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Finite-state Gillespie and next-reaction methods have the specified CTMC law
Statement
Assume Countable Choice and Dependent Choice, and let be finite with a reaction system from Finite-channel reaction propensity systems and their generator. Fix an initial state . Supply the independent random streams required by Gillespie direct method with horizon and budget statuses and Next-reaction method by internal Poisson clocks, and use unlimited reaction-event budgets. Define the reference marked process starting at recursively: at state , if , its next reaction time has law and its channel is independent of that time with probabilities ; if , it remains at . Then both algorithms have the law of this reference process on every finite horizon. With a finite event budget, each algorithm instead returns the corresponding reference-process prefix, stopped according to its stated horizon, absorption and budget rules. The process has generator operator absorbing states are handled exactly, and for the expected total reaction count on is at most . A zero-increment channel is still a marked reaction event, but it contributes zero to the state generator.
Facts & Assumptions
Given: Countable Choice, Dependent Choice, a finite state space , an initial state , a finite-channel reaction system, unlimited reaction-event budgets for full-horizon output, and the random input streams with the product laws specified in the algorithm definitions.
A propensity system has total rate and reaction generator operator . (Finite-channel reaction propensity systems and their generator)
Independent unit exponential clocks with rates have first-event time , channel probability , and independent time and channel. (Competing exponential clocks give the reaction event law)
The direct method uses one independent unit exponential and one unit-uniform input per event; the next-reaction method uses independent unit exponential increments in its channel clocks. (Gillespie direct method with horizon and budget statuses, Next-reaction method by internal Poisson clocks)
Independent unit exponential interarrival times give the ordered event-time density on each finite-window ordered simplex, the rate-one case of the homogeneous Poisson event-time law. (Finite-window homogeneous Poisson construction and ordered event-time density)
Under the declared Countable Choice and Dependent Choice assumptions, countable input streams with the required finite-coordinate product laws exist. (Assuming countable and dependent choice, countable products of arbitrary probability spaces)
For a finite state space the rate bound is finite; dominating thinning has accepted event count bounded by a rate- Poisson candidate count with expectation . With the time-constant rates used here, the standard cumulative mark intervals are independent of time and hence have product-measurable time-mark regions, satisfying the exact-thinning theorem's generalized measurability condition. (Dominating thinning has the prescribed reaction law)
Countable Choice is used in the exponential and uniform probability laws. (The Axiom of Countable Choice ())
Dependent Choice is used in the countable product probability-space construction for the input streams. (The axiom of dependent choice: a relation in which every element is related to something admits an -indexed chain)
Proof
For one channel clock sequence with independent unit exponential gaps, the joint density of exactly ordered thresholds and no next threshold by is This agrees with [F4] at unit rate, so each in the next-reaction construction is a unit-rate Poisson process on finite windows. The streams for distinct channels are independent by [F5], and after an event the unused sequence coordinates remain independent: partition on the finite index of the last used coordinate and use the finite-coordinate product law.
At state with , the direct method's waiting time has survival by [F2]. The disjoint cumulative intervals for have lengths , so channel is selected with that probability; because and are independent, the channel is independent of the waiting time. Thus the direct method uses exactly the reference event kernel. If , it returns the absorbing path specified in the Statement.
At a state , the next-reaction clock of channel has residual internal threshold distributed as an independent variable. By [F2] their minimum has the same event-time and channel law as in step 1.2. After a reaction at elapsed time , every nonwinning channel is conditioned only on its threshold exceeding ; memorylessness follows exactly from The residual thresholds remain independent because the conditioning events factor across independent clocks, and the fired channel receives a fresh independent exponential increment. Induction over the reaction count proves that every successive event kernel agrees with step 1.2, hence the full marked path law agrees. The threshold construction also gives by its definition.
Apply the bounded-envelope thinning theorem with the time-constant rates and envelope . It gives finitely many events almost surely and . For bounded and small , the probability of no reaction is ; the probability of exactly one channel- reaction is by its first-event density; and the probability of two or more is by the candidate Poisson bound in [F6]. Therefore which is the operator in [F1]. A zero-increment channel contributes zero to this expression even though its marked event is counted.
Steps 1.2 and 2.1 identify both algorithmic event kernels, starting at the fixed , with the reference kernel; the finite event bound in step 3.1 makes the unlimited-budget comparison a full-horizon path-law equality. A firing at a fixed deterministic horizon has probability zero, since each successive event time has a density conditional on the preceding history; the countable union over event indices is still null. Thus the algorithms' endpoint branches do not alter the path-law conclusion. With a finite budget, the same event-kernel comparison holds up to the algorithm's stopping rule and gives exactly the stated prefix law. Step 3.1 computes the generator and expected event-count bound.
Depends on
- The Axiom of Countable Choice ($\mathrm{AC}_\omega$)
- The axiom of dependent choice: a relation in which every element is related to something admits an $\mathbb{N}$-indexed chain
- Independent random elements
- Law or distribution of a random element
- Lebesgue measurable sets, the family $\mathcal{L}(\mathbb{R}^n)$, and the restricted set function $\lambda_n$
- Random elements and real random variables
- Finite-channel reaction propensity systems and their generator
- Gillespie direct method with horizon and budget statuses
- Next-reaction method by internal Poisson clocks
- Competing exponential clocks give the reaction event law
- Finite-window homogeneous Poisson construction and ordered event-time density
- Assuming countable and dependent choice, countable products of arbitrary probability spaces
- Dominating thinning has the prescribed reaction law
- Exponential and Weibull survival specifications define probability laws
- A box in $\mathbb{R}^n$ with parameters $a_i\le b_i$ is Lebesgue measurable of measure $\prod_{i<n}(b_i-a_i)$, whichever of its faces are included
Used by
- Critical-reaction binomial guarded tau-leaping Algorithm
- Clipping an understated thinning envelope changes the waiting-time law Counterexample
- A zero-total-hazard state is absorbing Example
- Gillespie simulation of a finite birth-death reaction network Example
- Dynkin identity for a bounded-rate finite stopped reaction chain Lemma
- One-step weak defect of finite-state Poisson tau-leaping Lemma
- Compensators, brackets, and jump-integral isometry for reaction counts Theorem
- Weak order one for finite-state Poisson tau-leaping with an exit bound Theorem
Cited to discharge well-definedness by Next-reaction method by internal Poisson clocks.
Dependency tree · two levels
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Sources
- Daniel T. Gillespie, Exact Stochastic Simulation of Coupled Chemical Reactions (standard reference, not scraped)
- David F. Anderson, Introduction to Stochastic Processes with Applications to Biology, Chapters 6–7 (standard reference, not scraped)
- David F. Anderson and Thomas G. Kurtz, Continuous Time Markov Chain Models for Chemical Reaction Networks (standard reference, not scraped)