,𝑆+ 𝐵+ 0.1-1
+ 𝑔𝐵,𝑆− 𝐴+ 𝐵+ 𝐶+ . 𝐻2− (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶)
+ 𝑔𝐵,𝑆+ 𝐴+ 𝐵+ 𝐶+ . 𝐻2+ (𝑆). 𝐻 + (𝐴). 𝐻2+ (𝐵). 𝐻 + (𝐶) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶− 1-10
𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶− 10-50
1
𝐻1− (𝑆) = ; 𝐻1+ (𝑆) = 1 − 𝐻1− (𝑆) 𝑔𝐵,𝑆− 𝐴+ 𝐵− 𝐶− 0.1-1
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶− 10-50
1
𝐻1− (𝐵) = ; 𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵) 𝑔𝐵,𝑆− 𝐴− 𝐵− 𝐶+ 10-50
𝐵 𝑛𝐵,𝐴
1+( )
𝐵𝐴,0 𝑔𝐵,𝑆+ 𝐴− 𝐵+ 𝐶− 10-50
1
𝐻 − (𝐴) = ; 𝐻 + (𝐴) = 1 − 𝐻 − (𝐴) 𝑔𝐵,𝑆+ 𝐴− 𝐵− 𝐶+ 10-50
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0 𝑔𝐵,𝑆− 𝐴− 𝐵+ 𝐶+ 10-50
1
𝐻2− (𝐵) = ; 𝐻2+ (𝐵) = 1 − 𝐻2− (𝐵) 𝑔𝐶,0 1-10
𝐵 𝑛𝐵,𝐵
1+( )
𝐵𝐵,0 𝑔𝐶,𝐵+ 10-50
1
𝐻2− (𝑆) = ; 𝐻2+ (𝑆) = 1 − 𝐻2− (𝑆) 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
𝑆 𝑛𝑆,𝐵
1+( ) 𝑛𝑆,𝐴 , 𝑛𝐵,𝐴 , 𝑛𝐴,𝐵 ,
𝑆𝐵,0
1 𝑛𝐵,𝐵 , 𝑛𝑆,𝐵 , 𝑛𝐵,𝐶 , 1-6
𝐻3− (𝐵) = ; 𝐻3+ (𝐵) = 1 − 𝐻3− (𝐵) 𝑛𝐶,𝐵
𝐵 𝑛𝐵,𝐶
1+( ) From
𝐵𝐶,0 𝑆𝐴,0 , 𝐵𝐴,0 , 𝐴𝐵,0 ,
1 half-
𝐻 − (𝐶) = ; 𝐻 + (𝐶) = 1 − 𝐻 − (𝐵) 𝐵𝐵,0 , 𝑆𝐵,0 , 𝐵𝐶,0 ,
𝐶 𝑛𝐶,𝐵 functional
1+( ) 𝐶𝐵,0
𝐶𝐵,0 rule

37
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐵+ . 𝐻1+ (𝐵) − 𝑘𝐶 . 𝐶
𝑑𝑡 𝑔𝐶,0 < 𝑔𝐶,𝐵+
𝑑𝐴
= 𝐺𝐴 (𝑆, 𝐵, 𝐶) − 𝑘𝐴 . 𝐴 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆+ 𝐵− 𝐶−
𝑑𝑡

𝑑𝐵 𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵+ 𝐶−

= 𝑔𝐵,0 + 𝑔𝐵,𝐴− . 𝐻− (𝐴) − 𝑘𝐵 . 𝐵
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵− 𝐶+
𝐺𝐴 (𝑆, 𝐵, 𝐶)
= 𝑔𝐴,𝑆− 𝐵− 𝐶− . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻2− (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶− . 𝐻 + (𝑆). 𝐻− (𝐵). 𝐻2− (𝐶)
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶− . 𝐻 − (𝑆). 𝐻+ (𝐵). 𝐻2− (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵− 𝐶+
+ 𝑔𝐴,𝑆− 𝐵− 𝐶+ . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻2+ (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶− . 𝐻 + (𝑆). 𝐻+ (𝐵). 𝐻2− (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶+ . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻2+ (𝐶)
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶+ . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻2+ (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻2+ (𝐶)
𝑔𝐵,0 < 𝑔𝐵,𝐴−
1
𝐻1− (𝐵) =
𝐵 𝑛𝐵,𝐶 𝑔𝐶,0 1-10
1+( )
𝐵𝐶,0
𝑔𝐶,𝐵+ 10-50
𝐻1+ (𝐵) =1− 𝐻1− (𝐵)
𝑔𝐴,𝑆− 𝐵− 𝐶− 1-10
1
𝐻 − (𝑆) = 𝑔𝐴,𝑆+ 𝐵− 𝐶− 10-50
𝑆 𝑛𝑆,𝐴
1+( )
𝑆𝐴,0 𝑔𝐴,𝑆− 𝐵+ 𝐶− 0.1-1

