Software systems for Imperial College DNA Foundry (LIMS/automation/interfaces)

Synthetic biology has the tremendous potential for enabling the design and implementation of sophisticated biochemical mechanisms for sensing, computing, control, production, and activation. This approach is anticipated to lead to many breakthrough applications in biotherapeutics, bioremediation, biomaterials, and in vivo-sensing and activation and self-assembly. The hardware available to exploit synthetic biology has evolved to deliver the many protocols for synthesizing DNA and verifying its assembly. Advances in liquid handling, automation, miniaturization, microfluidics and spectroscopy have collectively combined to make possible the rapid construction of synthetic genes, engineered pathways and synthetic genomes. The initial capital funding of this technology at the Centres of DNA Synthesis (The Foundries) has made possible the development of automated workstations organized to synthesize DNA components and assemblies designed to meet defined biofunctional performance parameters. As a direct consequence of the automation of DNA synthesis and assembly there has been a massive increase in throughput, size and complexity of experimental space covered. The research challenge now faced is the lack of an integrated suite of software tools to support DNA synthesis at the Foundry scale. This is part logistical, in the management of the process and data, and part statistical in the interpretation and modeling of the massive amounts of data generated by the Foundry. Similar to the automation of DNA sequencing, automation of synthetic biology in the Foundry will result in the generation and processing of huge amounts of data.
The aims of this proposal:

- Maximize the efficiencies of the Foundry by developing an open source operating system to support an integrated engineering design workflow allowing seamless inter-tool communication for hardware and software.
- Develop a 'Knowledge Centre' capable of providing storage, processing, analysis and predictive modeling of the data coming from DNA design, sequencing, characterization and process metrics generated by the Foundry.
- Build the computational infrastructure to comply with the International Gene Synthesis Consortium (IGSC) to prevent the misuse of synthetic genes. Sequences of DNA synthesized will be screened and users vetted to ensure vigilance and biosecurity of the Foundry.

The operating system will establish a platform to support a suite of synthetic biology software tools, allowing the seamless integration of hardware, management and analysis of the data generated by the Foundry.
The operating system will have two main components:

A suite of interchangeable technologies and software tools serving the needs of the Foundry. These will range from CAD/CAM tools to design the various DNA components, device control linking hardware and software, automated execution of experimental and process workflows, and sample and inventory tracking.

A data management system 'Knowledge Centre' for the storage, processing, analysis, and predictive modeling of data generated by the Foundry. The data, which comes from a range of diverse sources such as DNA design, sequencing, functional data from the characterization process and the Laboratory Information Management System (LIMS), will be an analyzed to uncover meaningful patterns in the high-throughput data generated by the Foundry. The data will be explored using comprehensive set of traditional and advanced statistical algorithms. In the rapidly advancing field of synthetic biology, the ability to conduct sophisticated analyses on large volumes of data and visualize the significance adds a vital new dimension.

The British Government clearly recognises the importance of synthetic biology in relation to the UK's economic development. The field has been identified as one of the Government's "8 Great Technologies" and this has been endorsed by The World Economic Forum. Synthetic biology is a classic example of a knowledge-based industrial area, which is leveraging the UKs science and engineering base. Effective industrial translation is, therefore, a key element in the development of new processes and industries. Standardisation is central to industrial translation and industrial processes. Consequently, an important component of this process in synthetic biology is the handling, assembly and verification of DNA components of various lengths - and in the context of various cellular hosts. The proposal, building on the funding already in place for the foundry, is based on the development of an operating system of integrated software tools to complete the design, build, test, report and learn cycle paradigm. The impact of this will be to create a foundry capable of providing automated end-to-end design, construction and validation of large gene constructs for academia and industry. The Foundries ability to effectively translate academic research into industrial products and services is critically dependent on the availability and integration of software to manage and engineer the design process. Modern process development and production is heavily dependent software design tools to perform Design of Experiments (DoE), Quality by Design (QbD) and Six-sigma, without access to these tools it will be increasing difficult to interact with any commercial partners. Investment in the development and integration of a suite of software tools for DNA synthesis aligns with the Foundry's mission to provide a standardized framework for DNA synthesis, gene and genome assembly and assembly verification. It is envisioned that an integrated suite of software tools for DNA synthesis developed, and the open source operating structure, will interface with other software and hardware. The creation of a standardized operating system for DNA synthesis and assembly has the potential to encourage commercial software developers and hardware companies to develop tools which will interface with the operating system. The integration of industry-standard hardware and open source software, when fully implemented and tested it will be possible to replicate the operating system at multiple foundries around the UK.
In summary, we believe the operating system we are proposing, is strategically important for synthetic biology research, its translation and the development of UK industry in the field. Our strategy is to create and implement an operating system to serve the Foundry, which will enable the UK to have significant capability and expertise in DNA synthesis, assembly and verification now and in the longer term.