Cataloging a sparse year of blogging: IMO workshop and preprints

Happy 2018!

With 2017 finally behind us, TheEGG enters its 8th calendar year. This past year has been a slow one for the blog, with only 10 new articles and two posts cataloguing 2016 (on cancer and on more theoretical aspects of evolution and general modelling). Half the months were barren: I posted nothing in March, April, May, July, August, September; and only October and November saw more than one post. But those two months of activity were good. We saw the list of TheEGG authors joined by David Robert Grimes, Vincent Cannataro, and Matthew Wicker; plus the return of Robert Vander Velde.

If you’re keeping score at home, this means that I only wrote six new articles last year.

As in the past, I want to start the new year by summarizing the old.

Read more of this post


Replicator dynamics and the simplex as a vector space

Over the years of TheEGG, I’ve chronicled a number of nice properties of the replicator equation and its wide range of applications. From a theoretical perspective, I showed how the differential version can serve as the generator for the action that is the finite difference version of replicator dynamics. And how measurements of replicator dynamics can correspond to log-odds. From an application perspective, I talked about how replicator dynamics can be realized in many different ways. This includes a correspondance to idealized replating experiments and a representation of populations growing toward carrying capacity via fictitious free-space strategies. These fictitious strategies are made apparent by using a trick to factor and nest the replicator dynamics. The same trick can also help us to use the symmetries of the fitness functions for dimensionality reduction and to prove closed orbits in the dynamics. And, of course, I discussed countless heuristic models and some abductions that use replicator dynamics.

But whenever some object becomes so familiar and easy to handle, I get worried that I am missing out on some more foundational and simple structure underlying it. In the case of replicator dynamics, Tom Leinster’s post last year on the n-Category Cafe pointed me to the simple structure that I was missing: the vector space structure of the simplex. This allows us to use linear algebra — the friendliest tool in the mathematician’s toolbox — in a new way to better understand evolutionary dynamics.

A 2-simplex with some of its 1-dimensional linear subspaces drawn by Greg Egan.

Given my interest in operationalization of replicator dynamics, I will use some of the terminology and order of presentation from Aitchison’s (1986) statistical analysis of compositional data. We will see that a number of operations that we define will have clear experimental and evolutionary interpretations.

I can’t draw any real conclusions from this, but I found it worth jotting down for later reference. If you can think of a way to make these observations useful then please let me know.

Read more of this post

Dark selection from spatial cytokine signaling networks

Greetings, Theory, Evolution, and Games Group! It’s a pleasure to be on the other side of the keyboard today. Many thanks to Artem for the invite to write about some of our recent work and the opportunity to introduce myself via this post. I do a bit of blogging of my own over at — mostly about neat science I stumble over while figuring out my way.

I’m a biologist. I study the evolutionary dynamics within somatic tissue, or, how mutations occur, compete, accumulate, and persist in our tissues, and how these dynamics manifest as aging and cancer (Cannataro et al., 2017a). I also study the evolutionary dynamics within tumors, and the evolution of resistance to targeted therapy (Cannataro et al., 2017b).

In November 2016 I attended the Integrated Mathematical Oncology Workshop on resistance, a workweek-long intensive competitive workshop where winners receive hard-earned $$ for research, and found myself placed in #teamOrange along with Artem. In my experience at said workshop (attended 2015 and 2016), things usually pan out like this: teams of a dozen or so members are assembled by the workshop organizers, insuring a healthy mix of background-education heterogeneity among groups, and then after the groups decide on a project they devise distinct but intersecting approaches to tackle the problem at hand. I bounced around a bit early on within #teamOrange contributing to our project where I could, and when the need for a spatially explicit model of cytokine diffusion and cell response came up I jumped at the opportunity to lead that endeavor. I had created spatially explicit cellular models before — such as a model of cell replacement in the intestinal crypt (Cannataro et al., 2016) — but never one that incorporated the diffusion or spread of some agent through the space. That seemed like a pretty nifty tool to add to my research kit. Fortunately, computational modeler extraordinaire David Basanta was on our team to teach me about modeling diffusion (thanks David!).

