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Limit cycles and update schedules in Boolean networks: Inverse - - PowerPoint PPT Presentation

Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem Limit cycles and update schedules in Boolean networks: Inverse Problem. (Results of Luis G omezs Ph.D. Thesis)


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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit cycles and update schedules in Boolean networks: Inverse Problem.

(Results of Luis G´

  • mez’s Ph.D. Thesis)

Advisors: L. Salinas(UdeC), J. Demongeot (UG) and J. Aracena (UdeC).

Novembre 2014

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Summary

1 Definition and Notation 2 Limit Cycle Existence problem 3 Limit Cycle Non Existence problem 4 Feasible Limit Cycle problem

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Boolean Networks

A Boolean network is N = (F, s), where F = (fv)v∈V :: {0, 1}n → {0, 1}n, global transition function, V a set of n elements. fv(x) := F(x)v, ∀v ∈ V , local activation functions. s : V → {1, . . . , n} a deterministic update schedule (parallel,sequential, block-sequential).

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Interaction Digraph

G F = (V , A) interaction digraph associated to a Boolean Network. (u, v) ∈ A if an only if fv depends on xu.

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Interaction Digraph

G F = (V , A) interaction digraph associated to a Boolean Network. (u, v) ∈ A if an only if fv depends on xu.

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Example 1

F : {0, 1}4 → {0, 1}4 f1(x) := x3 ∧ x4 f2(x) := x1 ∧ x3 f3(x) := (x1 ∧ x2) ∨ x4 f4(x) := x2 1 2 3 4

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Example 1

F : {0, 1}4 → {0, 1}4 f1(x) := x3 ∧ x4 f2(x) := x1 ∧ x3 f3(x) := (x1 ∧ x2) ∨ x4 f4(x) := x2 1 2 3 4

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Example 1

F : {0, 1}4 → {0, 1}4 f1(x) := x3 ∧ x4 f2(x) := x1 ∧ x3 f3(x) := (x1 ∧ x2) ∨ x4 f4(x) := x2 1 2 3 4

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Example 1

F : {0, 1}4 → {0, 1}4 f1(x) := x3 ∧ x4 f2(x) := x1 ∧ x3 f3(x) := (x1 ∧ x2) ∨ x4 f4(x) := x2 1 2 3 4

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Example 1

F : {0, 1}4 → {0, 1}4 f1(x) := x3 ∧ x4 f2(x) := x1 ∧ x3 f3(x) := (x1 ∧ x2) ∨ x4 f4(x) := x2 1 2 3 4

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Update Schedule

s : V → {1, . . . , n}, function.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Update Schedule

s : V → {1, . . . , n}, function. s(V ) = {1}, parallel. 1 2 3 4 5

s(1) = 1 s(2) = 1 s(3) = 1 s(4) = 1 s(5) = 1

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Update Schedule

s : V → {1, . . . , n}, function. s(V ) = {1}, parallel. s(V ) = {1, . . . , n}, sequential. 1 2 3 4 5

s(1) = 1 s(2) = 2 s(3) = 3 s(4) = 4 s(5) = 5

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Update Schedule

s : V → {1, . . . , n}, function. s(V ) = {1}, parallel. s(V ) = {1, . . . , n}, sequential. s(V ) = {1, . . . , m}, 1 < m < n, block-sequential. 1 2 3 4 5

s(1) = 1 s(2) = 1 s(3) = 2 s(4) = 3 s(5) = 3

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Iteration

Given x = (xv)v∈V ∈ {0, 1}n, the (k + 1)-iteration of x by F according to s is given by: xk+1

v

= fv(xlu

u : u ∈ V )

Where: lu =

  • k

if s(v) ≤ s(u) k + 1 if s(v) > s(u)

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Iteration

Given x = (xv)v∈V ∈ {0, 1}n, the (k + 1)-iteration of x by F according to s is given by: xk+1

v

= fv(xlu

u : u ∈ V )

Where: lu =

  • k

if s(v) ≤ s(u) k + 1 if s(v) > s(u)

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Dynamical Behavior

We can define f s

v (x) = fv(gs v,u(x): u ∈ V )

Where: gs

v,u(x) =

  • xu

if s(v) ≤ s(u) f s

u (x)

if s(v) > s(u) F s is the dynamical behavior of N = (F, s).

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Dynamical Behavior

We can define f s

v (x) = fv(gs v,u(x): u ∈ V )

Where: gs

v,u(x) =

  • xu

if s(v) ≤ s(u) f s

u (x)

if s(v) > s(u) F s is the dynamical behavior of N = (F, s).

