The SHOP2 planning system received one of the awards for distinguished performance in the 2002 International Planning Competition. This paper describes the features of SHOP2 which enabled it to excel in the competition, especially those aspects of SHOP2 that deal with temporal and metric planning domains.

A long-standing goal of synthetic biology is to rapidly engineer new regulatory circuits from simpler devices. As circuit complexity grows, it becomes increasingly important to guide design with quantitative models, but previous efforts have been hindered by lack of predictive accuracy. To address this, we developed Empirical Quantitative Incremental Prediction (EQuIP), a new method for accurate prediction of genetic regulatory network behavior from detailed characterizations of their components. In EQuIP, precisely calibrated time-series and dosage-response assays are used to construct hybrid phenotypic/mechanistic models of regulatory processes. This hybrid method ensures that model parameters match observable phenomena, using phenotypic formulation where current hypotheses about biological mechanisms do not agree closely with experimental observations. We demonstrate EQuIP's precision at predicting distributions of cell behaviors for six transcriptional cascades and three feed-forward circuits in mammalian cells. Our cascade predictions have only 1.6-fold mean error over a 261-fold mean range of fluorescence variation, owing primarily to calibrated measurements and piecewise-linear models. Predictions for three feed-forward circuits had a 2.0-fold mean error on a 333-fold mean range, further demonstrating that EQuIP can scale to more complex systems. Such accurate predictions will foster reliable forward engineering of complex biological circuits from libraries of standardized devices.

This Supporting Information document contains method detail for the paper "An End-to-End Workflow for Engineering of Biological Networks from High-Level Specifications." In particular, it details:• The computational tools used and how they were executed.• Protocols used for DNA preparation and assembly• Protocols used for cell culture and FACS• Details of optical microscopy• Methods for analysis of FACS data Computational ToolsThe compilation process used a standard Release 6 installation of the Proto p2b stand-alone compiler, 1 configured with neocompiler option. The Proto BioCompiler 2 was coded in C++ as a Proto plug-in. Both were executed on a standard MacBook laptop, with negligible execution time ( 1 second). The compilation process was executed using input configurations stored in Proto code files and invoked for each platform via command-line arguments. Intermediate models were recorded by means of standard Proto logging facilities. The final Proto BioCompiler AGRN output was encoded in a custom XML format based on SBOL 1.0. 3 MatchMaker was coded in Java as a stand-alone application, and also wrapped to produce a Clotho 4 application, for Clotho 2.0 ("tasbe"). The Clotho application version has interfaces to initialize feature, signal and part databases from Clotho databases. The algorithms and mathematical formulation of the feature matching, signal matching and part matching steps explained in detail in a stand-alone paper which is currently under review for publication. 5 MatchMaker was executed on a standard MacBook laptop, with negligible running time (under 1 second).

Raising the level of abstraction for synthetic biology design requires solving several challenging problems, including mapping abstract designs to DNA sequences. In this paper we present the first formalism and algorithms to address this problem. The key steps of this transformation are feature matching, signal matching, and part matching. Feature matching ensures that the mapping satisfies the regulatory relationships in the abstract design. Signal matching ensures that the expression levels of functional units are compatible. Finally, part matching finds a DNA part sequence that can implement the design. Our software tool MatchMaker implements these three steps.

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