𝐻 + (𝑆) = 1 − 𝐻 − (𝑆) 𝑔𝐴,𝑆− 𝐵− 𝐶+ 0.1-1

1 𝑔𝐴,𝑆+ 𝐵+ 𝐶− 𝑔𝐴,𝑆− 𝐵− 𝐶−
𝐻 − (𝐴) =
𝐴 𝑛𝐴,𝐵 𝑔𝐴,𝑆+ 𝐵− 𝐶+ 𝑔𝐴,𝑆− 𝐵− 𝐶−
1+( )
𝐴𝐵,0
𝑔𝐴,𝑆− 𝐵+ 𝐶+ 0.1-1
𝐻 + (𝐴) = 1 − 𝐻 − (𝐴)
𝑔𝐴,𝑆+ 𝐵+ 𝐶+ 𝑔𝐴,𝑆− 𝐵− 𝐶−
1
𝐻2− (𝐶) = 𝑔𝐵,0 1-10
𝐶 𝑛𝐶,𝐴
1+( )
𝐶𝐴,0 𝑔𝐵,𝐴− 10-50

𝐻2+ (𝐶) = 1 − 𝐻2− (𝐶) 𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1

1 𝑛𝐶,𝐴 , 𝑛𝑆,𝐴 , 𝑛𝐴,𝐵

1-6
𝐻 − (𝐵) = 𝑛𝐵,𝐴 , 𝑛𝐵,𝐶 ,
𝐵 𝑛𝐵,𝐴
1+( ) From
𝐵𝐴,0
𝑆𝐴,0 , 𝐶𝐴,0 , 𝐴𝐵,0 , half-
𝐵𝐴,0 , 𝐵𝐶,0 functional
𝐻 + (𝐵) = 1 − 𝐻− (𝐵)
rule

