Entropy and Information in Biological Systems (Part 2)

4 July, 2014

John Harte, Marc Harper and I are running a workshop! Now you can apply here to attend:

Information and entropy in biological systems, National Institute for Mathematical and Biological Synthesis, Knoxville Tennesee, Wednesday-Friday, 8-10 April 2015.

Click the link, read the stuff and scroll down to “CLICK HERE” to apply. The deadline is 12 November 2014.

Financial support for travel, meals, and lodging is available for workshop attendees who need it. We will choose among the applicants and invite 10-15 of them.

The idea

Information theory and entropy methods are becoming powerful tools in biology, from the level of individual cells, to whole ecosystems, to experimental design, model-building, and the measurement of biodiversity. The aim of this investigative workshop is to synthesize different ways of applying these concepts to help systematize and unify work in biological systems. Early attempts at “grand syntheses” often misfired, but applications of information theory and entropy to specific highly focused topics in biology have been increasingly successful. In ecology, entropy maximization methods have proven successful in predicting the distribution and abundance of species. Entropy is also widely used as a measure of biodiversity. Work on the role of information in game theory has shed new light on evolution. As a population evolves, it can be seen as gaining information about its environment. The principle of maximum entropy production has emerged as a fascinating yet controversial approach to predicting the behavior of biological systems, from individual organisms to whole ecosystems. This investigative workshop will bring together top researchers from these diverse fields to share insights and methods and address some long-standing conceptual problems.

So, here are the goals of our workshop:

• To study the validity of the principle of Maximum Entropy Production (MEP), which states that biological systems – and indeed all open, non-equilibrium systems – act to produce entropy at the maximum rate.

• To familiarize all the participants with applications to ecology of the MaxEnt method: choosing the probabilistic hypothesis with the highest entropy subject to the constraints of our data. We will compare MaxEnt with competing approaches and examine whether MaxEnt provides a sufficient justification for the principle of MEP.

• To clarify relations between known characterizations of entropy, the use of entropy as a measure of biodiversity, and the use of MaxEnt methods in ecology.

• To develop the concept of evolutionary games as “learning” processes in which information is gained over time.

• To study the interplay between information theory and the thermodynamics of individual cells and organelles.

For more details, go here.

If you’ve got colleagues who might be interested in this, please let them know. You can download a PDF suitable for printing and putting on a bulletin board by clicking on this:



The Computational Power of Chemical Reaction Networks

10 June, 2014

I’m at this workshop:

Programming with Chemical Reaction Networks: Mathematical Foundations, Banff International Research Station, 8-13 June 2014.

Luca Cardelli wrote about computation with chemical reactions in Part 26 of the network theory series here on this blog. So, it’s nice to meet him and many other researchers, learn more, and try to solve some problems together!

The first tutorial was this:

• David Soloveichik, U.C. San Francisco, The computational power of chemical reaction networks.

David works at the Center for Systems and Synthetic Biology, and their website says:

David did his graduate work with Erik Winfree at Caltech, focusing on algorithmic self-assembly and on synthetic networks of nucleic-acid interactions based on strand displacement cascades. He is interested in “molecular programming”: the systematic design of complex molecular systems based on the principles of computer science and distributed computing. More generally, he is trying to create a theoretical foundation of chemical computation applicable to both synthetic and natural systems.

According to his webpage, Soloveichik’s research interests are:

Wet-lab: the rational design of molecular interactions for synthetic biology, nanotechnology, and bioengineering. The goal is to engineer autonomous molecular systems that can sense, compute, and perform various actions. Using nucleic-acid “strand displacement cascades” as the molecular primitive, we are able to attain freedom of design that hasn’t been previously possible.

Theory: The theoretical foundation of chemical computation. Once we have a way to program molecular interactions, what programming language shall we use? How molecules can process information and carry out computation is still not well-understood; however, a formal connection to models of concurrent computation may allow systematic and scalable design, rigorous analysis and verification. Further, computational principles may elucidate the design of biological regulatory networks.

Here are my notes on his tutorial.

Motivation

We’ve got people here from different backgrounds:

• computational complexity theory
• wetlab / experimental science
• pure and applied mathematics
• software verification

CRNs (chemical reaction networks) show up in:

• chemistry
• population biology
• sensor networks
• math:
    ○ vector addition systems
    ○ Petri nets
    ○ commutative semigroups
    ○ bounded context-free languages
    ○ uniform recurrence equations

Why use them for computation? People want to go beyond the von Neumann architecture for computation. People also want to understand how cells process information. However, with a few exceptions, the computational perspective in this talk has not yet proved relevant in biology. So, there is a lot left to learn.

The model

The model of computation here will be the master equation for a chemical reaction network… since this has been explained starting Part 4 of the network theory series, I won’t review it!

Can all chemical reaction networks, even those without any conservation laws, be realized by actual chemical systems?

Though this is a subtle question, one answer is “yes, using strand displacement cascades”. This is a trick for getting DNA to simulate other chemical reactions. It’s been carried out in the lab! See this paper and many subsequent ones:

• Soloveichik, Seelig and Winfree, DNA as a universal substrate for chemical kinetics.

Abstract: Molecular programming aims to systematically engineer molecular and chemical systems of autonomous function and ever-increasing complexity. A key goal is to develop embedded control circuitry within a chemical system to direct molecular events. Here we show that systems of DNA molecules can be constructed that closely approximate the dynamic behavior of arbitrary systems of coupled chemical reactions. By using strand displacement reactions as a primitive, we construct reaction cascades with effectively unimolecular and bimolecular kinetics. Our construction allows individual reactions to be coupled in arbitrary ways such that reactants can participate in multiple reactions simultaneously, reproducing the desired dynamical properties. Thus arbitrary systems of chemical equations can be compiled into real chemical systems. We illustrate our method on the Lotka–Volterra oscillator, a limit-cycle oscillator, a chaotic system, and systems implementing feedback digital logic and algorithmic behavior.

However, even working with the master equation for a CRN, there are various things we might mean by having it compute something:

• uniform vs non-uniform: is a single CRN supposed to handle all inputs, or do we allow adding extra reactions for larger inputs? It’s a bit like Turing machines vs Boolean circuits.

• deterministic vs probabilistic: is the correct output guaranteed or merely likely?

• halting vs stabilizing: does the CRN ‘know’ when it has finished, or not? In the ‘halting’ case the CRN irreversibly produces some molecules that signal that the computation is done. In the ‘stabilizing’ case, it eventually stabilizes to the right answer, but we may not know how long to wait.

These distinctions dramatically affect the computational power. In the case of uniform computation:

• deterministic and halting: this has finite computational power.

• deterministic and stabilizing: this can decide semilinear predicates.

• probabilistic and halting: this is Turing-universal.

• probabilistic and stabilizing: this can decide \Delta_2^0 predicates, which are more general than computable ones. (Indeed, if we use Turing machines but don’t require them to signal when they’ve halted, the resulting infinitely long computations can ‘compute’ stuff that’s not computable in the usual sense.)

Deterministic stabilizing computations

Let’s look at the deterministic stabilizing computations in a bit more detail. We’ll look at decision problems. We have a subset S \subseteq \mathbb{N}^d, and we want to answer this question: is the vector X \in \mathbb{N}^d in the set S?