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Dynamical Behavior

We can define f s

v (x) = fv(gs v,u(x): u ∈ V )

Where: gs

v,u(x) =

  • xu

if s(v) ≤ s(u) f s

u (x)

if s(v) > s(u) F s is the dynamical behavior of N = (F, s).

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Behavior

Fixed point: x ∈ {0, 1}n : F s(x) = x Limit Cycles: C =

  • xkp

k=0 , xk ∈ {0, 1}n, p > 1:

xk+1 = F s(xk) ∧ xp ≡ x0 LC(N): set of limit cycles of N.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Behavior

Fixed point: x ∈ {0, 1}n : F s(x) = x Limit Cycles: C =

  • xkp

k=0 , xk ∈ {0, 1}n, p > 1:

xk+1 = F s(xk) ∧ xp ≡ x0 LC(N): set of limit cycles of N.

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Behavior

Fixed point: x ∈ {0, 1}n : F s(x) = x Limit Cycles: C =

  • xkp

k=0 , xk ∈ {0, 1}n, p > 1:

xk+1 = F s(xk) ∧ xp ≡ x0 LC(N): set of limit cycles of N.

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Update Digraph

Given a Boolean network (F, s), we define the associated labeled digraph G F

s = (G F, labs), called update digraph, where labs : A(G F) → {⊖, ⊕} is

defined as: labs(u, v) =

if s(u) ≥ s(v) ⊖ if s(u) < s(v) Example:

1 2 3 4

⊕ ⊖ ⊖ ⊖ ⊕ ⊕

s(i) = i, ∀i ∈ {1, . . . , n}.

It was proven in (Aracena, J., Goles, E., Moreira, A., Salinas, L., 2009. Biosystems 97, 1-8) that if two different updates schedules have the same update digraph, then they also have the same dynamical behavior.

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Update Digraph

Given a Boolean network (F, s), we define the associated labeled digraph G F

s = (G F, labs), called update digraph, where labs : A(G F) → {⊖, ⊕} is

defined as: labs(u, v) =

if s(u) ≥ s(v) ⊖ if s(u) < s(v) Example:

1 2 3 4

⊕ ⊖ ⊖ ⊖ ⊕ ⊕

s(i) = i, ∀i ∈ {1, . . . , n}.

It was proven in (Aracena, J., Goles, E., Moreira, A., Salinas, L., 2009. Biosystems 97, 1-8) that if two different updates schedules have the same update digraph, then they also have the same dynamical behavior.

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Update Digraph

Given a Boolean network (F, s), we define the associated labeled digraph G F

s = (G F, labs), called update digraph, where labs : A(G F) → {⊖, ⊕} is

defined as: labs(u, v) =

if s(u) ≥ s(v) ⊖ if s(u) < s(v) Example:

1 2 3 4

⊕ ⊖ ⊖ ⊖ ⊕ ⊕

s(i) = i, ∀i ∈ {1, . . . , n}.

It was proven in (Aracena, J., Goles, E., Moreira, A., Salinas, L., 2009. Biosystems 97, 1-8) that if two different updates schedules have the same update digraph, then they also have the same dynamical behavior.

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Summary

1 Definition and Notation 2 Limit Cycle Existence problem 3 Limit Cycle Non Existence problem 4 Feasible Limit Cycle problem

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Inverse problems of update schedules

General problem Given F = (fv)v∈V : {0, 1}n → {0, 1}n. Does there exists an update schedule s such that (F, s) has a given dynamical property? Particular cases: Limit Cycle Existence problem (LCE) Limit Cycle Non Existence problem (LCNE) Feasible Limit Cycle (FLC)

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Inverse problems of update schedules

General problem Given F = (fv)v∈V : {0, 1}n → {0, 1}n. Does there exists an update schedule s such that (F, s) has a given dynamical property? Particular cases: Limit Cycle Existence problem (LCE) Limit Cycle Non Existence problem (LCNE) Feasible Limit Cycle (FLC)

Nice 2014 Limit cycles and update schedules in Boolean networks

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Existence problem

Limit Cycle Existence problem (LCE) Given F = (fv)v∈V : {0, 1}n → {0, 1}n. Does there exists an update schedule s such that LC(F, s) = ∅?

Previous works: The specific problem of determining the existence of limit cycles of a Boolean network with parallel update is known to be NP-Hard (Just, W., 2006. The steady state system problem is NP-Hard even for monotone quadratic Boolean dynamical systems. pre-print).

