Not isolated, but still insulated : switch-like transitions modularize biological networks
Abstract/Contents
- Abstract
- Cellular decisions are outputs of computations performed by complex genetic networks of interconnected protein, RNA, and DNA sequence elements that are difficult to comprehensively analyze. One way to study the principles underlying these computations has been to examine the dynamics of smaller sub-networks, known as network motifs. However, it is not clear whether this is valid because these motifs are embedded in complex larger networks. Here, we explore the conditions for modularity and the bounds of validity of motif analysis in the context of a feedforward motif in the S.cerevisiae network comprising G1/S cell cycle and pheromone pathways. Using modeling and single cell analysis, we find that the feedforward motif accurately predicts the dynamics of the cell cycle inhibitor Far1 because it is insulated from the effects of gradually increasing cell cycle inputs by a positive feedback-driven switch. Before the cell cycle switch, the cell cycle signal has no effect on Far1, so feedforward motif predicts the network behavior. Conversely, after the switch, the feedforward motif is dismantled and has no effect on cell cycle dynamics. When this insulation is broken, the network is no longer modular and the feedforward motif no longer predictive. Thus, switch-like elements can digitize analog signals to modularize complex networks so that smaller sub-networks function in effective isolation and can be analyzed using motif analysis. This work demonstrates how, despite the interconnectivity of networks, motifs can be insulated by switches that produce well-defined cellular states.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Atay, Oguzhan |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Fisher, Daniel |
| Primary advisor | Skotheim, Jan, 1977- |
| Thesis advisor | Fisher, Daniel |
| Thesis advisor | Skotheim, Jan, 1977- |
| Thesis advisor | Feldman, Marcus W |
| Advisor | Feldman, Marcus W |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Oguzhan Atay. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Oguzhan Atay
- License
- This work is licensed under a Creative Commons Attribution Non Commercial Share Alike 3.0 Unported license (CC BY-NC-SA).
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