Below is a short overview of the model we devised.

Read more of this post

Ratcheting and the Gillespie algorithm for dark selection

In Artem’s previous post about the IMO workshop he suggests that “[s]ince we are forced to move from the genetic to the epigenetic level of description, it becomes important to suggest a plausible mechanism for heritable epigenetic effects. We need to find a stochastic ratcheted phenotypic switch among the pathways of the CMML cells.” Here I’ll go into more detail about modeling this ratcheting and how to go about identifying the mechanism. We can think of this as a potential implementation of the TYK bypass in the JAK-STAT pathway described experimentally by Koppikar et al. (2012). However, I won’t go into the specifics of exact molecules, keeping to the abstract essence.

After David Robert Grime’s post on oxygen use, this is the third entry in our series on dark selection in chronic myelomonocytic leukemia (CMML). We have posted a preprint (Kaznatcheev et al., 2017) on our project to BioRxiv and section 3.1 therein follows this post closely.

Read more of this post

Identifying therapy targets & evolutionary potentials in ovarian cancer

For those of us attending the 7th annual Integrated Mathematical Oncology workshop (IMO7) at the Moffitt Cancer Center in Tampa, this week was a gruelling yet exciting set of four near-all-nighters. Participants were grouped into five teams and were tasked with coming up with a new model to elucidate a facet of a particular type of cancer. With $50k on the line and enthusiasm for creating evolutionary models, Team Orange (the wonderful team I had the privilege of being a part of) set out to understand something new about ovarian cancer. In this post, I will outline my perspective on the initial model we came up with over the past week.

Read more of this post

Ontology of player & evolutionary game in reductive vs effective theory

In my views of game theory, I largely follow Ariel Rubinstein: game theory is a set of fables. A collection of heuristic models that helps us structure how we make sense of and communicate about the world. Evolutionary game theory was born of classic game theory theory through a series of analogies. These analogies are either generalizations or restrictions of the theory depending on if you’re thinking about the stories or the mathematics. Given this heuristic genealogy of the field — and my enjoyment of heuristic models — I usually do not worry too much about what exactly certain ontic terms like strategy, player, or game really mean or refer to. I am usually happy to leave these terms ambiguous so that they can motivate different readers to have different interpretations and subsequently push for different models of different experiments. I think it is essential for heuristic theories to foster this diverse creativity. Anything goes.

However, not everyone agrees with Ariel Rubinstein and me; some people think that EGT isn’t “just” heuristics. In fact, more recently, I have also shifted some of my uses of EGT from heuristics to abductions. When this happens, it is no longer acceptable for researchers to be willy-nilly with fundamental objects of the theory: strategies, players, and games.

The biggest culprit is the player. In particular, a lot of confusion stems from saying that “cells are players”. In this post, I’d like to explore two of the possible positions on what constitutes players and evolutionary games.

Read more of this post

Hackathons and a brief history of mathematical oncology

It was Friday — two in the morning. And I was busy fine-tuning a model in Mathematica and editing slides for our presentation. My team and I had been running on coffee and snacks all week. Most of us had met each other for the first time on Monday, got an inkling of the problem space we’d be working on, brainstormed, and hacked together a number of equations and a few chunks of code to prototype a solution. In seven hours, we would have to submit our presentation to the judges. Fifty thousand dollars in start-up funding was on the line.

A classic hackathon, except for one key difference: my team wasn’t just the usual mathematicians, programmers, computer & physical scientists. Some of the key members were biologists and clinicians specializing in blood cancers. And we weren’t prototyping a new app. We were trying to predict the risk of relapse for patients with chronic myeloid leukemia, who had stopped receiving imatinib. This was 2013 and I was at the 3rd annual integrated mathematical oncology workshop. It was one of my first exposures to using mathematical and computational tools to study cancer; the field of mathematical oncology.

As you can tell from other posts on TheEGG, I’ve continued thinking about and working on mathematical oncology. The workshops have also continued. The 7th annual IMO workshop — focused on stroma this year — is starting right now. If you’re not in Tampa then you can follow #MoffittIMO on twitter.

