[Slides] Formal languages to map Genotype to Phenotype in Natural Genomes.
Adam, L. Formal languages to map Genotype to Phenotype in Natural Genomes. GBCB seminar, 2012.
Speaker: Laura Adam, GBCB Doctoral Candidate Advisor: Jean Peccoud, VBI
Title: Formal languages to map Genotype to Phenotype in Natural Genomes
Abstract: To formalize Genotype-to-Phenotype mapping and confer predictive powers, missing in current approaches, information from genomic databases and mathematical models can be encompassed in a logical and structured fashion, by the means of formal languages. In other words, syntax and meaning, that is genome and phenotype, will be integrated into a computational system to explore the phenotype of novel mutants. As a result, a bridge between the information obtained by systems biologists and the observations of molecular processes can be built, facilitating communication between different communities. We use DNA sequence compilation, based on attribute grammars, in the synthetic biology design process (Cai, Lux, Adam, & Peccoud, 2009), which appears to be ideal to compute the nonlinear relationships of the G2P mapping problem. GenoCAD, a rule-based biodesign tool, implements those concepts to support genetic design from assembling standardized parts to simulation and illustrate it with examples of genetic toggle switches (Gardner, Cantor, & Collins, 2000) and oscillators (Elowitz & Leibler, 2000). Additionally, GenoCAD offers a graphical user interface for the development of grammars and thus, supports the generation of the corresponding semantic DNA compilers, making genetic design tools user-friendly to the majority and still adaptable to specific projects. Additionally, in order to show that this approach is scalable to natural genomes and system biology, we are developing an attribute grammar to design the yeast genome and its mutants; the corresponding cell cycle mathematical model will be derived accordingly.
References: Cai, Y., Lux, M. W., Adam, L., & Peccoud, J. (2009). Modeling structure-function relationships in synthetic DNA sequences using attribute grammars. PLoS computational biology, 5(10), e1000529. doi:10.1371/journal.pcbi.1000529
Elowitz, M. B., & Leibler, S. (2000). A synthetic oscillatory network of transcriptional regulators. Nature, 403(6767), 335–8. doi:10.1038/35002125 Gardner, T. S., Cantor, C. R., & Collins, J. J. (2000). Construction of a genetic toggle switch in Escherichia coli. Nature, 403(6767), 339–42. doi:10.1038/35002131