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Table 2 Biological interpretation based on literature and assignment of each process in Figure 6

From: Simulation-based model checking approach to cell fate specification during Caenorhabditis elegans vulval development by hybrid functional Petri net with extension

Wet experiments results published in literature

#1

#2

Reaction type

Refs

Translocation of LIN-3 emanated from AC to P5.p and P7.p

p 1

LSMass(m1*0.1*low, 0.1)

Translocation

[9, 35]

Translocation of LIN-3 emanated from AC to P3.p, P4.p and P8.p

p 2

LSMass(m1*0.1*mid, 0.1)

Translocation

[9, 35]

ligands LIN-3 binding to LET-23 to form a ligand-receptor complex

p 3

LSMass(m1*0.1*high, 0.1)

Binding

[43, 44]

Two identical LIN-3 LET-23 complex combining to form a dimer

p 4

LSMass(m3*0.1, 0.5)

Dimerization

[43, 44]

Autophosphorylation following the dimerization of ligand-receptor complex

p 5

LSMass(m4*0.1, 0.5)

Autophosphorylation

[43, 44]

SEM-5 is activated by LIN-3 LET-23 dimer

p 6

LSMass(m5*m6*0.1, 0.5)

Enzymic reaction

[9, 35]

LET-60 is activated by upstream SEM-5

p 7

LSMass(m7*m8*0.1, 0.5)

Enzymic reaction

[9, 35]

Inactive MPK-1 is activated by upstream LET-60

p 8

LSMass(m9*m10*0.1, 0.5)

Enzymic reaction

[9, 35]

The movement of MPK-1 from cytoplasm to nucleus

p 9

LSMass(m11*0.1, 0.5)

Translocation

-

Active MPK-1(N) downregulates the target genes of lst and transcribes the mRNA of lateral signal (LS)

p 10

LSMass(m12*0.1, 0.5)

Transcription

[9]

LS mRNA is translated to LS molecules

p 11

LSMass(m17*0.1, 0.5)

Translation

-

Translated LS molecules are released to combine with

p 12

LSMass(m19*0.1, 0.5)

Translocation

[34]

LIN-12 receptors

    

LIN-31/LIN-1 complex is dissociated to individual active

p 13

LSMass(m12*m13*0.1, 0.5)

Phosphorylation

[38, 45]

LIN-31 and LIN-1 by the phosphorylation of active MPK-1

    

Active a MPK-1(N) acts as transcription factor to tran-

p 14

LSMass(m14*0.1, 0.5)

Transcription

[42]

scribe vulval genes to mRNA

    

mRNA of vulval genes is translated and cause the 1

p 15

LSMass(m16*0.1, 0.5)

Translation

[42]

cell fate

    

LIN-12 receptor received the LS molecules from the ad-

p 16

LSMass(m20*m κ *1.0, 0.1)

Binding

[32, 34]

jacent Pn.p and shape a ligand-receptor complex

    

LIN-12 receptor received the LS molecules from its own

p 17

LSMass(m20*m κ *1.0, 0.1)

Binding

[32, 34]

Pn.p and shape a ligand-receptor complex

    

LIN-12 receptor received the LS molecules from the ad-

p 18

LSMass(m20*m κ *0.1, 0.1)

Binding

[32, 34]

jacent Pn.p and shape a ligand-receptor complex

    

Binding of LS ligands to LIN-12/Notch receptor leads to

p 19

LSMass(m21*0.1, 0.5)

Shedding/Cleavage

[34]

shedding of the LIN-12/Notch extracellular domain via cleavage

    

Cleaved intracellular domain of LIN-12/Notch receptor move from cytoplasm to nucleus

p 20

LSMass(m23*0.1, 0.5)

Translocation

[34, 46]

Cleaved LIN-12/Notch receptor promote the target lst genes transcribed into mRNA of lst genes

p 21

LSMass(m24*0.1, 0.5)

Transcription

[34, 36]

LST mRNA is translated to LST in cytoplasm

p 22

LSMass(m26*0.1, 0.5)

Translation

-

LIN-12 immediately induces lst expression thus prevents cells from engaging the mechanisms reducing LIN-12 activity

p 23

LSMass(m20*lin 12_init, 0.1)

Production

[9]

LIN-3 emanating from hyp7 binds to LET-23 to form a complex

p 24

LSMass(m2*m28*0.1, 0.5)

Expression

[9, 37]

  1. Table 2: The column of #1 represents corresponding processes in the HFPNe model. Twenty-four events are assigned to the processes p i ∈ {p1, ⋯, p24}. Each reaction speed of the processes is assigned as shown in the column of #2, in which several reaction speeds have been tuned manually. Reaction types of the processes are described in the fourth column with the literature facts given in the fifth column. Variable m x ∈ {m1, ⋯, m32} denotes the concentration of corresponding substance (see Table 3). The variable mk is used to collectively denote the concentration of the LS molecules generated from the adjacent Pn.p. The values of high, mid, and low are assigned to 100, 1, and 0.01. For example, the process p9 has a reaction speed with a noise denoted by LSMass(m11 *0.1, 0.5), i.e., the reaction speed depends on the concentration of MPK-1{active} (C) in the cytoplasm (m11). LSMass() is a function of log-normal distribution (see text).