To do this, we represent the vector as a bunch of molecules: X_1 of the first kind, X_2 of the second kind, and so on. We call this an input. We may also include a fixed collection of additional molecules in our input, to help the reactions run.

Then we choose a chemical reaction network, and we let it run on our input. The answer to our question will be encoded in some molecules called Y and N. If X is in S, we want our chemical reaction to produce Y molecules. If it’s not, we want our reaction to produce N’s.

To make this more precise, we need to define what counts as an output. If we’ve got a bunch of molecules that

• contains Y but not N: then the output is YES.

• contains N but not Y: then the output is NO.

Otherwise the output is undefined.

Output-stable states are states with YES or NO output such that all states reachable from them via our chemical reactions give the same output. We say an output-stable-state is correct if this output is the correct answer to the question: is X in S.

Our chemical reaction network gives a deterministic stabilizing computation if for any input, and choosing any state reachable from that input, we can do further chemical reactions to reach a correct output-stable state.

In other words: starting from our input, and letting the chemical reactions <run any way they want, we will eventually stabilize at an output that gives the right answer to the question “is X in S?”

Examples

This sounds a bit complicated, but it’s really not. Let’s look at some examples!

Example 1. Suppose you want to check two numbers and see if one is greater than or equal to another. Here

S = \{(X_1,X_2) : X_2 \ge X_1 \}

How can you decide if a pair of numbers (X_1,X_2) is in this set?

You start with X_1 molecules of type A, X_2 molecules of type B, and one molecule of type Y. Then you use a chemical reaction network with these reactions:

A + N \to Y
B + Y \to N

If you let these reactions run, the Y switches to a N each time the reactions destroy an A. But the N switches back to a Y each time the reactions destroy a B.

When no more reactions are possible, we are left with either one Y or one N, which is the correct answer to your question!

Example 2. Suppose you want to check two numbers and see if one is equal to another. Here

S = \{(X_1,X_2) : X_2 = X_1 \}

How can you decide if a pair of numbers (X_1,X_2) is in here?

This is a bit harder! As before, you start with X_1 molecules of type A, X_2 molecules of type B, and one molecule of type Y. Then you use a chemical reaction network with these reactions:

A + B \to Y
Y + N \to Y
A + Y \to A + N
B + Y \to B + N

The first reaction lets an A and a B cancel out, producing a Y. If you only run this reaction, you’ll eventually be left with either a bunch of A\mathrm{s} or a bunch of B\mathrm{s} or nothing but Y\mathrm{s}.

If you have Y\mathrm{s}, your numbers were equal. The other reactions deal with the cases where you have A\mathrm{s} or B\mathrm{s} left over. But the key thing to check is that no matter what order we run the reactions, we’ll eventually get the right answer! In the end, you’ll have either Y\mathrm{s} or N\mathrm{s}, not both, and this will provide the yes-or-no answer to the question of whether X_1 = X_2.

What deterministic stabilizing computations can do

We’ve looked at some examples of deterministic stabilizing computations. The big question is: what kind of questions can they answer?

More precisely, for what subsets A \subseteq \mathbb{N}^d can we build a deterministic stabilizing computation that ends with output YES if the input X lies in A and with output NO otherwise?

The answer is: the ‘semilinear’ subsets!

• Dana Angluin, James Aspnes and David Eistenstat, Stably computable predicates are semilinear.

A set S \subseteq \mathbb{N}^d is linear if it’s of the form

\{u_0 + n_1 u_1 + \cdots + n_p u_p : n_i \in \mathbb{N}  \}

for some fixed vectors of natural numbers u_i \in \mathbb{N}^d.

A set S \subseteq \mathbb{N}^d semilinear if it’s a finite union of linear sets.

How did Angluin, Aspnes and Eisenstat prove their theorem? Apparently the easy part is showing that membership in any semilinear set can be decided by a chemical reaction network. David sketched the proof of the converse. I won’t go into it, but it used a very nice fact:

Dickson’s Lemma. Any subset of \mathbb{N}^d has a finite set of minimal elements, where we define x \le y if x_i \le y_i for all i.

For example, the region above and to the right of the hyperbola here has five minimal elements:

If you know some algebra, Dickson’s lemma should remind you of the Hilbert basis theorem, saying (for example) that every ideal in a ring of multivariable polynomials over a field is finitely generated. And in fact, Paul Gordan used Dickson’s Lemma in 1899 to help give a proof of Hilbert’s basis theorem.

It’s very neat to see how this lemma applies to chemical reaction networks! You can see how it works in Angluin, Aspnes and Eistenstat’s paper. But they call it “Higman’s lemma” for some reason.

References

Here are some of David Soloveichik’s recent talks:

• An introduction to strand displacement cascades for the Foresight Institute Conference (Palo Alto, Jan 2013): An artificial “biochemistry” with DNA.

• Paper presented at DNA Computing and Molecular Programming 18 (Aarhus, Denmark, Aug 2012): Deterministic function computation with chemical reaction networks.

• Tutorial talk for DNA Computing and Molecular Programming 17 (Pasadena, Aug 2011): The programming language of chemical kinetics, and how to discipline your DNA molecules using strand displacement cascades.

• High-level introduction to algorithmic self-assembly and stochastic chemical reaction networks as computer-theoretic models: Computer-theoretic abstractions for molecular programming.

• On algorithmic behavior in chemical reaction networks and implementing arbitrary chemical reaction networks with DNA: programming well-mixed chemical kinetics.


Relative Entropy in Evolutionary Dynamics

22 January, 2014

guest post by Marc Harper

In John’s information geometry series, he mentioned some of my work in evolutionary dynamics. Today I’m going to tell you about some exciting extensions!

The replicator equation

First a little refresher. For a population of n replicating types, such as individuals with different eye colors or a gene with n distinct alleles, the ‘replicator equation’ expresses the main idea of natural selection: the relative rate of growth of each type should be proportional to the difference between the fitness of the type and the mean fitness in the population.

To see why this equation should be true, let P_i be the population of individuals of the ith type, which we allow to be any nonnegative real number. We can list all these numbers and get a vector:

P = (P_1, \dots, P_n)

The Lotka–Volterra equation is a very general rule for how these numbers can change with time:

\displaystyle{ \frac{d P_i}{d t} = f_i(P) P_i }

Each population grows at a rate proportional to itself, where the ‘constant of proportionality’, f_i(P), is not necessarily constant: it can be any real-valued function of P. This function is called the fitness of the ith type. Taken all together, these functions f_i are called the fitness landscape.

Let p_i be the fraction of individuals who are of the ith type:

\displaystyle{ p_i = \frac{P_i}{\sum_{i =1}^n P_i } }

These numbers p_i are between 0 and 1, and they add up to 1. So, we can also think of them as probabilities: p_i is the probability that a randomly chosen individual is of the ith type. This is how probability theory, and eventually entropy, gets into the game.

Again, we can bundle these numbers into a vector:

p = (p_1, \dots, p_n)

which we call the population distribution. It turns out that the Lotka–Volterra equation implies the replicator equation:

\displaystyle{ \frac{d p_i}{d t} = \left( f_i(P) - \langle f(P) \rangle \right) \, p_i }

where

\displaystyle{ \langle f(P) \rangle = \sum_{i =1}^n  f_i(P)  p_i  }

is the mean fitness of all the individuals. You can see the proof in Part 9 of the information geometry series.

