I am a model, you know what I mean (and I do my little turn on the catwork)

I recently started a project to model certain signalling pathways in our favourite macrophage cell and it's been an eye-opening experience. Once its complete, we will learn volumes about the role of cholesterol in the immune system. But at this stage, just working out the angles has been fascinating. The challenges don't come from the directions you might think.

At first, I thought they'd be computational. People have been modelling pathways for years, so I reasoned that all the straight forward work must have been done. In established fields, the new challenges come from the projects that push computing power to its limit, so I assumed that ours must have been computationally complex. But it turns out that this isn't the case. Few trusted models of signalling pathways exist and those that do are quite simple, so they are pretty straight forward to simulate.

If the challenges weren't computational, then I thought they might surround model validity. A living cell is a complex beast. So much is happening inside that to isolate one pathway, without including any others, is a risky business. Doing so might invalidate the results of the model. Well, in some cases this might be true, but the real problems occur before we get a chance to see.

The true obstacles aren't computation or simplification, they're come from something much more old-fashioned. People.

When you dig into the papers, you find that genes and proteins have been given a bunch of different names by different research groups and each name can have a bunch of different abbreviations. This makes them hard to cross reference. The papers aren't stored in any single central database, but across many databases and they aren't catalogued or indexed in a friendly way. This makes them hard to find. The papers rarely systematically explore pathways, so the proteins they describe tend to freely appear and disappear as they are needed. This makes their behaviour hard to describe.

Combined, these problems make modelling hard and it takes a strong will and plenty of sweat to pull a model out of the mire. For this reason alone, pathway modellers have gone up in my estimation. They've earned my respect.