38
Network Topology Dynamical Equations Parameter Ranges
𝑑𝐶
= 𝑔𝐶,0 + 𝑔𝐶,𝐵− . 𝐻1− (𝐵) − 𝑘𝐶 . 𝐶 𝑔𝐶,0 < 𝑔𝐶,𝐵−
𝑑𝑡

𝑑𝐴 𝑔𝐴,𝑆− 𝐵− 𝐶− < 𝑔𝐴,𝑆+ 𝐵− 𝐶−

= 𝐺𝐴 (𝑆, 𝐵, 𝐶) − 𝑘𝐴 . 𝐴
𝑑𝑡
𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵+ 𝐶−
𝑑𝐵
= 𝑔𝐵,0 + 𝑔𝐵,𝐴− . 𝐻− (𝐴) − 𝑘𝐵 . 𝐵
𝑑𝑡 𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵− 𝐶+
𝐺𝐴 (𝑆, 𝐵, 𝐶)
= 𝑔𝐴,𝑆− 𝐵− 𝐶− . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻2− (𝐶) 𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶−
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶− . 𝐻 + (𝑆). 𝐻− (𝐵). 𝐻2− (𝐶)
𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵− 𝐶+
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶− . 𝐻 − (𝑆). 𝐻+ (𝐵). 𝐻2− (𝐶)
+ 𝑔𝐴,𝑆− 𝐵− 𝐶+ . 𝐻 − (𝑆). 𝐻 − (𝐵). 𝐻2+ (𝐶)
𝑔𝐴,𝑆− 𝐵− 𝐶− > 𝑔𝐴,𝑆− 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶− . 𝐻 + (𝑆). 𝐻+ (𝐵). 𝐻2− (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵− 𝐶+ . 𝐻 + (𝑆). 𝐻 − (𝐵). 𝐻2+ (𝐶)
𝑔𝐴,𝑆− 𝐵− 𝐶− = 𝑔𝐴,𝑆+ 𝐵+ 𝐶+
+ 𝑔𝐴,𝑆− 𝐵+ 𝐶+ . 𝐻 − (𝑆). 𝐻 + (𝐵). 𝐻2+ (𝐶)
+ 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ . 𝐻 + (𝑆). 𝐻 + (𝐵). 𝐻2+ (𝐶) 𝑔𝐵,0 < 𝑔𝐵,𝐴−
1
𝐻1− (𝐵) = 𝑔𝐶,0 1-10
𝐵 𝑛𝐵,𝐶
1+( )
𝐵𝐶,0
𝑔𝐶,𝐵− 10-50
𝐻1+ (𝐵) = 1 − 𝐻1− (𝐵) 𝑔𝐴,𝑆− 𝐵− 𝐶− 1-10

1 𝑔𝐴,𝑆+ 𝐵− 𝐶− 10-50
𝐻 − (𝑆) =
𝑆 𝑛𝑆,𝐴
1+( ) 𝑔𝐴,𝑆− 𝐵+ 𝐶− 0.1-1
𝑆𝐴,0
𝑔𝐴,𝑆− 𝐵− 𝐶+ 0.1-1
𝐻 + (𝑆) = 1 − 𝐻 − (𝑆)
𝑔𝐴,𝑆+ 𝐵+ 𝐶− 𝑔𝐴,𝑆− 𝐵− 𝐶−
1
𝐻 − (𝐴) = 𝑔𝐴,𝑆+ 𝐵− 𝐶+ 𝑔𝐴,𝑆− 𝐵− 𝐶−
𝐴 𝑛𝐴,𝐵
1+( )
𝐴𝐵,0
𝑔𝐴,𝑆− 𝐵+ 𝐶+ 0.1-1
𝐻 + (𝐴) = 1 − 𝐻 − (𝐴) 𝑔𝐴,𝑆+ 𝐵+ 𝐶+ 𝑔𝐴,𝑆− 𝐵− 𝐶−
1 𝑔𝐵,0 1-10
𝐻2− (𝐶) =
𝐶 𝑛𝐶,𝐴
1+( ) 𝑔𝐵,𝐴− 10-50
𝐶𝐴,0
𝑘𝐴 , 𝑘𝐵 , 𝑘𝐶 0.01-0.1
𝐻2+ (𝐶) = 1 − 𝐻2− (𝐶)
𝑛𝐶,𝐴 , 𝑛𝑆,𝐴 , 𝑛𝐴,𝐵
1 1-6
𝑛𝐵,𝐴 , 𝑛𝐵,𝐶 ,
𝐻 − (𝐵) =
𝐵 𝑛𝐵,𝐴 From
1+( )
𝐵𝐴,0 𝑆𝐴,0 , 𝐶𝐴,0 , 𝐴𝐵,0 , half-
𝐵𝐴,0 , 𝐵𝐶,0 functional
𝐻 + (𝐵) = 1 − 𝐻− (𝐵) rule

39
S2 Table: The parameter values corresponding to four types of tristable bifurcations for the DNFL-B
network.

Values Values
Parameters Type Type Type Type Parameters Type Type Type Type
I II III IV I II III IV
𝑔𝐴,0 4.0 4.0 4.0 4.0 𝐵𝐴,0 370 335 350 300

