Sunday, December 15, 2013

Handling collaborative projects in the age of the cloud - how to manage without spending any money!

As a clinician cum scientist, I am almost always involved in collaborations with multi-disciplinary groups.  And, as an american who has done some training in the UK, many of those groups are NOWHERE REMOTELY NEAR one another.  To keep myself, and my collaborators sane, I've been constantly experimenting with different combinations of cloud based repositories so that we can all work on things together.

So, I started out with +Dropbox by itself, but quickly found that, without spending money, I quickly filled up my allotted space.  Even after totally maxing out the freebie upgrades (I think I have like 35Gb or something thanks to some promo at Oxford, referring everyone I know and being a shameless social media promoter - every Mb counts!), I still am limited.  So I added +SugarSync for my personal files, to clear off dropbox and leave it for just collaboration.  Well, that filled up pretty quick too, and as I haven't found sugarsync to be as easy to navigate as dropbox, I haven't worked as hard to maximize my space there.  I muddled along with these two but still struggled with things like version control and the desire for contemporaneous editing.  Which led to...

Google drive and google docs.  So, with google drive, you get 25Gb or something, but I started to get confused as to where things were.  When I wanted to collaborate real time though, I was stuck, as google docs was really the best thing going (and still is, for many things).  However, in the last few months, I discovered +writeLaTeX, which has really changed the way I do business.  This is a (mostly) free service (I haven't hit the wall yet, and it is pretty big considering that you don't store data there really) in which you can create, manage and edit LaTeX documents with as many people as you like. For me, as a mathematical biologist, this was great - so long as my collaborators were also theorists who were tex-savvy.  I first used it doing a little hack-a-thon with some friends that I blogged about before. Recently though, as in, in the last few days, they have added a Rich Text formatting layer which, I think, will change everything again.  No longer will I have to give the link to a document to my biological/clinical collaborator with the caveat 'just ignore everything that isn't text - squint a bit if you have to'.  Now, they can just go ahead and edit away just like they are in word or whatever, but I can come in behind and have the full functionality of LaTeX.  So that aspect seems solved.

**note - I LOVE writelatex, and you should check it out... and if you do, use this code and I get 50MB more space. **

The only issue left for me is, now that I'm cranking TONS of simulations in (what I hope is) the final push toward this whole PhD thing, how to work on a DATA-HOG of a project on two computers (I can't stay at work late because I want to go home to my super sweet little kids, but then I DO want to work after they go to bed without driving back to work) or to share this with someone else.  I thought, at first, that I'd just clear out my dropbox a bit, and try to be parsimonious with what I saved...  but, as the output for my simulations is \mathcal{O} 30Gb/simulation, this quickly became unfeasible.  Enter bittorrentsync - my saviour.  This little gem (free) lets you have a synced drive on as many computers as you like.  The freeing move here is that there is no cloud interaction, so there is NO SPACE LIMITATION.  (There is also no auto-backup for the same reason... but this is obviated if you use Time Machine or something similar).  All you do is download the software (a couple Mb's) and then, to set up a shared directory, it generates a 'secret' which you share with whomever you want to share.  The secret is a massive string of letters/numbers that is autogenerated - and I bet even the guy at would approve.

So, now I'm set and I don't have to think too hard.  I also don't forsee ever having to spend any money (until maybe I have a lab or my own and lots of people, but by then - if that time ever comes - I will have grant money to spend on such things...  ?).

Summary: I use dropbox for shared/travelling talks, figures, syncing my papers library, shared simple code (matlab, etc).  I use sugarsync for my personal documents (though I might phase this out...). I use writelatex for (now and going forward) ALL papers I write and bittorrent sync for shared working directories (also home/office syncing of working directories).

