Repeat with data samples, add noise and try to fit different models to the sampled occupancy landscape
- Oliver Hofmann
Used synthetic data, including experimental noise, then forgot the algorithm to generate the data and used the previously described models.
- Roland Krause
Exponential function shows a good correlation in five-fold cross-validation, with the model incorporating the interaction outperforming the ones without.
- Roland Krause
Are the interactions relevant in vivo and in vitro?
- Roland Krause
For an in vitro validation the Exp, Step functions work better than the no cooperativity model
- Oliver Hofmann
Interactions are also important using in vivo data, data from several chromosomes and different organisms (yeast and C. elegans) show similar results.
- Roland Krause
The interesting part -- biological basis for this preference?
- Oliver Hofmann
The in vitro system consists of nucleosomes and DNA only.
- Roland Krause
shorter length may allow for interaction of nucleosomes, energetically favoring their shift from otherwise better binding positions
- Oliver Hofmann
Hypothesis: electrostatic interaction between nucleosomes, which has been described previously but not shown in the data.
- Roland Krause
# Surprised that the very model was not presented in the talk.
- Roland Krause
# Wonder whether there is a difference between promoters, other nucleosome covered regions (or other genomic subsets); with the role nucleosome displacement plays in regulation I'd expect some shift
- Oliver Hofmann
Q: When you started motivating the model, there was a peak at 10 but the sample data did not have that.[?] A: These are effects of histone H1, which are not modeled. There are a lot of question marks about the role of H1 in yeast. The interaction that we modeled are global and can occur anywhere on the DNA. More complex model would incorporate additional local effects, e.g. other factors.
- Roland Krause
Q. Have you finished the model for the higher eukaryotes: A The model is independent of the organism. There might be differences, although this is debated. Differnces between yeast and human are known.
- Roland Krause