N OISE P ROPAGATION IN G ENE N ETWORKS Juan M. Pedraza and Alexander van Oudenaarden 1 VC Lab, Dept. of Computer Science, NTHU, Taiwan.

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Presentation transcript:

N OISE P ROPAGATION IN G ENE N ETWORKS Juan M. Pedraza and Alexander van Oudenaarden 1 VC Lab, Dept. of Computer Science, NTHU, Taiwan

N OISE Fluctuations in concentrations 2 VC Lab, Dept. of Computer Science, NTHU, Taiwan Cyan fluorescent protein

S CHEMATIC DESIGN 3 VC Lab, Dept. of Computer Science, NTHU, Taiwan Promoters Fluorescent proteins Cascade Upstream gene Downstream gene

Q UANTIFY Correlation F: fluorescence levels i, j: indices refer to the gene number Self-correlations(variation) Cross-correlations,, 4 VC Lab, Dept. of Computer Science, NTHU, Taiwan

Different manner 5 VC Lab, Dept. of Computer Science, NTHU, Taiwan

S OURCES OF NOISE Intrinsic noise Transmitted intrinsic noise from upstream genes Global noise 6 VC Lab, Dept. of Computer Science, NTHU, Taiwan

I NTRINSIC NOISE Low copy numbers of mRNAs 7 VC Lab, Dept. of Computer Science, NTHU, Taiwan

T RANSMITTED 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 8 VC Lab, Dept. of Computer Science, NTHU, Taiwan

T RANSMITTED INTRINSIC NOISE Susceptibility Logarithmic gain (average expression of j changes when i is varied) 9 VC Lab, Dept. of Computer Science, NTHU, Taiwan

T RANSMITTED INTRINSIC NOISE Susceptibility(Cont.) Example 10 VC Lab, Dept. of Computer Science, NTHU, Taiwan

G LOBAL 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) 11 VC Lab, Dept. of Computer Science, NTHU, Taiwan

N ONINTERACTING GENES dominated by the global noise which is transmitted form gene 1 to gene 2 12 VC Lab, Dept. of Computer Science, NTHU, Taiwan

R ESULT Adding ATC 13 VC Lab, Dept. of Computer Science, NTHU, Taiwan

R ESULT 14 VC Lab, Dept. of Computer Science, NTHU, Taiwan

D ISCUSSION Noise-tolerant synthetic circuits in silico v.s. in vivo 15 VC Lab, Dept. of Computer Science, NTHU, Taiwan

R EFERENCE Tom Ellis, Xiao Wang & James J Collins, Diversity-based, model-guided construction of synthetic gene networks with predicted functions, Nature Biotechnology 27, (2009) 16 VC Lab, Dept. of Computer Science, NTHU, Taiwan