By the way: if each fitness f_i(P) only depends on the fraction of individuals of each type, not the total numbers, we can write the replicator equation in a simpler way:

\displaystyle{ \frac{d p_i}{d t} = \left( f_i(p) - \langle f(p) \rangle \right) \, p_i }

From now on, when talking about this equation, that’s what I’ll do.

Anyway, the take-home message is this: the replicator equation says the fraction of individuals of any type changes at a rate proportional to fitness of that type minus the mean fitness.

Now, it has been known since the late 1970s or early 1980s, thanks to the work of Akin, Bomze, Hofbauer, Shahshahani, and others, that the replicator equation has some very interesting properties. For one thing, it often makes ‘relative entropy’ decrease. For another, it’s often an example of ‘gradient flow’. Let’s look at both of these in turn, and then talk about some new generalizations of these facts.

Relative entropy as a Lyapunov function

I mentioned that we can think of a population distribution as a probability distribution. This lets us take ideas from probability theory and even information theory and apply them to evolutionary dynamics! For example, given two population distributions p and q, the information of q relative to p is

I(q,p) = \displaystyle{ \sum_i q_i \ln \left(\frac{q_i}{p_i }\right)}

This measures how much information you gain if you have a hypothesis about some state of affairs given by the probability distribution p, and then someone tells you “no, the best hypothesis is q!”

It may seem weird to treat a population distribution as a hypothesis, but this turns out to be a good idea. Evolution can then be seen as a learning process: a process of improving the hypothesis.

We can make this precise by seeing how the relative information changes with the passage of time. Suppose we have two population distributions q and p. Suppose q is fixed, while p evolves in time according to the replicator equation. Then

\displaystyle{  \frac{d}{d t} I(q,p)  =  \sum_i f_i(P) (p_i - q_i) }

For the proof, see Part 11 of the information geometry series.

So, the information of q relative to p will decrease as p evolves according to the replicator equation if

\displaystyle{  \sum_i f_i(P) (p_i - q_i) } \le 0

If q makes this true for all p, we say q is an evolutionarily stable state. For some reasons why, see Part 13.

What matters now is that when q is an evolutionarily stable state, I(q,p) says how much information the population has ‘left to learn’—and we’re seeing that this always decreases. Moreover, it turns out that we always have

I(q,p) \ge 0

and I(q,p) = 0 precisely when p = q.

People summarize all this by saying that relative information is a ‘Lyapunov function’. Very roughly, a Lyapunov function is something that decreases with the passage of time, and is zero only at the unique stable state. To be a bit more precise, suppose we have a differential equation like

\displaystyle{  \frac{d}{d t} x(t) = v(x(t)) }

where x(t) \in \mathbb{R}^n and v is some smooth vector field on \mathbb{R}^n. Then a smooth function

V : \mathbb{R}^n \to \mathbb{R}

is a Lyapunov function if

V(x) \ge 0 for all x

V(x) = 0 iff x is some particular point x_0

and

\displaystyle{ \frac{d}{d t} V(x(t)) \le 0 } for every solution of our differential equation.

In this situation, the point x_0 is a stable equilibrium for our differential equation: this is Lyapunov’s theorem.

The replicator equation as a gradient flow equation

The basic idea of Lyapunov’s theorem is that when a ball likes to roll downhill and the landscape has just one bottom point, that point will be the unique stable equilibrium for the ball.

The idea of gradient flow is similar, but different: sometimes things like to roll downhill as efficiently as possible: they move in the exactly the best direction to make some quantity smaller! Under certain conditions, the replicator equation is an example of this phenomenon.

Let’s fill in some details. For starters, suppose we have some function

F : \mathbb{R}^n \to \mathbb{R}

Think of V as ‘height’. Then the gradient flow equation says how a point x(t) \in \mathbb{R}^n will move if it’s always trying its very best to go downhill:

\displaystyle{ \frac{d}{d t} x(t) = - \nabla V(x(t)) }

Here \nabla is the usual gradient in Euclidean space:

\displaystyle{ \nabla V = \left(\partial_1 V, \dots, \partial_n V \right)  }

where \partial_i is short for the partial derivative with respect to the ith coordinate.

The interesting thing is that under certain conditions, the replicator equation is an example of a gradient flow equation… but typically not one where \nabla is the usual gradient in Euclidean space. Instead, it’s the gradient on some other space, the space of all population distributions, which has a non-Euclidean geometry!

The space of all population distributions is a simplex:

\{ p \in \mathbb{R}^n : \; p_i \ge 0, \; \sum_{i = 1}^n p_i = 1 \} .

For example, it’s an equilateral triangle when n = 3. The equilateral triangle looks flat, but if we measure distances another way it becomes round, exactly like a portion of a sphere, and that’s the non-Euclidean geometry we need!

In fact this trick works in any dimension. The idea is to give the simplex a special Riemannian metric, the ‘Fisher information metric’. The usual metric on Euclidean space is

\delta_{i j} = \left\{\begin{array}{ccl} 1 & \mathrm{ if } & i = j \\                                       0 &\mathrm{ if } & i \ne j \end{array} \right.

This simply says that two standard basis vectors like (0,1,0,0) and (0,0,1,0) have dot product zero if the 1’s are in different places, and one if they’re in the same place. The Fisher information metric is a bit more complicated:

\displaystyle{ g_{i j} = \frac{\delta_{i j}}{p_i} }

As before, g_{i j} is a formula for the dot product of the ith and jth standard basis vectors, but now it depends on where you are in the simplex of population distributions.

We saw how this formula arises from information theory back in Part 7. I won’t repeat the calculation, but the idea is this. Fix a population distribution p and consider the information of another one, say q, relative to this. We get I(q,p). If q = p this is zero:

\displaystyle{ \left. I(q,p)\right|_{q = p} = 0 }

and this point is a local minimum for the relative information. So, the first derivative of I(q,p) as we change q must be zero:

\displaystyle{ \left. \frac{\partial}{\partial q_i} I(q,p) \right|_{q = p} = 0 }

But the second derivatives are not zero. In fact, since we’re at a local minimum, it should not be surprising that we get a positive definite matrix of second derivatives:

\displaystyle{  g_{i j} = \left. \frac{\partial^2}{\partial q_i \partial q_j} I(q,p) \right|_{q = p} = 0 }

And, this is the Fisher information metric! So, the Fisher information metric is a way of taking dot products between vectors in the simplex of population distribution that’s based on the concept of relative information.

This is not the place to explain Riemannian geometry, but any metric gives a way to measure angles and distances, and thus a way to define the gradient of a function. After all, the gradient of a function should point at right angles to the level sets of that function, and its length should equal the slope of that function:

So, if we change our way of measuring angles and distances, we get a new concept of gradient! The ith component of this new gradient vector field turns out to b

(\nabla_g V)^i = g^{i j} \partial_j V

where g^{i j} is the inverse of the matrix g_{i j}, and we sum over the repeated index j. As a sanity check, make sure you see why this is the usual Euclidean gradient when g_{i j} = \delta_{i j}.

Now suppose the fitness landscape is the good old Euclidean gradient of some function. Then it turns out that the replicator equation is a special case of gradient flow on the space of population distributions… but where we use the Fisher information metric to define our concept of gradient!