𝑔𝐴,𝑆 18.0 18.0 18.0 18.0 𝐴𝐵,0 130 130 130 130

𝑔𝐴,𝐵 0.7 0.7 0.7 0.7 𝐵𝐵,0 67 67 75 75

𝑔𝐴,𝐵,𝑆 4.0 4.0 4.0 4.0 𝑛𝑆,𝐴 2.0 2.0 2.0 2.0

𝑔𝐵,0 7.5 7.5 7.5 7.5 𝑛𝐵,𝐴 6.0 6.0 4.0 4.0

𝑔𝐵,𝐵 39 39 39 39 𝑛𝐴,𝐵 5.0 5.0 5.0 5.0

𝑔𝐵,𝐴 1.0 1.0 1.0 1.0 𝑛𝐵,𝐵 4.0 4.0 6.0 6.0

𝑔𝐵,𝐴𝐵 7.5 7.5 7.5 7.5 𝑘𝐴 0.05 0.05 0.05 0.05

𝑆𝐴,0 140 140 140 140 𝑘𝐵 0.075 0.075 0.075 0.075

40
S3 Table: Examples of the core regulatory networks involving self-activation mutual inhibition motif.

Regulatory
Sl.
Core Regulatory Network Systems and References
No
Phenotypes
Homogeneous
differentiation of
CD4+ T cells.

Phenotypes: High 2-8

1
TH1-Low TH17,
Low TH1-High
TH17 and
Intermediate levels
of TH1, TH17

Homogeneous
differentiation of
CD4+ T cells.
2-8
2 Phenotypes: High
TH1-Low TH2, Low
TH1-High TH2 and
Intermediate levels
of TH1, TH2

Homogeneous
differentiation of
CD4+ T cells.

Phenotypes: High 2-8

3
iTreg-Low TH17,
Low iTreg-High
TH17 and
Intermediate levels
of iTreg, TH17

Transcriptional
regulations among
four core factors
controlling the
early T-cell 9-14
4
development

Phenotype:
ETP/DN1, DN2a,
DN2b, DN3

Epithelial to
mesenchymal
transitions

Phenotypes: 15-19
5
Epithelia (E),
Mixed Epithelial-
Mesenchymal
(E/M),
Mesenchymal (M)

41
 Pluripotency in
embryonic stem
cells
20-22
6
Phenotypes: Epi
like state, ICM like
state, PrE like
state
Thymus
differentiation of
23, 24
7 Th1 and Th2

Regulatory
network of the
Candida Albicans
24
8
Phenotypes: White
states, Opaque
states and mixed
states
Differentiation of a
common myeloid
progenitor into 25-28
9
erythrocyte and
macrophage

Differentiation of
embryonic stem
29, 30
10 cells by reciprocal
inhibition of their
target genes
Amoeboid to
mesenchymal
transitions
31-34
11 Phenotypes:
Amoeboid,
mesenchymal,
amoeboid/mesenc
hymal hybrid
Differentiation of
multipotent
pancreatic
progenitors. 35, 36
12
Phenotypes:
Ductal/endocrine,
Acinar

42
MATLAB codes to the 2-C DNFL-B network to run the 1-p bifurcation analysis
%**************************************************************************
% Title: Potential landscapes, bifurcations and robustness of tristable
networks
% Authors: Anupam Dey & Debashis Barik
% School of Chemistry, University of Hyderabad, India
% Email: dbariksc@uohyd.ac.in
%**************************************************************************
%**************************************************************************
% Threshold calculations for 2-C DNFL_B motif
%**************************************************************************

% Isoalted A,B,S

clear
clc

nr=1000000; % number of SSs

% synthesis rates for A,B and S

ga0=1+(10-1)*rand(nr,1);
gb0=1+(10-1)*rand(nr,1);
gs0=1+(10-1)*rand(nr,1);

% degradation rates for A,B and S

ka=0.01+(0.1-0.01)*rand(nr,1);
kb=0.01+(0.1-0.01)*rand(nr,1);
ks=0.01+(0.1-0.01)*rand(nr,1);

% SS equations for A,B and S

aa_iso=ga0./ka;
bb_iso=gb0./kb;
ss_iso=gs0./ks;

% Conversion of the SSs into log2 scale

aisoLog=log2(aa_iso);
bisoLog=log2(bb_iso);
sisoLog=log2(ss_iso);

% Truncating the SS distribution

athreLog=aisoLog(aisoLog>0.02*median(aisoLog) &
aisoLog<1.98*median(aisoLog));
bthreLog=bisoLog(bisoLog>0.02*median(bisoLog) &
bisoLog<1.98*median(bisoLog));
sthreLog=sisoLog(sisoLog>0.02*median(sisoLog) &
sisoLog<1.98*median(sisoLog));

