Synthetic biology is a complex discipline that involves creating detailed, purpose-built designs from genetic parts. This process is often phrased as a Design-Build-Test-Learn loop, where iterative design improvements can be made, implemented, measured, and analyzed. Automation can potentially improve both the end-to-end duration of the process and the utility of data produced by the process. One of the most important considerations for the development of effective automation and quality data is a rigorous description of implicit knowledge encoded as a formal knowledge representation. The development of knowledge representation for the process poses a number of challenges, including developing effective human−machine interfaces, protecting against and repairing user error, providing flexibility for terminological mismatches, and supporting extensibility to new experimental types. We address these challenges with the DARPA SD2 Round Trip software architecture. The Round Trip is an open architecture that automates many of the key steps in the Test and Learn phases of a Design-Build-Test-Learn loop for highthroughput laboratory science. The primary contribution of the Round Trip is to assist with and otherwise automate metadata creation, curation, standardization, and linkage with experimental data. The Round Trip's focus on metadata supports fast, automated, and replicable analysis of experiments as well as experimental situational awareness and experimental interpretability. We highlight the major software components and data representations that enable the Round Trip to speed up the design and analysis of experiments by 2 orders of magnitude over prior ad hoc methods. These contributions support a number of experimental protocols and experimental types, demonstrating the Round Trip's breadth and extensibility. We describe both an illustrative use case using the Round Trip for an on-the-loop experimental campaign and overall contributions to reducing experimental analysis time and increasing data product volume in the SD2 program.

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Computational tools addressing various components of design-build-test-learn loops (DBTL) for the construction of synthetic genetic networks exist, but do not generally cover the entire DBTL loop. This manuscript introduces an end-to-end sequence of tools that together form a DBTL loop called DART (Design Assemble Round Trip). DART provides rational selection and refinement of genetic parts to construct and test a circuit. Computational support for experimental process, metadata management, standardized data collection, and reproducible data analysis is provided via the previously published Round Trip (RT) test-learn loop. The primary focus of this work is on the Design Assemble (DA) part of the tool chain, which improves on previous techniques by screening up to thousands of network topologies for robust performance using a novel robustness score derived from dynamical behavior based on circuit topology only. In addition, novel experimental support software is introduced for the assembly of genetic circuits. A complete design-through-analysis sequence is presented using several OR and NOR circuit designs, with and without structural redundancy, that are implemented in budding yeast. The execution of DART tested the predictions of the design tools, specifically with regard to robust and reproducible performance under different experimental conditions. The data analysis depended on a novel application of machine learning techniques to segment bimodal flow cytometry distributions. Evidence is presented that, in some cases, a more complex build may impart more robustness and reproducibility across experimental conditions.

If we wish to embed assessment for accountability within instruction, we need to better understand the relative contribution of different types of learner data to statistical models that predict scores and discrete achievement levels on assessments used for accountability purposes. The present work scales up and extends predictive models of math test scores and achievement levels from existing literature and specifies six categories of models that incorporate information about student prior knowledge, demographics, and performance within the MATHia intelligent tutoring system. Linear regression, ordinal logistic regression, and random forest regression and classification models are learned within each category and generalized over a sample of 23,000+ learners in Grades 6, 7, and 8 over three academic years in Miami-Dade County Public Schools. After briefly exploring hierarchical models of this data, we discuss a variety of technical and practical applications, limitations, and open questions related to this work, especially concerning to the potential use of instructional platforms like MATHia as a replacement for time-consuming standardized tests. Notes for Practice• Advanced educational technologies, including simulations, games, and intelligent tutoring systems, continually assess students in order to provide them with appropriate activities and to determine their mastery of the topics presented.• The assessment embedded in adaptive systems is a type of formative assessment, but we can also use it to make summative conclusions about what a student has learned.• We show that process data collected from students using MATHia, an intelligent tutoring system, over the course of a year can predict high-stakes test scores over and above the ability of a prioryear test to predict these scores.• Models learned on data from a single academic year can be used to predict outcomes for students in other academic years, suggesting that significant predictors of student outcomes remain relatively stable from year to year.• The ability to predict high-stakes exam scores is a necessary (though insufficient) step towards replacing such exams with embedded formative assessments, but even if high-stakes exams remain in place, predictive tools can provide important information about learner readiness for such highstakes exams.