To get a feel for this, it’s good to start with the Lotka–Volterra equation, which describes how the total number of individuals of each type changes. Suppose the fitness landscape is the Euclidean gradient of some function V:

\displaystyle{ f_i(P) = \frac{\partial V}{\partial P_i} }

Then the Lotka–Volterra equation becomes this:

\displaystyle{ \frac{d P_i}{d t} = \frac{\partial V}{\partial P_i} \, P_i }

This doesn’t look like the gradient flow equation, thanks to that annoying P_i on the right-hand side! It certainly ain’t the gradient flow coming from the function V and the usual Euclidean gradient. However, it is gradient flow coming from V and some other metric on the space

\{ P \in \mathbb{R}^n : \; P_i \ge 0 \}

For a proof, and the formula for this other metric, see Section 3.7 in this survey:

• Marc Harper, Information geometry and evolutionary game theory.

Now let’s turn to the replicator equation:

\displaystyle{ \frac{d p_i}{d t} = \left( f_i(p)  - \langle f(p) \rangle \right) \, p_i }

Again, if the fitness landscape is a Euclidean gradient, we can rewrite the replicator equation as a gradient flow equation… but again, not with respect to the Euclidean metric. This time we need to use the Fisher information metric! I sketch a proof in my paper above.

In fact, both these results were first worked out by Shahshahani:

• Siavash Shahshahani, A New Mathematical Framework for the Study of Linkage and Selection, Memoirs of the AMS 17, 1979.

New directions

All this is just the beginning! The ideas I just explained are unified in information geometry, where distance-like quantities such as the relative entropy and the Fisher information metric are studied. From here it’s a short walk to a very nice version of Fisher’s fundamental theorem of natural selection, which is familiar to researchers both in evolutionary dynamics and in information geometry.

You can see some very nice versions of this story for maximum likelihood estimators and linear programming here:

• Akio Fujiwara and Shun-ichi Amari, Gradient systems in view of information geometry, Physica D: Nonlinear Phenomena 80 (1995), 317–327.

Indeed, this seems to be the first paper discussing the similarities between evolutionary game theory and information geometry.

Dash Fryer (at Pomona College) and I have generalized this story in several interesting ways.

First, there are two famous ways to generalize the usual formula for entropy: Tsallis entropy and Rényi entropy, both of which involve a parameter q. There are Tsallis and Rényi versions of relative entropy and the Fisher information metric as well. Everything I just explained about:

• conditions under which relative entropy is a Lyapunov function for the replicator equation, and

• conditions under which the replicator equation is a special case of gradient flow

generalize to these cases! However, these generalized entropies give modified versions of the replicator equation. When we set q=1 we get back the usual story. See

• Marc Harper, Escort evolutionary game theory.

My initial interest in these alternate entropies was mostly mathematical—what is so special about the corresponding geometries?—but now researchers are starting to find populations that evolve according to these kinds of modified population dynamics! For example:

• A. Hernando et al, The workings of the Maximum Entropy Principle in collective human behavior.

There’s an interesting special case worth some attention. Lots of people fret about the relative entropy not being a distance function obeying the axioms that mathematicians like: for example, it doesn’t obey the triangle inequality. Many describe the relative entropy as a distance-like function, and this is often a valid interpretation contextually. On the other hand, the q=0 relative entropy is one-half the Euclidean distance squared! In this case the modified version of the replicator equation looks like this:

\displaystyle{ \frac{d p_i}{d t} = f_i(p) - \frac{1}{n} \sum_{j = 1}^n f_j(p) }

This equation is called the projection dynamic.

Later, I showed that there is a reasonable definition of relative entropy for a much larger family of geometries that satisfies a similar distance minimization property.

In a different direction, Dash showed that you can change the way that selection acts by using a variety of alternative ‘incentives’, extending the story to some other well-known equations describing evolutionary dynamics. By replacing the terms x_i f_i(x) in the replicator equation with a variety of other functions, called incentives, we can generate many commonly studied models of evolutionary dynamics. For instance if we exponentiate the fitness landscape (to make it always positive), we get what is commonly known as the logit dynamic. This amounts to changing the fitness landscape as follows:

\displaystyle{ f_i \mapsto \frac{x_i e^{\beta f_i}}{\sum_j{x_j e^{\beta f_j}}} }

where \beta is known as an inverse temperature in statistical thermodynamics and as an intensity of selection in evolutionary dynamics. There are lots of modified versions of the replicator equation, like the best-reply and projection dynamics, more common in economic applications of evolutionary game theory, and they can all be captured in this family. (There are also other ways to simultaneously capture such families, such as Bill Sandholm’s revision protocols, which were introduced earlier in his exploration of the foundations of game dynamics.)

Dash showed that there is a natural generalization of evolutionarily stable states to ‘incentive stable states’, and that for incentive stable states, the relative entropy is decreasing to zero when the trajectories get near the equilibrium. For the logit and projection dynamics, incentive stable states are simply evolutionarily stable states, and this happens frequently, but not always.

The third generalization is to look at different ‘time-scales’—that is, different ways of describing time! We can make up the symbol \mathbb{T} for a general choice of ‘time-scale’. So far I’ve been treating time as a real number, so

\mathbb{T} = \mathbb{R}

But we can also treat time as coming in discrete evenly spaced steps, which amounts to treating time as an integer:

\mathbb{T} = \mathbb{Z}

More generally, we can make the steps have duration h, where h is any positive real number:

\mathbb{T} = h\mathbb{Z}

There is a nice way to simultaneously describe the cases \mathbb{T} = \mathbb{R} and \mathbb{T} = h\mathbb{Z} using the time-scale calculus and time-scale derivatives. For the time-scale \mathbb{T} = \mathbb{R} the time-scale derivative is just the ordinary derivative. For the time-scale \mathbb{T} = h\mathbb{Z}, the time-scale derivative is given by the difference quotient from first year calculus:

\displaystyle{ f^{\Delta}(z) = \frac{f(z+h) - f(z)}{h} }

and using this as a substitute for the derivative gives difference equations like a discrete-time version of the replicator equation. There are many other choices of time-scale, such as the quantum time-scale given by \mathbb{T} = q^{\mathbb{Z}}, in which case the time-scale derivative is called the q-derivative, but that’s a tale for another time. In any case, the fact that the successive relative entropies are decreasing can be simply state by saying they have negative \mathbb{T} = h\mathbb{Z} time-scale derivative. The continuous case we started with corresponds to \mathbb{T} = \mathbb{R}.

Remarkably, Dash and I were able to show that you can combine all three of these generalizations into one theorem, and even allow for multiple interacting populations! This produces some really neat population trajectories, such as the following two populations with three types, with fitness functions corresponding to the rock-paper-scissors game. On top we have the replicator equation, which goes along with the Fisher information metric; on the bottom we have the logit dynamic, which goes along with the Euclidean metric on the simplex:

From our theorem, it follows that the relative entropy (ordinary relative entropy on top, the q = 0 entropy on bottom) converges to zero along the population trajectories.

The final form of the theorem is loosely as follows. Pick a Riemannian geometry given by a metric g (obeying some mild conditions) and an incentive for each population, as well as a time scale (\mathbb{R} or h \mathbb{Z}) for every population. This gives an evolutionary dynamic with a natural generalization of evolutionarily stable states, and a suitable version of the relative entropy. Then, if there is an evolutionarily stable state in the interior of the simplex, the time-scale derivative of sum of the relative entropies for each population will decrease as the trajectories converge to the stable state!