% Reconverting the SSs into linear scale

athre_iso=2.^athreLog;
bthre_iso=2.^bthreLog;
sthre_iso=2.^sthreLog;

figure(1)
subplot(2,2,1)
hist(aisoLog,100)
hold on
hist(athreLog,100)
subplot(2,2,2)

43
hist(bisoLog,100)
hold on
hist(bthreLog,100)

subplot(2,2,3)
hist(sisoLog,100)
hold on
hist(sthreLog,100)

save -ascii threS_in_dnflb.dat sthre_iso

% Inward interactions to A
nr1=min([length(athre_iso) length(bthre_iso) length(sthre_iso)]);

ga0=1+(10-1)*rand(nr1,1);
gas=10+(50-10)*rand(nr1,1);
gab=0.1+(1-0.1)*rand(nr1,1);
gabs=ga0;
nsa=randi([1 6],nr1,1);
nba=randi([1 6],nr1,1);
ka=0.01+(0.1-0.01)*rand(nr,1);

hsm=1./(1+(ss_iso./sthre_iso).^nsa);
hsp=1-hsm;
h1bm=1./(1+(bb_iso./bthre_iso).^nba);
h1bp=1-h1bm;

gasb=ga0.*hsm.*h1bm+gas.*hsp.*h1bm+gab.*hsm.*h1bp+gabs.*hsp.*h1bp;

aa_in=gasb./ka; % SS equation of A

ainLog=log2(aa_in);

athreLog_in=ainLog(ainLog>0.02*median(ainLog) &
ainLog<1.98*median(ainLog));

athre_in=2.^athreLog_in;

figure(2)
subplot(2,1,1)
hist(ainLog,100)
hold on
hist(athreLog_in,100)

save -ascii threA_in_dnflb.dat athre_in

% Inward interactions to B

gb0=1+(10-1)*rand(nr1,1);
gba=0.1+(1-0.1)*rand(nr1,1);
gbb=10+(50-10)*rand(nr1,1);
gbba=gb0;
nbb=randi([1 6],nr1,1);
nab=randi([1 6],nr1,1);
kb=0.01+(0.1-0.01)*rand(nr,1);

h2bm=1./(1+(bb_iso./bthre_iso).^nbb);
h2bp=1-h2bm;

44
ham=1./(1+(aa_iso./athre_iso).^nab);
hap=1-ham;

gbab=gb0.*ham.*h2bm+gba.*hap.*h2bm+gbb.*ham.*h2bp+gbba.*hap.*h2bp;

bb_in=gbab./kb; % SS equation of B

binLog=log2(bb_in);

bthreLog_in=binLog(binLog>0.02*median(binLog) &
binLog<1.98*median(binLog));

bthre_in=2.^bthreLog_in;

figure(2)
subplot(2,1,2)
hist(binLog,100)
hold on
hist(bthreLog_in,100)

save -ascii threB_in_dnflb.dat bthre_in

45
%**************************************************************************
% Title: Potential landscapes, bifurcations and robustness of tristable
networks
% Authors: Anupam Dey & Debashis Barik
% School of Chemistry, University of Hyderabad, India
% Email: dbariksc@uohyd.ac.in
%**************************************************************************

%**************************************************************************
% Bifurcation analysis of DNFL-B network
%**************************************************************************

clear
clc
tic

% loading threshold values calculated using half-functional rule

% Needed to be calculated separately
load threS_in_dnflb.dat
load threA_in_dnflb.dat
load threB_in_dnflb.dat

% counter for bifurcation types

Type1=0;
Type2=0;
Type3=0;
Type4=0;

% no. of parameter combinations

nr=500000;

sizeS=length(threS_in_dnflb);
sizeA=length(threA_in_dnflb);
sizeB=length(threB_in_dnflb);

rndS=randperm(sizeS)';
rndA=randperm(sizeA)';
rndB1=randperm(sizeB)';
rndB2=randperm(sizeB)';

