The volume of raw data, processed information and knowledge management brokering anticipated in bioinformatics is set to accelerate over the forthcoming years by several orders of magnitude. Moreover, following the recent US (Patent Office) ruling, there is now the requirement to demonstrate 'a utility' for a gene before it can be patented, and, as a result, the volume of proteomics data promises to be magnitudes greater than that generated from genomics. The software engines and infrastructure frameworks, with which we expect to be confronted, remain limited by the delivery of suitable products. In spite of the cross-industry acceptance of the Laboratory Information Management System (LIMS), it is a generally held view in the bioresearch community that conventional LIMS applications are simply too inflexible to meet requirements of both the bioinformatician and their clients, without considerable customization. If this is true then a gaping hole exists for the processing of laboratory data in biotechnology; vital in generating leads, terminating flawed projects early and making more informed decisions. In data acquisition and analysis, the LIMS has been the tool of choice within the world's pharmaceutical industry since rudimentary - almost exclusively in-house developed - systems made their appearance in the late 1960s. The main driver for the introduction of LIMS was the burden of regulatory compliance. A LIMS offered secure data handling, instrument integration, audit trails, etc. Continual development has facilitated the implementation of LIMS in a wide range of laboratory types, including research & development, production, QA/QC, contract testing and environmental testing. However, the provision of a comprehensive sample inventory and the ability to track microtiter plates and micro-arrays are considered pre-requisites for LIMS in genomics and proteomics applications. LIMS for biotech must enable the identification of patterns in the huge volumes of data and trace back to original source material. The design of Nautilus LIMS benefits from having no enforced concept of 'sample and task' entities, therefore deployment and configuration for genotyping, cloning and metabolomics is accommodated. Through the use of a hierarchy of need concept in Nautilus, the complex inter-relationships of proteomic or genomic samples can be handled with ease. In close collaboration with its client base and benefiting from the experience of instrumentation scientists and engineers at its parent, the Thermo Fisher Scientific, Thermo LabSystems is addressing these requirements with a host of enhancements to its Nautilus LIMS product for the specific needs of the bio-informatician. Not to be overlooked is the program of alliances the company has forged with a select array of specialist vendors of complementary technologies.

Amongst the new enhancements to Nautilus have been advanced data management capabilities for techniques including cDNA library management, SNP scoring, sequencing, genotyping and sequencer integration. However, the highlight in the new bio-Nautilus offering is functionality for plate/array handling. Any laboratory performing molecular biology assays needs to be able to fill plates, re-array from one microtiter plate to another (96 to 384 to 1536 and vice-versa), track and select individual aliquots in any well, and "cherry-pick" aliquots of interest (e.g. aliquots with positive results) onto a new plate. Nautilus functionality handles the filling of microtiter plates (96 wells) to micro-arrays (up to 82944 spots). Plate fill orders and patterns can be defined using a simple graphical user interface, and "daughter" plates, and their eventual results can be traced back through parental generations. The Nautilus Explorer interface allows the easy review of individual plates with child plates and aliquots displayed beneath them in the hierarchy. Plate property sheets detail all information about the plate, including the aliquots that have been loaded on to it. A plate's available positions, their aliquot types and the fill order can be graphically defined using a Plate Template. Plate result entry is one of the major areas of productivity gain when using the latest version of Nautilus and probably one of the most powerful features of the product. Result entry for plate aliquots is automated through direct integration with the instrument in use. Results may be entered based on plate position or aliquot reference. The system features advanced instrument control mapping commands, which deal with plate login and plate result entry.

Workflows in Nautilus

The Workflow feature of Nautilus enables the user to graphically map the actual laboratory workflow and sample life cycle onto the Nautilus, without software coding or the necessity for IT specialists. This process concludes with the automated assignment or creation of all relevant dilutions, aliquots, analyses, results and associated reports. Similarly, any changes to a working practice can be versioned for compliance and regulatory needs.
A plate's lifecycle is determined by the plate workflow used to build the plate. These workflows are used to automate decisions and actions throughout a plate's lifecycle. This permits a full work action and decision tree process to be built and formatted against user project requirements.

3rd-Party System Integration

Nautilus has been designed with the integration of analytical instruments as a principle component of the LIMS architecture. The ability to easily import and export data and analysis files is therefore provided within Nautilus, as standard with no third party products or services required. This is an area of Nautilus currently being exploited by Roslin Institute as part of its European Union-funded ARK-Genomics project, which is developing micro-array technology for farm animal research groups. In Roslin's past experience importing files can be a complex, time-consuming process that required re-coding each time a new format is introduced. Electronic data capture within Nautilus has eased this process and allows the integration of external information, from a wide variety of sources, with the data on specific wells held in Nautilus. By simply providing an example file to the Nautilus Integration Editor and effectively stepping the system through the parsing of that file, a script is generated that can automatically parse files of that format and assign the relevant data into the database. Additionally, Thermo LabSystems has sought to develop relationships with specialist vendors of complementary technologies to ensure Nautilus fully supports users in the field of bioinformatics. For example, the company has a product integration partnership with Spotfire Inc, a leading supplier of Web-enabled decision analytics software.
This initiative is designed to further accelerate biotechnology and pharmaceutical product development and delivery. Thermo LabSystems has worked with Sagitus Solutions to integrate Nautilus with its leading Max-D solution for micro-array analysis. Additionally, Nautilus incorporates specifically built functionality for connectivity to peptide sequencing software, ADME/DMPK applications as well as industry standard MS and chromatography data system environments. Finally, Thermo LabSystems has also recently announced a collaborative agreement with NextGen Sciences Ltd, the UK-based technology development company specializing in providing automated solutions for the genomics, transcriptomics and proteomics markets. The two companies will implement Nautilus at NextGen to enable full management of the production of protein biochips from individual cultures, purified recombinant proteins and other biomaterials, through the protein array process to the final assay result.

Summary

The biotechnology environment poses a number of specific challenges to the LIMS developer. Thermo LabSystems claims that the latest version of its Nautilus product, along with our partners' complementary technologies, brings to the market new levels of user empowerment, project traceability, data and instrument integration to offer organizations full supply chain/chain of custody in their discovery operations.
* This article originally appeared in Laboratory/Biomedical News September 2001