When there isn’t such a stable state, we still get some interesting population dynamics, like the following:


See this paper for details:

• Marc Harper and Dashiell E. A. Fryer, Stability of evolutionary dynamics on time scales.

Next time we’ll see how to make the main idea work in finite populations, without derivatives or deterministic trajectories!


Life’s Struggle to Survive

19 December, 2013

Here’s the talk I gave at the SETI Institute:

When pondering the number of extraterrestrial civilizations, it is worth noting that even after it got started, the success of life on Earth was not a foregone conclusion. In this talk, I recount some thrilling episodes from the history of our planet, some well-documented but others merely theorized: our collision with the planet Theia, the oxygen catastrophe, the snowball Earth events, the Permian-Triassic mass extinction event, the asteroid that hit Chicxulub, and more, including the massive environmental changes we are causing now. All of these hold lessons for what may happen on other planets!

To watch the talk, click on the video above. To see
slides of the talk, click here!

Here’s a mistake in my talk that doesn’t appear in the slides: I suggested that Theia started at the Lagrange point in Earth’s orbit. After my talk, an expert said that at that time, the Solar System had lots of objects with orbits of high eccentricity, and Theia was probably one of these. He said the Lagrange point theory is an idiosyncratic theory, not widely accepted, that somehow found its way onto Wikipedia.

Another issue was brought up in the questions. In a paper in Science, Sherwood and Huber argued that:

Any exceedence of 35 °C for extended periods should
induce hyperthermia in humans and other mammals, as dissipation of metabolic heat becomes impossible. While this never happens now, it would begin to occur with global-mean warming of about 7 °C, calling the habitability of some regions into question. With 11-12 °C warming, such regions would spread to encompass the majority of the human population as currently distributed. Eventual warmings of 12 °C are
possible from fossil fuel burning.

However, the Paleocene-Eocene Thermal Maximum seems to have been even hotter:

So, the question is: where did mammals live during this period, which mammals went extinct, if any, and does the survival of other mammals call into question Sherwood and Huber’s conclusion?


Entropy and Information in Biological Systems (Part 1)

2 November, 2013

John Harte is an ecologist who uses maximum entropy methods to predict the distribution, abundance and energy usage of species. Marc Harper uses information theory in bioinformatics and evolutionary game theory. Harper, Harte and I are organizing a workshop on entropy and information in biological systems, and I’m really excited about it!

It’ll take place at the National Institute for Mathematical and Biological Synthesis in Knoxville Tennesee. We are scheduling it for Wednesday-Friday, April 8-10, 2015. When the date gets confirmed, I’ll post an advertisement so you can apply to attend.

Writing the proposal was fun, because we got to pull together lots of interesting people who are applying information theory and entropy to biology in quite different ways. So, here it is!

Proposal

Ever since Shannon initiated research on information theory in 1948, there have been hopes that the concept of information could serve as a tool to help systematize and unify work in biology. The link between information and entropy was noted very early on, and it suggested that a full thermodynamic understanding of biology would naturally involve the information processing and storage that are characteristic of living organisms. However, the subject is full of conceptual pitfalls for the unwary, and progress has been slower than initially expected. Premature attempts at ‘grand syntheses’ have often misfired. But applications of information theory and entropy to specific highly focused topics in biology have been increasingly successful, such as:

• the maximum entropy principle in ecology,
• Shannon and Rényi entropies as measures of biodiversity,
• information theory in evolutionary game theory,
• information and the thermodynamics of individual cells.

Because they work in diverse fields, researchers in these specific topics have had little opportunity to trade insights and take stock of the progress so far. The aim of the workshop is to do just this.

In what follows, participants’ names are in boldface, while the main goals of the workshop are in italics.

Roderick Dewar is a key advocate of the principle of Maximum Entropy Production, which says that biological systems—and indeed all open, non-equilibrium systems—act to produce entropy at the maximum rate. Along with others, he has applied this principle to make testable predictions in a wide range of biological systems, from ATP synthesis [DJZ2006] to respiration and photosynthesis of individual plants [D2010] and plant communities. He has also sought to derive this principle from ideas in statistical mechanics [D2004, D2009], but it remains controversial.

The first goal of this workshop is to study the validity of this principle.

While they may be related, the principle of Maximum Entropy Production should not be confused with the MaxEnt inference procedure, which says that we should choose the probabilistic hypothesis with the highest entropy subject to the constraints provided by our data. MaxEnt was first explicitly advocated by Jaynes. He noted that it is already implicit in the procedures of statistical mechanics, but convincingly argued that it can also be applied to situations where entropy is more ‘informational’ than ‘thermodynamic’ in character.

Recently John Harte has applied MaxEnt in this way to ecology, using it to make specific testable predictions for the distribution, abundance and energy usage of species across spatial scales and across habitats and taxonomic groups [Harte2008, Harte2009, Harte2011]. Annette Ostling is an expert on other theories that attempt to explain the same data, such as the ‘neutral model’ [AOE2008, ODLSG2009, O2005, O2012]. Dewar has also used MaxEnt in ecology [D2008], and he has argued that it underlies the principle of Maximum Entropy Production.

Thus, a second goal of this workshop is to familiarize all the participants with applications of the MaxEnt method to ecology, compare it with competing approaches, and study whether MaxEnt provides a sufficient justification for the principle of Maximum Entropy Production.

Entropy is not merely a predictive tool in ecology: it is also widely used as a measure of biodiversity. Here Shannon’s original concept of entropy naturally generalizes to ‘Rényi entropy’, which depends on a parameter \alpha \ge 0. This equals

\displaystyle{ H_\alpha(p) = \frac{1}{1-\alpha} \log \sum_i p_i^\alpha  }

where p_i is the fraction of organisms of the ith type (which could mean species, some other taxon, etc.). In the limit \alpha \to 1 this reduces to the Shannon entropy:

\displaystyle{  H(p) = - \sum_i p_i \log p_i }

As \alpha increases, we give less weight to rare types of organisms. Christina Cobbold and Tom Leinster have described a systematic and highly flexible system of biodiversity measurement, with Rényi entropy at its heart [CL2012]. They consider both the case where all we have are the numbers p_i, and the more subtle case where we take the distance between different types of organisms into account.

John Baez has explained the role of Rényi entropy in thermodynamics [B2011], and together with Tom Leinster and Tobias Fritz he has proved other theorems characterizing entropy which explain its importance for information processing [BFL2011]. However, these ideas have not yet been connected to the widespread use of entropy in biodiversity studies. More importantly, the use of entropy as a measure of biodiversity has not been clearly connected to MaxEnt methods in ecology. Does the success of MaxEnt methods imply a tendency for ecosystems to maximize biodiversity subject to the constraints of resource availability? This seems surprising, but a more nuanced statement along these general lines might be correct.

So, a third goal of this workshop is to clarify relations between known characterizations of entropy, the use of entropy as a measure of biodiversity, and the use of MaxEnt methods in ecology.