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Existence problem

Limit Cycle Existence problem (LCE) Given F = (fv)v∈V : {0, 1}n → {0, 1}n. Does there exists an update schedule s such that LC(F, s) = ∅?

Previous works: The specific problem of determining the existence of limit cycles of a Boolean network with parallel update is known to be NP-Hard (Just, W., 2006. The steady state system problem is NP-Hard even for monotone quadratic Boolean dynamical systems. pre-print).

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Existence problem

Theorem AND-OR LCE is NP-hard. Proof (idea): SAT ≤p AND-OR LCE.

vφ vC1 vC2 . . . vCm v1 ¯ v1 vn ¯ vn a1

  • 1

. . . an

  • n

A O z1 z2 z3

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Existence problem

Theorem AND-OR LCE is NP-hard. Proof (idea): SAT ≤p AND-OR LCE.

vφ vC1 vC2 . . . vCm v1 ¯ v1 vn ¯ vn a1

  • 1

. . . an

  • n

A O z1 z2 z3

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Existence problem

Remark: AND-OR LCE is NP-Hard even in the following cases: i.- Restricted to the parallel update schedule. ( In this case we remove the vertex z3 and we add an arc from z1 to z2.) ii.- Restricted to sequential update schedules. iii.- Restricted to limit cycles of length 2. iv.- Restricted to maximum in-degree equal to 2.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Existence problem

Theorem SYMMETRIC LCE is NP-Hard. Proof: The proof is similar with the following local activation functions: ∀i ∈ {1, . . . , n},

fvi(x) = xvi ∧ xvφ fvφ(x) = φ (xvi) ∧ (xz1 ∨ xz2) fz1(x) = xvφ ∧ xz2 fz2(x) = xvφ ∧ xz1

vφ v1 v2 vn . . . z1 z2

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Existence problem

Theorem SYMMETRIC LCE is NP-Hard. Proof: The proof is similar with the following local activation functions: ∀i ∈ {1, . . . , n},

fvi(x) = xvi ∧ xvφ fvφ(x) = φ (xvi) ∧ (xz1 ∨ xz2) fz1(x) = xvφ ∧ xz2 fz2(x) = xvφ ∧ xz1

vφ v1 v2 vn . . . z1 z2

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit cycles in symmetric AND-OR networks

Defn: Given F an AND-OR function with symmetric G F. Let G OR

1

, . . . , G OR

kOR be the non trivial connected components of

G [VOR(F)]. Let G AND

1

, . . . , G AND

kAND be the non trivial connected components of

G [VAND(F)]. We define the alternated nodes as VAO = V \ kOR

  • i=1

V

  • G OR

i

kAND

  • i=1

V

  • G AND

i

  • and we denote by G AO

1

, . . . , G AO

kAO, to the connected component of

G [VAO].

  • G OR

1

, . . . , G OR

kOR, G AND 1

, . . . , G AND

kAND , G AO 1

, . . . , G AO

kAO

  • is an AOA

(AND-OR ALTERNATED) decomposition of G F.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycles in AND-OR symmetric networks

Theorem Given F an AND-OR function with symmetric G F. There exists an update schedule s such that, LC(F, s) = ∅ if and only if there exists a bipartite element (without loops) in the AOA decomposition of G F. Corollary SYMMETRIC AND-OR LCE is polynomial. Remark: In AND-OR networks with symmetric G F with block-sequential update there are limit cycles of length super-polynomial.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycles in AND-OR symmetric networks

Theorem Given F an AND-OR function with symmetric G F. There exists an update schedule s such that, LC(F, s) = ∅ if and only if there exists a bipartite element (without loops) in the AOA decomposition of G F. Corollary SYMMETRIC AND-OR LCE is polynomial. Remark: In AND-OR networks with symmetric G F with block-sequential update there are limit cycles of length super-polynomial.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Summary

1 Definition and Notation 2 Limit Cycle Existence problem 3 Limit Cycle Non Existence problem 4 Feasible Limit Cycle problem

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Non Existence problem

Limit Cycle Non Existence problem (LCNE) Given F = (fv)v∈V : {0, 1}n → {0, 1}n. Does there exists an update schedule s such that: LC (F, s) = ∅?