As an aside, dropbox has a cool feature - since everyone can modify things at will, they have a nice cloud backup system, which includes who the last person to interact with a document was, so in case your supervisor starts randomly deleting hunks of your thesis, you can call them on it - not naming any names...  +Alexander Anderson :)

To be fair, I don't think Sandy actually deleted this stuff... and I was able to recover it, but it was pretty funny :)

Monday, December 9, 2013

Guest post on the Oxford Centre for Maths Biology Blog

I wrote a post for my group's new blog on the importance of #preprints in science, and specifically on the new #bioRxiv.  Head on over and check it out:

Thursday, December 5, 2013

Investigating the effects of microenvironmental perturbation on a stem driven tumor

I've been interested in the cancer stem cell hypothesis for some time, a subject that my colleague +Heiko Enderling has been thinking about and modeling for some time (list of his pubs here). I first became interested in this concept before I became a DPhil student and member of the Integrated Mathematical Oncology group, when I was a clinical resident in radiation oncology at the Moffitt Cancer Center.  One of the first papers that I saw that truly scared me was a paper by Tamura and colleagues (abstract) that showed that recurrent glioblastomas had a significant increase in CD-133 staining (a stain commonly associated with stemness in this cancer and others), and that this increase is correlated with (maybe causes, jury yet out) an increase in aggressiveness of the recurrent tumor and a decrease in its sensitivity to treatment.

The standard rationale for the latter is that these special 'stem cells' have a higher intrinsic resistance to radiation therapy (which I don't argue), but I subsequently wrote down a series of simple (some might say Noddy) ODE models which suggested, at least to me, that there might also be a stem promoting effect of radiation.  Since then, I have found that this effect has been shown in breast cancer, and further, that there have been a number of microenvironmental perturbations that have been shown to do the same thing, though only in a qualitative way - many of these articles have had my collaborator, +Anita Hjelmeland as a co-author, and I talked about them quite a bit in a previous blog post on our recent R-01 submission.

When I first started on this problem from the theoretical standpoint, it was with ODE models, as I mentioned.  But since then, +David Basanta and +Alexander Anderson and I have worked to build a cellular automaton model of a stem-driven tumor which included blood vessels as sources of oxygen. We built this simple model to test if there were some sort of intrinsic/emergent change in the resultant tissue phenotype when the overall levels of oxygen supplied to it went down (when we reduced the density of the vessels).  Below you can see the schematic of our model system.  On the left is the canonical Cancer Stem Cell hypothesis (which I have major issues with...  more to come in a few weeks I hope) and on the right there is our CA model rules.

After much simulation and effort we found... in short, that no, there is not. Our initial, negative results, were frustrating, but after discussions with +Anita Hjelmeland and Prakash Chinnaiyan (a biologist and clinician, respectively) we found that the model was telling us more...  while we found little qualitative effect when we changed the vascular density, changing the instrinsic stem behavior parameters in the presence of a minimalistic environment revealed that there were only three major meta-phentypic behaviors possible: extinction, dormancy (homeostasis) and overgrowth as seen below.

Our frustration at not seeing the emergence of greater stem-fraction upon lowering the oxygen levels however, led to the rather obvious (in retrospect) conclusion that only through a modification of the symmetric division rate of the stem cells (modified by hypoxia) could this effect be recapitulated. Interestingly, this is a conclusion we had come to in the past using a simpler model system (ODEs) but it was never convincing (though there is a nice piece in J Theoretical Biology which gave me some confidence... here).  Initial testing of this hypothesis, by modification of the CA rules to include this change are striking - surrounding the area of hypoxia, we have an emergent stem cell niche.

Stem cells (red) emerge in areas surrounding necrosis (white/center) when the CA rules allow biased symmetric division in the presence of moderate hypoxia (right).

We have just begun exploring this phenomenon, and indeed there is quite a bit of work to do, both theoretically and experimentally, to validate and better characterize what is going on - so that's why we wrote an R-01.

Anyways, if you want more details, you can read the paper on the bioRxiv now, or in a few days on PLoS Computational Biology where it has been accepted and is nearing publication.  We've also made the baseline code freely available on sourceforge here.

If you have comments on the paper itself, please leave them on the bioRxiv site so anyone can see them (or wait to put them on the PLoS CB site). Ok, back to work.