% Parameters are chosen from uniform distribution

ga0=1+(10-1).*rand(1,nr)';
gas=10+(50-10).*rand(1,nr)';
gab=0.1+(1-0.1).*rand(1,nr)';
gabs=ga0;
gb0=1+(10-1).*rand(1,nr)';
gbb=10+(50-10).*rand(1,nr)';
gba=0.1+(1-0.1).*rand(1,nr)';
gbab=gb0;
sa0=threS_in_dnflb(rndS(1:nr));
ba0=threB_in_dnflb(rndB1(1:nr));
ab0=threA_in_dnflb(rndA(1:nr));
bb0=threB_in_dnflb(rndB2(1:nr));
nsa=randi([1,6],1,nr)';
nba=randi([1,6],1,nr)';
nab=randi([1,6],1,nr)';
nbb=randi([1,6],1,nr)';
ka=0.01+(0.1-0.01).*rand(1,nr)';
kb=0.01+(0.1-0.01).*rand(1,nr)';

46
NN1=100;
NN2=10000;
del1=10;
del2=0.1;
int1=0.1;
int2=0.1;
intf=1500;

% storing parameter values

data=[ga0 gas gab gabs gb0 gbb gba gbab sa0 ba0 ab0 bb0 nsa nba ...
nab nbb ka kb];
nmbr_peaks_ss=[];
nmbr_peaks_us=[];
tri_par=[];
bfd=[];
yx=[];

ic1=0;

for kk=1:nr % loop for parameters

kk;

% *********************************************************************
% Finding no. of stable and unstable steady states with variation of
% bifurcation parameter. Stable and unstable steady states are given
% by minima and maxima in the potential function (PF), respectively.
% *********************************************************************
% The jj loop below is a run of parameter search with bigger step size
% of the bifurcation parameter. It picks up a parameter combination
% haiving 3 stable steady states.
% *********************************************************************
for jj=1:NN1 % loop for bifurcation parameter
ik(jj)=jj.*del1;

b1=[0:int1:intf]; % range for argument in potential function

hsm = 1./(1+((ik(jj))/sa0(kk)).^nsa(kk));

hsp = 1-hsm;

h1bm = 1./(1+(b1./ba0(kk)).^nba(kk));

h1bp = 1-h1bm;

gasb = ga0(kk).*hsm.*h1bm+gas(kk).*hsp.*h1bm+ ...

gab(kk).*hsm.*h1bp+gabs(kk).*hsp.*h1bp;

a1 = gasb./ka(kk);

ham = 1./(1+(a1./ab0(kk)).^nab(kk));

hap = 1-ham;

h2bm = 1./(1+(b1./bb0(kk)).^nbb(kk));

h2bp = 1-h2bm;

47
 gbba = gb0(kk).*h2bm.*ham+gbb(kk).*h2bp.*ham+ ...
gba(kk).*h2bm.*hap+gbab(kk).*h2bp.*hap;

f = gbba-kb(kk).*b1;

% z: potential function obatined by integration of the force (f)

z=cumtrapz(-f);

% rescaling of potential against the global minima of the

pontential function
z1=z-min(z);

z2=-z1;

nmbr_peaks_ss(jj)=numel(findpeaks(z2)); % no. of minima in the

PF
nmbr_peaks_us(jj)=numel(findpeaks(z1)); % no. of maxima in the
PF

end
% *********************************************************************
% End of finding no. of steady states calculation
% *********************************************************************

% *********************************************************************
% Calculation of bifurcation diagram for the parameter combination that
% generates more than one stable steady states(only for multistability)
% *********************************************************************

% Counting the no. of stable steady state

if (nmbr_peaks_ss(1)>1) % represents irreversible switch
continue
elseif (nmbr_peaks_us(end)>=1) % beyond the range of bifurcation
parameter
continue
elseif (nmbr_peaks_us(1)>=1) % represents irreversible switch
continue
elseif (nmbr_peaks_ss(end)>1) % beyond the range of bifurcation
parameter
continue
elseif any(nmbr_peaks_ss==3) % for tristability

ic1=ic1+1;
tri_par(ic1)=kk; % index for the parameter combination
kk % that results tristability

bfd=ones(NN2,6)*NaN;

