Bayesian Inference of transcription factor activity - an application to the fission yeast cell cycle
Description
When modeling genetic regulatory interactions, it is often assumed that the
mRNA expression of a transcription factor is a reliable proxy for the regulatory
activity of that transcription factor. There are many examples where this
assumption does not hold due to post-transcriptional and translational modifications
of the transcription factor protein. As true transcription factor activity is
very difficult to measure, methods to infer it are becoming increasingly common
and it is likely that will become increasingly important when building models
of regulatory interactions.
Previously, we have shown how Bayesian techniques, particularly Markov-
Chain Monte-Carlo based sampling, can enable us to make inferences regarding
the activity of transcription factors based on the transcript levels of their targets.
However, in that work, we only looked at simple regulatory interactions
where one transcription factor acted individually on a set of target genes. In this
work, we investigate extending this model to the more general (and common)
case of multiple transcription factors working together.
As an example application, we use data from a small regulatory network
from the fission yeast cell cycle in which several transcription factors are known
to work together to produce the desired response, and for which plentiful experimental
data are available.
| Slides | |
| 0:00 | Towards Bayesian inference in multiple-input motifs |
| 0:09 | Overview |
| 0:37 | Previously.....TFA inference in SIMs |
| 2:17 | G/M2 Transition in fission yeast - part 1 |
| 3:50 | G/M2 Transition in fission yeast - part 2 |
| 4:10 | Competitive transcription factors |
| 5:26 | mRNA production |
| 7:13 | Stochastic Quasi-Steady-State assumption - part 1 |
| 7:46 | mRNA production |
| 7:50 | Stochastic Quasi-Steady-State assumption - part 1 |
| 8:23 | mRNA production |
| 8:45 | Stochastic Quasi-Steady-State assumption - part 1 |
| 9:10 | Stochastic Quasi-Steady-State assumption - part 2 |
| 10:25 | Competitive transcription factors |
| 11:25 | Examples - how good is the approximation? - part 1 |
| 12:26 | Examples - how good is the approximation? - part 2 |
| 12:54 | Example - inference - part 1 |
| 14:20 | Example - inference - part 2 |
| 14:50 | Conclusions and Future work |
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