Noise Propagation in Gene Networks

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Presentation transcript:

Noise Propagation in Gene Networks VC Lab, Dept. of Computer Science, NTHU, Taiwan Juan M. Pedraza and Alexander van Oudenaarden

Cyan fluorescent protein Noise Fluctuations in concentrations VC Lab, Dept. of Computer Science, NTHU, Taiwan Cyan fluorescent protein

Schematic design Upstream gene Downstream gene Cascade Promoters Fluorescent proteins VC Lab, Dept. of Computer Science, NTHU, Taiwan

Quantify Correlation Self-correlations(variation) Cross-correlations F: fluorescence levels i, j: indices refer to the gene number Self-correlations(variation) Cross-correlations , , VC Lab, Dept. of Computer Science, NTHU, Taiwan

Different manner VC Lab, Dept. of Computer Science, NTHU, Taiwan

Sources of noise Intrinsic noise Transmitted intrinsic noise from upstream genes Global noise VC Lab, Dept. of Computer Science, NTHU, Taiwan

Intrinsic noise Low copy numbers of mRNAs VC Lab, Dept. of Computer Science, NTHU, Taiwan

Transmitted intrinsic noise Three factors Intrinsic noise for upstream gene The effect of temporal averaging(depends on the lifetimes of the proteins) Susceptibility of the downstream gene to the upstream one VC Lab, Dept. of Computer Science, NTHU, Taiwan

Transmitted intrinsic noise Susceptibility Logarithmic gain (average expression of j changes when i is varied) VC Lab, Dept. of Computer Science, NTHU, Taiwan

Transmitted intrinsic noise Susceptibility(Cont.) Example VC Lab, Dept. of Computer Science, NTHU, Taiwan

Global noise Cellular components change the reaction rate Transmitted global fluctuation does not simply add to the direct global noise (because they are from same source) VC Lab, Dept. of Computer Science, NTHU, Taiwan

Noninteracting genes dominated by the global noise which is transmitted form gene 1 to gene 2 VC Lab, Dept. of Computer Science, NTHU, Taiwan

Result Adding ATC VC Lab, Dept. of Computer Science, NTHU, Taiwan

Result VC Lab, Dept. of Computer Science, NTHU, Taiwan

Discussion Noise-tolerant synthetic circuits in silico v.s. in vivo VC Lab, Dept. of Computer Science, NTHU, Taiwan

Reference Tom Ellis, Xiao Wang & James J Collins, Diversity-based, model-guided construction of synthetic gene networks with predicted functions, Nature Biotechnology 27, 465-471(2009) VC Lab, Dept. of Computer Science, NTHU, Taiwan