% Loop for actual bifurcation analysis with smaller step size in

% the bifurcation parameter
for j=1:NN2
n(j)=j*del2;

b2=[0:int1:intf];

hsm = 1./(1+((n(j))./sa0(kk)).^nsa(kk));

hsp = 1-hsm;

48
 h1bm = 1./(1+(b2./ba0(kk)).^nba(kk));

h1bp = 1-h1bm;

gasb = ga0(kk).*hsm.*h1bm+gas(kk).*hsp.*h1bm+ ...

gab(kk).*hsm.*h1bp+gabs(kk).*hsp.*h1bp;

a2 = gasb./ka(kk);

ham = 1./(1+(a2./ab0(kk)).^nab(kk));

hap = 1-ham;

h2bm = 1./(1+(b2./bb0(kk)).^nbb(kk));

h2bp = 1-h2bm;

gbba = gb0(kk).*h2bm.*ham+gbb(kk).*h2bp.*ham+ ...

gba(kk).*h2bm.*hap+gbab(kk).*h2bp.*hap;

f = gbba-kb(kk).*b2;

z=cumtrapz(-f);
z1=z-min(z);
z2=z1*-1;

[pks_stb locs_stb] = findpeaks(z2); % pks_stb: no. of stable ss

rz_stb=repmat(n(j),size(locs_stb)); % locs_stb: location of
stable ss
dz_stb=[rz_stb;locs_stb.*int2]'; % storing the coordinates
of
% the stable ss.

% rearranging the data for stable manifold

bfd(j,1)=n(j);
if(size(dz_stb,1)==3)
bfd(j,2)=dz_stb(1,2);
bfd(j,3)=NaN;
bfd(j,4)=dz_stb(2,2);
bfd(j,5)=NaN;
bfd(j,6)=dz_stb(3,2);
elseif(size(dz_stb,1)==2)
bfd(j,2)=dz_stb(1,2);
bfd(j,3)=NaN;
bfd(j,4)=dz_stb(2,2);
bfd(j,5)=NaN;
bfd(j,6)=NaN;
elseif(size(dz_stb,1)==1)
bfd(j,2)=dz_stb(1,2);
bfd(j,3)=NaN;
bfd(j,4)=NaN;
bfd(j,5)=NaN;
bfd(j,6)=NaN;
else
bfd(j,2)=NaN;
bfd(j,3)=NaN;
bfd(j,4)=NaN;
bfd(j,5)=NaN;

49
 bfd(j,6)=NaN;
end

[pks_us locs_us] = findpeaks(z1); % pks_stb: no. of unstable

ss
rz_us=repmat(n(j),size(locs_us)); % locs_stb: location of
unstable ss
dz_us=[rz_us;locs_us.*int2]'; % storing the coordinates
of
% unstable ss.
if(size(pks_us,2)==2)
bfd(j,3)=dz_us(1,2);
bfd(j,5)=dz_us(2,2);
elseif (size(pks_us,2)==1)
bfd(j,3)=dz_us(1,2);
bfd(j,5)=NaN;
end
end

yx=[bfd(:,1) bfd(:,2)
bfd(:,1) bfd(:,3)
bfd(:,1) bfd(:,4)
bfd(:,1) bfd(:,5)
bfd(:,1) bfd(:,6)];
[~,idx1] = sort(yx(:,2));
bdia = yx(idx1,:);

bfr=bdia(bdia(:,2)>0);
steady=(bdia(1:size(bfr,1),:));

unsta=[bfd(:,1) bfd(:,3)
bfd(:,1) bfd(:,5)];
[~,idx2] = sort(unsta(:,2));
yy1 = unsta(idx2,:);

% plot of bifurcation diagram (only for multistability)

figure(1)
plot(bdia(:,1),bdia(:,2))
hold on
plot(yy1(:,1),yy1(:,2),'.')
hold on

% finding the saddle-node (SN) bifurcation point

yz=yy1(yy1(:,2)>0);
yz1=(yy1(1:size(yz,1),:));

x1=yz(1);
y1=yz1(1,2);
x4=yz(end);
y4=yz1(end,2);

diffr=diff(yz1(:,2));

