## Abstracting evolutionary games in cancer

February 9, 2019 Leave a comment

As you can tell from browsing the mathematical oncology posts on TheEGG, somatic evolution is now recognized as a central force in the initiation, progression, treatment, and management of cancer. This has opened a new front in the proverbial war on cancer: focusing on the ecology and evolutionary biology of cancer. On this new front, we are starting to deploy new kinds of mathematical machinery like fitness landscapes and evolutionary games.

Recently, together with Peter Jeavons, I wrote a couple of thousand words on this new machinery for Russell Rockne’s upcoming mathematical oncology roadmap. Our central argument being — to continue the war metaphor — that with new machinery, we need new tactics.

Biologist often aim for reductive explanations, and mathematical modelers have tended to encourage this tactic by searching for mechanistic models. This is important work. But we also need to consider other tactics. Most notable, we need to look at the role that abstraction — both theoretical and empirical abstraction — can play in modeling and thinking about cancer.

The easiest way to share my vision for how we should approach this new tactic would be to throw a preprint up on BioRxiv or to wait for Rockne’s road map to eventually see print. Unfortunately, BioRxiv has a policy against views-like articles — as I was surprised to discover. And I am too impatient to wait for the eventual giant roadmap article.

Hence, I want to share some central parts in this blog post. This is basically an edited and slightly more focused version of our roadmap. Since, so far, game theory models have had more direct impact in oncology than fitness landscapes, I’ve focused this post exclusively on games.

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## Fitness distributions versus fitness as a summary statistic: algorithmic Darwinism and supply-driven evolution

March 2, 2019 by Artem Kaznatcheev 3 Comments

For simplicity, especially in the fitness landscape literature, fitness is often treated as a scalar — usually a real number. If our fitness landscape is on genotypes then each genotype has an associated scalar value of fitness. If our fitness landscape is on phenotypes then each phenotype has an associated scalar value of fitness.

But this is a little strange. After all, two organisms with the same genotype or phenotype don’t necessarily have the same number of offspring or other life outcomes. As such, we’re usually meant to interpret the value of fitness as the mean of some random variable like number of children. But is the mean the right summary statistic to use? And if it is then which mean: arithmetic or geometric or some other?

One way around this is to simply not use a summary statistic, and instead treat fitness as a random variable with a corresponding distribution. For many developmental biologists, this would still be a simplification since it ignores many other aspects of life-histories — especially related to reproductive timing. But it is certainly an interesting starting point. And one that I don’t see pursued enough in the fitness landscape literature.

The downside is that it makes an already pretty vague and unwieldy model — i.e. the fitness landscape — even less precise and even more unwieldy. As such, we should pursue this generalization only if it brings us something concrete and useful. In this post I want to discuss two aspects of this: better integration of evolution with computational learning theory and thinking about supply driven evolution (i.e. arrival of the fittest). In the process, I’ll be drawing heavily on the thoughts of Leslie Valiant and Julian Z. Xue.

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Filed under Commentary, Models, Preliminary Tagged with evolution, fitness landscapes, fitness ontology, Leslie Valiant, machine learning