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).

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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.

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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.

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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.

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