As the amount of data to analyze in genomics continues to surpass the ability of humans to analyze it, we can expect automated experiment design to become ever more important. In Chris Lee and Marc Harper’s RoboMendel program [LH2013], a mathematically precise concept of ‘potential information’—how much information is left to learn—plays a crucial role in deciding what experiment to do next, given the data obtained so far. It will be useful for them to interact with William Bialek, who has expertise in estimating entropy from empirical data and using it to constrain properties of models [BBS, BNS2001, BNS2002], and Susanne Still, who applies information theory to automated theory building and biology [CES2010, PS2012].

However, there is another link between biology and potential information. Harper has noted that in an ecosystem where the population of each type of organism grows at a rate proportional to its fitness (which may depend on the fraction of organisms of each type), the quantity

\displaystyle{ I(q||p) = \sum_i q_i \ln(q_i/p_i) }

always decreases if there is an evolutionarily stable state [Harper2009]. Here p_i is the fraction of organisms of the ith genotype at a given time, while q_i is this fraction in the evolutionarily stable state. This quantity is often called the Shannon information of q ‘relative to’ p. But in fact, it is precisely the same as Lee and Harper’s potential information! Indeed, there is a precise mathematical analogy between evolutionary games and processes where a probabilistic hypothesis is refined by repeated experiments.

Thus, a fourth goal of this workshop is to develop the concept of evolutionary games as ‘learning’ processes in which information is gained over time.

We shall try to synthesize this with Carl Bergstrom and Matina Donaldson-Matasci’s work on the ‘fitness value of information': a measure of how much increase in fitness a population can obtain per bit of extra information [BL2004, DBL2010, DM2013]. Following Harper, we shall consider not only relative Shannon entropy, but also relative Rényi entropy, as a measure of information gain [Harper2011].

A fifth and final goal of this workshop is to study the interplay between information theory and the thermodynamics of individual cells and organelles.

Susanne Still has studied the thermodynamics of prediction in biological systems [BCSS2012]. And in a celebrated related piece of work, Jeremy England used thermodynamic arguments to a derive a lower bound for the amount of entropy generated during a process of self-replication of a bacterial cell [England2013]. Interestingly, he showed that E. coli comes within a factor of 3 of this lower bound.

In short, information theory and entropy methods are becoming powerful tools in biology, from the level of individual cells, to whole ecosystems, to experimental design, model-building, and the measurement of biodiversity. The time is ripe for an investigative workshop that brings together experts from different fields and lets them share insights and methods and begin to tackle some of the big remaining questions.

Bibliography

[AOE2008] D. Alonso, A. Ostling and R. Etienne, The assumption of symmetry and species abundance distributions, Ecology Letters 11 (2008), 93–105.

[TMMABB2012} D. Amodei, W. Bialek, M. J. Berry II, O. Marre, T. Mora, and G. Tkacik, The simplest maximum entropy model for collective behavior in a neural network, arXiv:1207.6319 (2012).

[B2011] J. Baez, Rényi entropy and free energy, arXiv:1102.2098 (2011).

[BFL2011] J. Baez, T. Fritz and T. Leinster, A characterization of entropy in terms of information loss, Entropy 13 (2011), 1945–1957.

[B2011] J. Baez and M. Stay, Algorithmic thermodynamics, Math. Struct. Comp. Sci. 22 (2012), 771–787.

[BCSS2012] A. J. Bell, G. E. Crooks, S. Still and D. A Sivak, The thermodynamics of prediction, Phys. Rev. Lett. 109 (2012), 120604.

[BL2004] C. T. Bergstrom and M. Lachmann, Shannon information and biological fitness, in IEEE Information Theory Workshop 2004, IEEE, 2004, pp. 50-54.

[BBS] M. J. Berry II, W. Bialek and E. Schneidman, An information theoretic approach to the functional classification of neurons, in Advances in Neural Information Processing Systems 15, MIT Press, 2005.

[BNS2001] W. Bialek, I. Nemenman and N. Tishby, Predictability, complexity and learning, Neural Computation 13 (2001), 2409–2463.

[BNS2002] W. Bialek, I. Nemenman and F. Shafee, Entropy and inference, revisited, in Advances in Neural Information Processing Systems 14, MIT Press, 2002.

[CL2012] C. Cobbold and T. Leinster, Measuring diversity: the importance of species similarity, Ecology 93 (2012), 477–489.

[CES2010] J. P. Crutchfield, S. Still and C. Ellison, Optimal causal inference: estimating stored information and approximating causal architecture, Chaos 20 (2010), 037111.

[D2004] R. C. Dewar, Maximum entropy production and non-equilibrium statistical mechanics, in Non-Equilibrium Thermodynamics and Entropy Production: Life, Earth and Beyond, eds. A. Kleidon and R. Lorenz, Springer, New York, 2004, 41–55.

[DJZ2006] R. C. Dewar, D. Juretíc, P. Zupanovíc, The functional design of the rotary enzyme ATP synthase is consistent with maximum entropy production, Chem. Phys. Lett. 430 (2006), 177–182.

[D2008] R. C. Dewar, A. Porté, Statistical mechanics unifies different ecological patterns, J. Theor. Bio. 251 (2008), 389–403.

[D2009] R. C. Dewar, Maximum entropy production as an inference algorithm that translates physical assumptions into macroscopic predictions: don’t shoot the messenger, Entropy 11 (2009), 931–944.

[D2010] R. C. Dewar, Maximum entropy production and plant optimization theories, Phil. Trans. Roy. Soc. B 365 (2010) 1429–1435.

[DBL2010} M. C. Donaldson-Matasci, C. T. Bergstrom, and
M. Lachmann, The fitness value of information, Oikos 119 (2010), 219-230.

[DM2013] M. C. Donaldson-Matasci, G. DeGrandi-Hoffman, and A. Dornhaus, Bigger is better: honey bee colonies as distributed information-gathering systems, Animal Behaviour 85 (2013), 585–592.

[England2013] J. L. England, Statistical physics of self-replication, J. Chem. Phys. 139 (2013), 121923.

[ODLSG2009} J. L. Green, J. K. Lake, J. P. O’Dwyer, A. Ostling and V. M. Savage, An integrative framework for stochastic, size-structured community assembly, PNAS 106 (2009), 6170–6175.

[Harper2009] M. Harper, Information geometry and evolutionary game theory, arXiv:0911.1383 (2009).

[Harper2011] M. Harper, Escort evolutionary game theory, Physica D 240 (2011), 1411–1415.

[Harte2008] J. Harte, T. Zillio, E. Conlisk and A. Smith, Maximum entropy and the state-variable approach to macroecology, Ecology 89 (2008), 2700–2711.

[Harte2009] J. Harte, A. Smith and D. Storch, Biodiversity scales from plots to biomes with a universal species-area curve, Ecology Letters 12 (2009), 789–797.

[Harte2011] J. Harte, Maximum Entropy and Ecology: A Theory of Abundance, Distribution, and Energetics, Oxford U. Press, Oxford, 2011.

[LH2013] M. Harper and C. Lee, Basic experiment planning via information metrics: the RoboMendel problem, arXiv:1210.4808 (2012).

[O2005] A. Ostling, Neutral theory tested by birds, Nature 436 (2005), 635.

[O2012] A. Ostling, Do fitness-equalizing tradeoffs lead to neutral communities?, Theoretical Ecology 5 (2012), 181–194.

[PS2012] D. Precup and S. Still, An information-theoretic approach to curiosity-driven reinforcement learning, Theory in Biosciences 131 (2012), 139–148.