[~,ind]=max(diffr);
x2=yz1(ind,1);
y2=yz1(ind,2);

x3=yz1(ind+1,1);
y3=yz1(ind+1,2);

50
yx1=yx(:,2);
yx2=yx1(yx1>0);

maxst=max(steady(:,1));
index_maxst=find(steady(:,1)==maxst);
yvalmax=steady(index_maxst,2);

minst=min(steady(:,1));
index_minst=find(steady(:,1)==minst);
yvalmin=steady(index_minst,2);

maxy=max(steady(:,2));
index_maxy=find(steady(:,2)==maxy);
xvalmaxy=steady(index_maxy(1),1);

miny=min(steady(:,2));
index_miny=find(steady(:,2)==miny);
xvalminy=steady(index_miny(1),1);

% assignment of SN points
if (xvalmaxy<xvalminy)
sn1=x4;
ybp1=y4;
sn4=x1;
ybp4=y1;
sn3=x2;
ybp3=y2;
sn2=x3;
ybp2=y3;
elseif (xvalmaxy>xvalminy)
sn4=x4;
ybp4=y4;
sn1=x1;
ybp1=y1;
sn2=x2;
ybp2=y2;
sn3=x3;
ybp3=y3;
end

if (sn2==sn4)
sn4=sn4+(-del2+(del2+del2).*rand(1));
end

if (sn1==sn3)
sn3=sn3+(-del2+(del2+del2).*rand(1));
end

if (sn2>sn3)
sn2=NaN;
sn3=NaN;
y2=NaN;
y3=NaN;
end

% storing SN points
bp1=[sn1 ybp1];
bp2=[sn2 ybp2];

51
 bp3=[sn3 ybp3];
bp4=[sn4 ybp4];
bifr_pts=[bp1; bp2; bp3; bp4];

% determination of type of bifurcation in tistability

if (sn1>sn3) && (sn3>sn2) && (sn2>sn4)
Type4=Type4+1;
disp('Type4')
bifur_type(ic1)=4;
figure(2)
subplot(2,2,4)
plot(bdia(:,1),bdia(:,2),'.')
hold on
scatter(yy1(:,1),yy1(:,2),'black.')
hold on
title('Type 4')

elseif (sn3>sn1) && (sn1>sn2) && (sn2>sn4)

Type3=Type3+1;
disp('Type3')
bifur_type(ic1)=3;
figure(2)
subplot(2,2,3)
plot(bdia(:,1),bdia(:,2),'.')
hold on
scatter(yy1(:,1),yy1(:,2),'black.')
hold on
title('Type 3')

elseif (sn1>sn3) && (sn3>sn4) && (sn4>sn2)

Type2=Type2+1;
disp('Type2')
bifur_type(ic1)=2;
figure(2)
subplot(2,2,2)
plot(bdia(:,1),bdia(:,2),'.')
hold on
scatter(yy1(:,1),yy1(:,2),'black.')
hold on
title('Type 2')

elseif (sn3>sn1) && (sn1>sn4) && (sn1>sn2)

Type1=Type1+1;
disp('Type1')
bifur_type(ic1)=1;
figure(2)
subplot(2,2,1)
plot(bdia(:,1),bdia(:,2),'.')
hold on
scatter(yy1(:,1),yy1(:,2),'black.')
hold on
title('Type 1')

end

% plot(bp1(:,1),bp1(:,2),'r*')
% plot(bp2(:,1),bp2(:,2),'b*')
% plot(bp3(:,1),bp3(:,2),'g*')
% plot(bp4(:,1),bp4(:,2),'magenta*')
% hold on

52
 end

end

Type1
Type2
Type3
Type4

Tot=Type1+Type2+Type3+Type4

result=[Type1 Type2 Type3 Type4]

data_param=data(tri_par,:)';
% saving parameter corresponding to tristable bifurcation
save -ascii data_param_dnflb.dat data_param
% saving counts of tistable types
save -ascii res_dnflb.dat result
% saving tristable bifurcation type identifier for the parameter
combination
save -ascii bifur_type_dnflb.dat bifur_type

toc

53
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