Previous works: Symmetric threshold networks with sequential update schedule: Fogelman, F., Goles, E., , Pellegrin, D., 1985. Decreasing energy functions as a tool for studying threshold networks. Discrete Applied Mathematics 12, 261-277. OR networks: Goles, E., Noual, M., 2012. Disjunctive networks and update schedules. Advances in Applied Mathematics 48, 646-662.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Non Existence problem

Limit Cycle Non Existence problem (LCNE) Given F = (fv)v∈V : {0, 1}n → {0, 1}n. Does there exists an update schedule s such that: LC (F, s) = ∅?

Previous works: Symmetric threshold networks with sequential update schedule: Fogelman, F., Goles, E., , Pellegrin, D., 1985. Decreasing energy functions as a tool for studying threshold networks. Discrete Applied Mathematics 12, 261-277. OR networks: Goles, E., Noual, M., 2012. Disjunctive networks and update schedules. Advances in Applied Mathematics 48, 646-662.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Non Existence problem

Theorem LCNE is NP-Hard. Proof (idea):

1 2 3 . . . vn

− 1

vn vφ

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Non Existence problem

Theorem LCNE is NP-Hard. Proof (idea):

1 2 3 . . . vn

− 1

vn vφ

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Non Existence problem

Theorem Let F be an OR (AND) function. Then, there exists a sequential update schedule s such that N = (F, s) has only have fixed points as attractors. Proof: Let V ′ be a minimum FVS of the cycles of G F = (V , A) and let consider N = (F, s), with s = sV ′ defined by: sV ′(u, v) = ⊕ if (u, v) ∈ AV ′ ⊖

  • therwise

where AV ′ is a minimal FAS from N+(V ′).

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Limit Cycle Non Existence problem

Remark: The previous Theorem is not valid int the case of AND-OR networks as shown in the following example:

G F f1(x) = x6 ∨ x9 ∨ x11 f2(x) = x6 ∨ x7 ∨ x12 f3(x) = x6 ∨ x8 ∨ x10 f4(x) = x4 f5(x) = x5 f6(x) = x4 ∧ x5 f7(x) = x1 ∧ x4 f8(x) = x2 ∧ x4 f9(x) = x3 ∧ x4 f10(x) = x1 ∧ x5 f11(x) = x2 ∧ x5 f12(x) = x3 ∧ x5

1 2 3 4 5 6 7 8 9 10 11 12

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Summary

1 Definition and Notation 2 Limit Cycle Existence problem 3 Limit Cycle Non Existence problem 4 Feasible Limit Cycle problem

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Feasible Limit Cycle problem

Feasible Limit Cycle problem (FLC) Given a set V of n elements and F = (fv)v∈V : {0, 1}n → {0, 1}n and a sequence C =

  • xkp

k=0 such that xk ∈ {0, 1}n, xk are

pairwise distinct and xp ≡ x0. Does there exist an update schedule s such that C ∈ LC (F, s)?

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Feasible Limit Cycle problem

Theorem OR FLC is NP-Complete. Proof (idea):

φ z0 z1 z2 v1 v2 v3 v4 C 0 C 0

1

C 0

2

C 1 C 2 C 1

1

C 2

1

C 1

2

C 2

2 ⊕ ⊕ ⊕ ⊕ ⊕ ⊕ ⊕ ⊕ ⊕ ⊕ ⊕ ⊖ ⊖ ⊖⊖ ⊖ ⊖ ⊖ ⊖ ⊖ ⊖ ⊖ ⊖ ⊖ ⊕

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Feasible Limit Cycle problem

C0

0 C1 0 C2 0 C0 1 C1 1 C2 1 C0 2 C1 2 C2 2

z0 z1 z2 v1 v2 v3 v4 vφ x0,0 1 1 1 1 1 1 1 x1,0 1 1 1 1 1 1 x2,0 1 1 1 1 x0,1 1 1 1 1 1 1 1 x1,1 1 1 1 1 x2,1 1 1 1 1 1 x0,2 1 1 1 1 1 1 1 x1,2 1 1 1 x2,2 1 1 1 1 1 x0,3 1 1 1 1 1 1 1 φ (w) = (w1 ∨ w2 ∨ ¬w3 ∨ w4) ∧ (¬w2 ∨ w3 ∨ ¬w4) ∧ (¬w1 ∨ ¬w3).

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

Feasible Limit Cycle problem

Theorem FLC is polynomial in the following cases: OR Symmetric OR and cycle of length two. AND-OR and cycle of length two.

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Definition and Notation Limit Cycle Existence problem Limit Cycle Non Existence problem Feasible Limit Cycle problem

The End Merci

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