Autocatalysis in Reaction Networks

11 October, 2013

guest post by Manoj Gopalkrishnan

Since this is my first time writing a blog post here, let me start with a word of introduction. I am a computer scientist at the Tata Institute of Fundamental Research, broadly interested in connections between Biology and Computer Science, with a particular interest in reaction networks. I first started thinking about them during my Ph.D. at the Laboratory for Molecular Science. My fascination with them has been predominantly mathematical. As a graduate student, I encountered an area with rich connections between combinatorics and dynamics, and surprisingly easy-to-state and compelling unsolved conjectures, and got hooked.

There is a story about Richard Feynman that he used to take bets with mathematicians. If any mathematician could make Feynman understand a mathematical statement, then Feynman would guess whether or not the statement was true. Of course, Feynman was in a habit of winning these bets, which allowed him to make the boast that mathematics, especially in its obsession for proof, was essentially irrelevant, since a relative novice like himself could after a moment’s thought guess at the truth of these mathematical statements. I have always felt Feynman’s claim to be unjust, but have often wondered what mathematical statement I would put to him so that his chances of winning were no better than random.

Today I want to tell you of a result about reaction networks that I have recently discovered with Abhishek Deshpande. The statement seems like a fine candidate to throw at Feynman because until we proved it, I would not have bet either way about its truth. Even after we obtained a short and elementary proof, I do not completely ‘see’ why it must be true. I am hoping some of you will be able to demystify it for me. So, I’m just going to introduce enough terms to be able to make the statement of our result, and let you think about how to prove it.

John and his colleagues have been talking about reaction networks as Petri nets in the network theory series on this blog. As discussed in part 2 of that series, a Petri net is a diagram like this:

Following John’s terminology, I will call the aqua squares ‘transitions’ and the yellow circles ‘species’. If we have some number #rabbit of rabbits and some number #wolf of wolves, we draw #rabbit many black dots called ‘tokens’ inside the yellow circle for rabbit, and #wolf tokens inside the yellow circle for wolf, like this:

Here #rabbit = 4 and #wolf = 3. The predation transition consumes one ‘rabbit’ token and one ‘wolf’ token, and produces two ‘wolf’ tokens, taking us here:

John explained in parts 2 and 3 how one can put rates on different transitions. For today I am only going to be concerned with ‘reachability:’ what token states are reachable from what other token states. John talked about this idea in part 25.

By a complex I will mean a population vector: a snapshot of the number of tokens in each species. In the example above, (#rabbit, #wolf) is a complex. If y, y' are two complexes, then we write

y \to y'

if we can get from y to y' by a single transition in our Petri net. For example, we just saw that

(4,3)\to (3,4)

via the predation transition.

Reachability, denoted \to^*, is the transitive closure of the relation \to. So y\to^* y' (read y' is reachable from y) iff there are complexes

y=y_0,y_1,y_2,\dots,y_k =y'

such that

y_0\to y_1\to\cdots\to y_{k-1}\to y_k.

For example, here (5,1) \to^* (1, 5) by repeated predation.

I am very interested in switches. After all, a computer is essentially a box of switches! You can build computers by connecting switches together. In fact, that’s how early computers like the Z3 were built. The CMOS gates at the heart of modern computers are essentially switches. By analogy, the study of switches in reaction networks may help us understand biochemical circuits.

A siphon is a set of species that is ‘switch-offable’. That is, if there are no tokens in the siphon states, then they will remain absent in future. Equivalently, the only reactions that can produce tokens in the siphon states are those that require tokens from the siphon states before they can fire. Note that no matter how many rabbits there are, if there are no wolves, there will continue to be no wolves. So {wolf} is a siphon. Similarly, {rabbit} is a siphon, as is the union {rabbit, wolf}. However, when Hydrogen and Oxygen form Water, {Water} is not a siphon.

For another example, consider this Petri net:

The set {HCl, NaCl} is a siphon. However, there is a conservation law: whenever an HCl token is destroyed, an NaCl token is created, so that #HCl + #NaCl is invariant. If both HCl and NaCl were present to begin with, the complexes where both are absent are not reachable. In this sense, this siphon is not ‘really’ switch-offable. As a first pass at capturing this idea, we will introduce the notion of ‘critical set’.

A conservation law is a linear expression involving numbers of tokens that is invariant under every transition in the Petri net. A conservation law is positive if all the coefficients are non-negative. A critical set of states is a set that does not contain the support of a positive conservation law.

For example, the support of the positive conservation law #HCl + #NaCl is {HCl, NaCl}, and hence no set containing this set is critical. Thus {HCl, NaCl} is a siphon, but not critical. On the other hand, the set {NaCl} is critical but not a siphon. {HCl} is a critical siphon. And in our other example, {Wolf, Rabbit} is a critical siphon.

Of particular interest to us will be minimal critical siphons, the minimal sets among critical siphons. Consider this example:

Here we have two transitions:

X \to 2Y

and

2X \to Y

The set \{X,Y\} is a critical siphon. But so is the smaller set \{X\}. So, \{X,Y\} is not minimal.

We define a self-replicable set to be a set A of species such that there exist complexes y and y' with y\to^* y' such that for all i \in A we have

y'_i > y_i

So, there are transitions that accomplish the job of creating more tokens for all the species in A. In other words: these species can ‘replicate themselves’.

We define a drainable set by changing the > to a <. So, there are transitions that accomplish the job of reducing the number of tokens for all the species in A. These species can ‘drain away’.

Now here comes the statement:

Every minimal critical siphon is either drainable or self-replicable!

We prove it in this paper:

• Abhishek Deshpande and Manoj Gopalkrishnan, Autocatalysis in reaction networks.

But first note that the statement becomes false if the critical siphon is not minimal. Look at this example again:

The set \{X,Y\} is a critical siphon. However \{X,Y\} is neither self-replicable (since every reaction destroys X) nor drainable (since every reaction produces Y). But we’ve already seen that \{X,Y\} is not minimal. It has a critical subsiphon, namely \{X\}. This one is minimal—and it obeys our theorem, because it is drainable.

Checking these statements is a good way to make sure you understand the concepts! I know I’ve introduced a lot of terminology here, and it takes a while to absorb.

Anyway: our proof that every minimal critical siphon is either drainable or self-replicable makes use of a fun result about matrices. Consider a real square matrix with a sign pattern like this:

\left( \begin{array}{cccc} <0 & >0 & \cdots & > 0 \\ >0 & <0 & \cdots &> 0 \\ \vdots & \vdots & <0 &> 0 \\ >0 & >0 & \cdots & <0 \end{array} \right)

If the matrix is full-rank then there is a positive linear combination of the rows of the matrix so that all the entries are nonzero and have the same sign. In fact, we prove something stronger in Theorem 5.9 of our paper. At first, we thought this statement about matrices should be equivalent to one of the many well-known alternative statements of Farkas’ lemma, like Gordan’s theorem.

However, we could not find a way to make this work, so we ended up proving it by a different technique. Later, my colleague Jaikumar Radhakrishnan came up with a clever proof that uses Farkas’ lemma twice. However, so far we have not obtained the stronger result in Theorem 5.9 with this proof technique.

