On Controllability of Delayed Boolean Control Networks: Trajectory Controllability Avoiding Forbidden Trajectories Iff the Reduced Transition-Count Matrix Is IrreducibleResearch Paper
Motivation
Boolean networks model gene regulatory networks by giving each gene an on/off value and updating all values synchronously by logical rules (Kauffman, 1969). Adding external Boolean inputs gives Boolean control networks (BCNs), in which a designer (a drug, an intervention) chooses the inputs over time. The basic control-theoretic question is controllability: can the inputs drive the network from any configuration to any other? Cheng and Qi (Automatica 2009) answered it for BCNs using the semi-tensor product of matrices, which rewrites a BCN as a linear recursion on canonical basis vectors.
Biological regulation is not instantaneous: transcription and translation introduce delays, so the next value of a gene can depend on several past values. Lu, Zhong, Ho, Tang and Cao (SIAM J. Control Optim. 2016) study delayed BCNs, in which the update reads the last states, and give criteria for two kinds of controllability, including the case where some configurations are dangerous and must be avoided (in biology, states corresponding to disease). The mission formalizes their criteria.
Setting
Write . A state is and an input value is . Fix . The delayed BCN (2.2) is
with arbitrary Boolean functions , collected into one map with . A trajectory is the window of the last states; its last entry is the current state. One step maps under the input to . A control sequence of length is , with inputs chosen freely; denotes the trajectory after steps from an initial trajectory .
The transition-count matrix has rows and columns indexed by trajectories: is the number of input values taking trajectory to trajectory in one step. For a set of forbidden trajectories, is with the rows and columns of replaced by zeros, and is with those rows and columns deleted.
The notions of controllability are:
- Trajectory controllable (Definition 3.1): from every initial trajectory, every trajectory equals for some and some control sequence.
- Trajectory controllable under (Definition 3.11): for all trajectories there are and a control sequence steering to with for .
- State controllable (Definition 4.1): from every initial trajectory, every state equals for some and some control sequence.
A real square matrix of size is reducible (Definition 3.7) if a simultaneous permutation of rows and columns brings it to block upper-triangular form with square diagonal blocks; it is irreducible otherwise, so every matrix is irreducible.
counts the control sequences of length steering to while avoiding ; counts those steering the initial trajectory to ; is the set of trajectories with current state .
Formalization targets
Goal: Theorem 3.12
for every , , , every update map and every forbidden set . It is the most general criterion of the paper.
Milestones
- Proposition 3.5: for , .
- Remark 3: .
- Theorem 3.10: trajectory controllable irreducible.
- Theorem 4.3: .
- Theorem 5.1: the same count while avoiding forbidden states , with zeroed on the trajectories containing a state of .
- Corollary 5.3: trajectory controllability implies state controllability.
A supporting item, Lemma 3.9 (corrected form), relates Definition 3.7 to positivity of entries of powers for nonnegative matrices of size at least 2.
Significance
The criteria replace a question about control sequences of unbounded length by a finite test on one nonnegative integer matrix of size . The counting identities give more than a yes/no answer: they enumerate the control sequences achieving a transfer, which is what a designer choosing among interventions needs, and they handle forbidden states by passing to forbidden trajectories.
The results are proved in the paper; none of them has a machine-checked proof. Formalizing them yields a reusable Lean model of delayed (and, for , ordinary) Boolean control networks defined directly through their dynamics, together with a checked bridge from dynamic reachability to the combinatorics of nonnegative matrices. A formal version also pins down points the printed text leaves loose: Lemma 3.9 as printed is false (it characterizes primitive, not irreducible, matrices), and the two different matrices (zeroed) and (deleted) must not be confused.
Difficulty
The central step is the passage between three objects: reachability under the dynamics, positivity of entries of powers of , and the block-triangular definition of irreducibility. The counting identity for powers of is a statement about sequences of inputs, not about paths in a graph, so the bijection between control sequences and weighted walks has to be established with the avoidance constraint carried at every intermediate time, including the endpoints. The equivalence between Definition 3.7 and strong connectivity is the classical graph-theoretic characterization, but it has edge cases the obvious argument misses: a zero matrix is irreducible by Definition 3.7 yet has no positive power, which is exactly why Definition 3.11 allows while Definition 3.1 does not. A proof that routes through "some power of is entrywise positive", following the printed Lemma 3.9, proves a false intermediate statement.
Formalization scope
Conventions committed to in Lean:
- A state is
Fin n → Bool(trueis the paper's 1); a trajectory isFin μ → State nwith index 0 the oldest state and index the current state; is a standing assumption (NeZero μ); are arbitrary and no assumption is placed on the update functions. - Matrices are indexed by trajectories rather than by the paper's index of . The paper's is obtained by the simultaneous relabelling of Lemma 2.6, and every statement (entries of powers, sums over sets of trajectories, Definition 3.7) is invariant under it. is indexed by the subtype of allowed trajectories.
- Irreducibility is Definition 3.7 applied to the matrix with entries cast to ; it is not Mathlib's
Matrix.IsIrreducible, which differs on matrices. - Pinned readings: Definition 3.1 and Definition 4.1 use ; Definition 3.11 uses ; Proposition 3.5, Theorem 4.3 and Theorem 5.1 are stated for (Proposition 3.5 is false at when ); Remark 3 holds for all . "Avoiding " in Theorem 5.1 means that no state , , lies in , which is the theorem's own middle term . is defined semantically by eq. (4.3), since the printed index range in (4.4) is a misprint. Lemma 3.9 is included in corrected form with .
Controllability is defined through the dynamics and control sequences, never as positivity of entries of powers of ; a formalization that defines reachability by would reduce Theorems 3.10 and 3.12 to library facts and is ruled out.
Needed infrastructure: the correspondence between control sequences and products of entries of (the core of Proposition 3.5), and the equivalence of Definition 3.7 with strong connectivity of the support graph for nonnegative matrices (Mathlib's Matrix.IsIrreducible, Matrix.isIrreducible_iff_exists_pow_pos and Matrix.pow_apply_pos_iff_nonempty_path cover much of the second part for sizes at least 2). Both are reusable beyond this mission, for ordinary BCNs, probabilistic BCNs and finite automata. Contributions of either piece, or of the semi-tensor-product bridge identifying with , are welcome.
Selected references
- J. Lu, J. Zhong, D. W. C. Ho, Y. Tang, J. Cao, On Controllability of Delayed Boolean Control Networks, SIAM J. Control Optim. 54(2):475–494, 2016. https://doi.org/10.1137/140991820
- D. Cheng, H. Qi, Controllability and observability of Boolean control networks, Automatica 45(7):1659–1667, 2009. https://doi.org/10.1016/j.automatica.2009.03.006
- S. A. Kauffman, Metabolic stability and epigenesis in randomly constructed genetic nets, J. Theoret. Biol. 22(3):437–467, 1969. https://doi.org/10.1016/0022-5193(69)90015-0
- A. Berman, R. J. Plemmons, Nonnegative Matrices in the Mathematical Sciences, SIAM Classics in Applied Mathematics 9, 1994. https://doi.org/10.1137/1.9781611971262