Minimal models for explaining unbounded increase in fitness

On a prior version of my paper on computational complexity as an ultimate constraint, Hemachander Subramanian made a good comment and question:

Nice analysis Artem! If we think of the fitness as a function of genes, interactions between two genes, and interactions between three genes and so on, your analysis using epistasis takes into account only the interactions (second order and more). The presence or absence of the genes themselves (first order) can change the landscape itself, though. Evolution might be able to play the game of standing still as the landscape around it changes until a species is “stabilized” by finding itself in a peak. The question is would traversing these time-dependent landscapes for optima is still uncomputable?

And although I responded to his comment in the bioRxiv Disqus thread, it seems that comments are version locked and so you cannot see Hema’s comment anymore on the newest version. As such, I wanted to share my response on the blog and expand a bit on it.

Mostly this will be an incomplete argument for why biologists should care about worst-case analysis. I’ll have to expand on it more in the future.

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The wei wu wei of evolutionary oncology

The world was disordered, rains would come and the rivers would flood. No one knew when. When it rained, plants would grow, but no one knew which were fit to eat and which were poisonous. Sickness was rife. Life was precarious.

The philosopher-king Yu dredged the rivers, cleaned them so they would flow into the sea. Only then were the people of the Middle Kingdom able to grow the five grains to obtain food.

Generations later, Bai Gui — the prime minister of Wei — boasted to Mengzi: “my management of the water is superior to that of Yu.”

Mengzi responded: “You are wrong. Yu’s method was based on the way of the water. It is why Yu used the four seas as receptacles. But you are using the neighbouring states as receptacles. When water goes contrary to its course, we call if overflowing. Overflowing means flooding water, something that a humane man detests… As for Yu moving the waters, he moved them without interference.”

Although Yu made changes to the environment by digging channels, he did so after understanding how the water flowed and moved naturally. He did so with knowledge of the Way. Yu’s management of water was superior to Bai Gui’s because Yu’s approach was in accordance with the Way. This is what evolutionary oncology seeks to achieve with cancer treatment. By understanding how the dynamics of somatic evolution drive tumour growth, we hope to change the selective pressures in accordance with this knowledge to manage or cure the disease.

Mathtimidation by analytic solution vs curse of computing by simulation

Recently, I was chatting with Patrick Ellsworth about the merits of simulation vs analytic solutions in evolutionary game theory. As you might expect from my old posts on the curse of computing, and my enjoyment of classifying games into dynamic regimes, I started with my typical argument against simulations. However, as I searched for a positive argument for analytic solutions of games, I realized that I didn’t have a good one. Instead, I arrived at another negative argument — this time against analytic solutions of heuristic models.

Hopefully this curmudgeoning comes as no surprise by now.

But it did leave me in a rather confused state.

Given that TheEGG is meant as a place to share such confusions, I want to use this post to set the stage for the simulation vs analytic debate in EGT and then rehearse my arguments. I hope that, dear reader, you will then help resolve the confusion.

First, for context, I’ll share my own journey from simulations to analytic approaches. You can see a visual sketch of it above. Second, I’ll present an argument against simulations — at least as I framed that argument around the time I arrived at Moffitt. Third, I’ll present the new argument against analytic approaches. At the end — as is often the case — there will be no resolution.

Methods and morals for mathematical modeling

About a year ago, Vincent Cannataro emailed me asking about any resources that I might have on the philosophy and etiquette of mathematical modeling and inference. As regular readers of TheEGG know, this topic fascinates me. But as I was writing a reply to Vincent, I realized that I don’t have a single post that could serve as an entry point to my musings on the topic. Instead, I ended up sending him an annotated list of eleven links and a couple of book recommendations. As I scrambled for a post for this week, I realized that such an analytic linkdex should exist on TheEGG. So, in case others have interests similar to Vincent and me, I thought that it might be good to put together in one place some of the resources about metamodeling and related philosophy available on this blog.

This is not an exhaustive list, but it might still be relatively exhausting to read.

I’ve expanded slightly past the original 11 links (to 14) to highlight some more recent posts. The free association of the posts is structured slightly, with three sections: (1) classifying mathematical models, (2) pros and cons of computational models, and (3) ethics of models.