My interest in the result that every minimal critical siphon is either drainable or self-replicable is not purely aesthetic (though aesthetics is a big part of it). There is a research community of folks who are thinking of reaction networks as a programming language, and synthesizing molecular systems that exhibit sophisticated dynamical behavior as per specification:

International Conference on DNA Computing and Molecular Programming.

Foundations of Nanoscience: Self-Assembled Architectures and Devices.

Molecular Programming Architectures, Abstractions, Algorithms and Applications.

Networks that exhibit some kind of catalytic behavior are a recurring theme among such systems, and even more so in biochemical circuits.

Here is an example of catalytic behavior:

A + C \to B + C

The ‘catalyst’ C helps transform A to B. In the absence of C, the reaction is turned off. Hence, catalysts are switches in chemical circuits! From this point of view, it is hardly surprising that they are required for the synthesis of complex behaviors.

In information processing, one needs amplification to make sure that a signal can propagate through a circuit without being overwhelmed by errors. Here is a chemical counterpart to such amplification:

A + C \to 2C

Here the catalyst C catalyzes its own production: it is an ‘autocatalyst’, or a self-replicating species. By analogy, autocatalysis is key for scaling synthetic molecular systems.

Our work deals with these notions on a network level. We generalize the notion of catalysis in two ways. First, we allow a catalyst to be a set of species instead of a single species; second, its absence can turn off a reaction pathway instead of a single reaction. We propose the notion of self-replicable siphons as a generalization of the notion of autocatalysis. In particular, ‘weakly reversible’ networks have critical siphons precisely when they exhibit autocatalytic behavior. I was led to this work when I noticed the manifestation of this last statement in many examples.

Another hope I have is that perhaps one can study the dynamics of each minimal critical siphon of a reaction network separately, and then somehow be able to answer interesting questions about the dynamics of the entire network, by stitching together what we know for each minimal critical siphon. On the synthesis side, perhaps this could lead to a programming language to synthesize a reaction network that will achieve a specified dynamics. If any of this works out, it would be really cool! I think of how abelian group theory (and more broadly, the theory of abelian categories, which includes categories of vector bundles) benefits from a fundamental theorem that lets you break a finite abelian group into parts that are easy to study—or how number theory benefits from a special case, the fundamental theorem of arithmetic. John has also pointed out that reaction networks are really presentations of symmetric monoidal categories, so perhaps this could point the way to a Fundamental Theorem for Symmetric Monoidal Categories.

And then there is the Global Attractor Conjecture, a
long-standing open problem concerning the long-term behavior of solutions to the rate equations. Now that is a whole story by itself, and will have to wait for another day.


Maximum Entropy and Ecology

21 February, 2013

I already talked about John Harte’s book on how to stop global warming. Since I’m trying to apply information theory and thermodynamics to ecology, I was also interested in this book of his:

John Harte, Maximum Entropy and Ecology, Oxford U. Press, Oxford, 2011.

There’s a lot in this book, and I haven’t absorbed it all, but let me try to briefly summarize his maximum entropy theory of ecology. This aims to be “a comprehensive, parsimonious, and testable theory of the distribution, abundance, and energetics of species across spatial scales”. One great thing is that he makes quantitative predictions using this theory and compares them to a lot of real-world data. But let me just tell you about the theory.

It’s heavily based on the principle of maximum entropy (MaxEnt for short), and there are two parts:

Two MaxEnt calculations are at the core of the theory: the first yields all the metrics that describe abundance and energy distributions, and the second describes the spatial scaling properties of species’ distributions.

Abundance and energy distributions

The first part of Harte’s theory is all about a conditional probability distribution

R(n,\epsilon | S_0, N_0, E_0)

which he calls the ecosystem structure function. Here:

S_0: the total number of species under consideration in some area.

N_0: the total number of individuals under consideration in that area.

E_0: the total rate of metabolic energy consumption of all these individuals.

Given this,

R(n,\epsilon | S_0, N_0, E_0) \, d \epsilon

is the probability that given S_0, N_0, E_0, if a species is picked from the collection of species, then it has n individuals, and if an individual is picked at random from that species, then its rate of metabolic energy consumption is in the interval (\epsilon, \epsilon + d \epsilon).

Here of course d \epsilon is ‘infinitesimal’, meaning that we take a limit where it goes to zero to make this idea precise (if we’re doing analytical work) or take it to be very small (if we’re estimating R from data).

I believe that when we ‘pick a species’ we’re treating them all as equally probable, not weighting them according to their number of individuals.

Clearly R obeys some constraints. First, since it’s a probability distribution, it obeys the normalization condition:

\displaystyle{ \sum_n \int d \epsilon \; R(n,\epsilon | S_0, N_0, E_0) = 1 }

Second, since the average number of individuals per species is N_0/S_0, we have:

\displaystyle{ \sum_n \int d \epsilon \; n R(n,\epsilon | S_0, N_0, E_0) = N_0 / S_0 }

Third, since the average over species of the total rate of metabolic energy consumption of individuals within the species is E_0/ S_0, we have:

\displaystyle{ \sum_n \int d \epsilon \; n \epsilon R(n,\epsilon | S_0, N_0, E_0) = E_0 / S_0 }

Harte’s theory is that R maximizes entropy subject to these three constraints. Here entropy is defined by

\displaystyle{ - \sum_n \int d \epsilon \; R(n,\epsilon | S_0, N_0, E_0) \ln(R(n,\epsilon | S_0, N_0, E_0)) }

Harte uses this theory to calculate R, and tests the results against data from about 20 ecosystems. For example, he predicts the abundance of species as a function of their rank, with rank 1 being the most abundant, rank 2 being the second most abundant, and so on. And he gets results like this:

The data here are from:

• Green, Harte, and Ostling’s work on a serpentine grassland,

• Luquillo’s work on a 10.24-hectare tropical forest, and

• Cocoli’s work on a 2-hectare wet tropical forest.

The fit looks good to me… but I should emphasize that I haven’t had time to study these matters in detail. For more, you can read this paper, at least if your institution subscribes to this journal:

• J. Harte, T. Zillio, E. Conlisk and A. Smith, Maximum entropy and the state-variable approach to macroecology, Ecology 89 (2008), 2700–2711.

Spatial abundance distribution

The second part of Harte’s theory is all about a conditional probability distribution

\Pi(n | A, n_0, A_0)

This is the probability that n individuals of a species are found in a region of area A given that it has n_0 individuals in a larger region of area A_0.

\Pi obeys two constraints. First, since it’s a probability distribution, it obeys the normalization condition:

\displaystyle{ \sum_n  \Pi(n | A, n_0, A_0) = 1 }

Second, since the mean value of n across regions of area A equals n_0 A/A_0, we have

\displaystyle{ \sum_n n \Pi(n | A, n_0, A_0) = n_0 A/A_0 }

Harte’s theory is that \Pi maximizes entropy subject to these two constraints. Here entropy is defined by

\displaystyle{- \sum_n  \Pi(n | A, n_0, A_0)\ln(\Pi(n | A, n_0, A_0)) }

Harte explains two approaches to use this idea to derive ‘scaling laws’ for how n varies with n. And again, he compares his predictions to real-world data, and get results that look good to my (amateur, hasty) eye!

I hope sometime I can dig deeper into this subject. Do you have any ideas, or knowledge about this stuff?


Follow

Get every new post delivered to your Inbox.

Join 2,846 other followers