Since I’m not attending in person this year, I thought I’d provide a broad overview based on an article I wrote for Oxford Computer Science’s InSPIRED Research (see pg. 20-1 of this pdf for the original) and a paper by Helen Byrne (2010).

Read more of this post

Oxygen fueling dark selection in the bone marrow

While November 2016 might be remembered for the inauspicious political upset likely to leave future historians as confused as we are, a more positive event transpired in tandem – the 6th Integrated Mathematical Oncology (IMO) Workshop. I was honoured to take part as a member of Team Orange, where we were tasked with investigating the emergence of treatment resistance in chronic myelomonocytic leukemia (CMML).

Unlike many other cancers where the evolution of resistance to treatment is well understood, CMML is something of an enigma as the efficacy of treatment flounders even though the standard treatment doesn’t directly impinge upon tumour cells themselves.  This raises a whole host of questions, and Artem has already eloquently laid out both why this question captivated us, and the combined approach we took to probing it. In this blog post, I’ll focus on exploring one of our mechanistic hypotheses – the potential role of oxygen in treatment resistance.

Read more of this post

Poor reasons for preprints & post-publication peer-review

Last week, I revived the blog with some reflections on open science. In particular, I went into the case for pre-prints and the problem with the academic publishing system. This week, I want to continue this thread by examining three common arguments for preprints: speed, feedback, and public access. I think that these arguments are often motivated in the wrong way. In their standard presentation, they are bad arguments for a good idea. By pointing out these perceived shortcoming, I hope that we can develop more convincing arguments for preprints. Or maybe methods of publication that are even better than the current approach to preprints.

These thoughts are not completely formed, and I am eager to refine them in follow up posts. As it stand, this is more of a hastily written rant.

Read more of this post

Preprints and a problem with academic publishing

This is the 250th post on the Theory, Evolutionary, and Games Group Blog. And although my posting pace has slowed in recent months, I see this as a milestone along the continuing road of open science. And I want to take this post as an opportunity to make some comments on open science.

To get this far, I’ve relied on a lot of help and encouragement. Both directly from all the wonderful guest posts and comments, and indirectly from general recognition. Most recently, this has taken the form of the Canadian blogging and science outreach network Science Borealis recognized us as one of the top 12 science blogs in Canada.

Given this connection, it is natural to also view me as an ally of other movements associated with open science; like, (1) preprints and (2) post-publication peer-review (PPPR). To some extent, I do support both of these activities. First, I regularly post my papers to ArXiv & BioRxiv. Just in the two preceeding months, I’ve put out a paper on the complexity of evolutionary equilibria and joint work on how fibroblasts and alectinib switch the games that cancers play. Another will follow later this month based on our project during the 2016 IMO Workshop. And I’ve been doing this for a while: the first draft of my evolutionary equilibria paper, for example, is older than BioRxiv — which only launched in November 2013. More than 20 years after physicists, mathematicians, and computer scientists started using ArXiv.

Second, some might think of my blog posts as PPPRs. For example. occasionally I try to write detailed comments on preprints and published papers. For example, my post on fusion and sex in proto-cells commenting on a preprint by Sam Sinai, Jason Olejarz and their colleagues. Finally, I am impressed and made happy by the now iconic graphic on the growth of preprints in biology.

But that doesn’t mean I find these ideas to be beyond criticism, and — more importantly — it doesn’t mean that there aren’t poor reasons for supporting preprints and PPPR.

Recently, I’ve seen a number of articles and tweets written on this topic both for and against (or neutral toward) pre-prints and for PPPR. Even Nature is telling us to embrace preprints. In the coming series of posts, I want to share some of my reflections on the case for preprints, and also argue that there isn’t anything all that revolutionary or transformative in them. If we want progress then we should instead think in terms of working papers. And as for post-publications peer review — instead, we should promote a culture of commentaries, glosses, and literature review/synthesis.

Currently, we do not publish papers to share ideas. We have ideas just to publish papers. And we need to change this aspect academic culture.

In this post, I will sketch some of the problems with academic publishing. Problems that I think any model of sharing results will have to address.

Read more of this post