In our new CIHR proposal we're going to propose to gather the experimental information needed to make a predictive model of genetic exchange by transformation in the respiratory tract. I've been trying to lay out the Research Plan by describing the things we want to find out. But I realized last night that it might be better to start by describing the predictive model we want to generate, and let its requirements determine what we propose to find out.
That was when I also realized that I have no idea what form the model should take! That is, what would be the input information, and what would be the output. Let's see if I can do better this morning.
Of course, we don't need to have just one model. Several different models might be appropriate, to address different questions. For example, given two H. influenzae genome sequences, what are the relative probabilities of different recombination events? Of course we couldn't evaluate ALL the possible events, but we could tag the most likely and least likely. So we'd want to be able to scan the genome sequences of potential donors and flag the segments most likely and least likely to be taken up by competent cells. And we'd want to scan the genome sequences of potential recipients, flagging the segments most likely and least likely to undergo homologous recombination.
We could do this a different way. For each potential donor genome, we would evaluate the probability that a given segment would be taken up as a DNA fragment by competent cells. Then, for the other genome, we'd calculate the probabilities that different parts of this fragment would be recombined into the recipient genome.
Or we could evaluate a pool of DNA sequences with different proportions from different strains or species, again tagging the segments most likely to be taken up, and the effects of changing the proportions from different sources. And we could consider a population of possible recipients, consisting of strains with different levels of competence and present in different proportions.
OK, I think the post-doc and I are going to spend some time today working on this at the whiteboards in the hall.
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