Skip to main content

T:World 2: Why did the development take ages?

 It is an unfortunate fact that this project went on for quite long. One could trace the roots to what I described in my ToR-ORd blog on RyRs and calcium handling, saying how we could not achieve everything we wanted. I hate to be beaten by a mystery and of course wanted to revisit this problem if I could (except within few weeks of finalizing ToR-ORd, while the arguably healthier mindset of “I’ll never make another model” lasted). The blog was published in Dec 2019, and the first unsuccessful forays into more realistic calcium handling we have taken might have even taken place in 2018. (I’m not the worst in this in our household though, my wife’s major project – and amazing success – took 8 years to finish)

The scale of development was simply on another level compared to the prior ToR-ORd. There were many more and larger conceptual decisions, more situations of “OK, I have NO idea what to do about this”. For each development step (testing a new idea, running a genetic algorithm, analysing something, etc.), I create a numbered script, so I can track and revisit progress – there were over 900 of those scripts, and countless checks too small to be assigned a number. I kept numbering distinct models, using major and minor version numbers. The mostly final model we had was version 11.3.2. During the development, there were versions such as 5.7.3.5.4 or 8.9.6.5. There was a lot to explore, understand, parametrize and develop. Below are described several choices we had to make, that will give some insight into why the T-World making was quite tricky. They start with very high-level conceptual decisions related to the philosophy of calcium handling, finishing with what could be seen as a minor point (voltage dependence of the Na-K pump).

Comments

Post a Comment

Popular posts from this blog

Several tips on junior fellowship applications

It turns out I was fortunate enough to receive the Sir Henry Fellowship from Wellcome Trust. This is a four-year international fellowship that will allow me to spend some time at UC Davis, California as well as University of Oxford, focusing on interdisciplinary investigation of diabetic arrhythmogenesis. It was certainly an interesting and person-developing experience (obviously viewed more favourably given the outcome). I had the advantage of working under/with highly successful people who gave me valuable advice about the process and requirements. I am quite sure that  I would not have gotten the fellowship without the support of Profs. Manuela Zaccolo, Blanca Rodriguez, and Don Bers, to whom I'm deeply grateful. However, not everyone has such nice and investing-in-you supervisors and beyond very generic advice, there is very little information on the internet on what the process of applying for junior fellowship entails [1]. The aim of this text is to share some findings I ma...
Post a Comment
Read more

Writing a book punk-style

  Our book on statistics is coming out, after three years of work. The number of questions on “how did this happen?” and “how is it to write a book” I’ve been getting recently warrants a blog post with a bit of an early post-mortem – here it is! How did this happen is answered quite easily: I’ve often advised colleagues on statistics, and they frequently asked, “which book should I get”? Despite suggesting some textbooks, colleagues generally found them too long, and/or complicated and/or missing important content while containing plenty of lower-relevance information. Over time, I understood why existing books do not quite meet their needs. Examples of problems include:   Length over 500 pages.  This is completely fine for people who  want  to learn statistics in a certain depth. But most researchers in life sciences are busy with their own research and do not have training and priority for an in-depth d...
Post a Comment
Read more

Making a Model: Part 0 - Introduction

Welcome, dear reader. This is the start of a short series of blog posts aimed at providing some insight into the process of development of a computational model of a cell. The type of the model we’ll focus at is one which simulates the development of ionic concentrations and behavior of ionic currents and fluxes over time (probably most relevant for excitable cells such as cardiomyocytes or neurons). I'm hoping that tips and observations in this series will be of use to graduate students and researchers who are interested in computer simulations. While the posts are about the development of human ventricular cardiomyocyte model ToR-ORd ( https://elifesciences.org/articles/48890 ), I mostly try to focus on general observations (usually those I wish I knew about when I started). I decided to write up the topics in the form of blog, given that scientific publications tend to have a somewhat rigid format, and tend to focus at what is done, how, and what it means, rather than at ...
Post a Comment
Read more