The key deliverables of the MLPCN are public data of high quality, published to PubChem, and supporting chemical probe development.  This mission requires two essential components, an Operational Environment for data management and QA, and a Knowledge Environment facilitating efficient chemical probe optimization. The Scripps Center has built these on a comprehensive production scale and will make key tools available broadly to maximize the impact of the MLPCN effort.

Our operational infrastructure (pictured below) includes chemical structure registration with application and user business rules, flexible sample and plate logistics, and assay protocol and assay data management systems. These systems are integrated with our laboratory automation infrastructure to efficiently process HTS screening campaigns.  Key integration components are Plato and Nightwatch.  These allow querying and synchronizing plates on the Kalypsys system with the Plate Manager database. Hit picking functionality takes hit lists in various formats and generates optimized TECAN input files and creates the corresponding plates in the Plate Manager database. Plate transformation functionality includes creating of ‘cherry picking’ plates and ‘dose response’ plates.

Figure 1.  Overview of informatics environment (Click image to expand). A) MLSMR external compound repository provides chemical structure, plate, and well shipment data, which are pre-processed via Pipeline Pilot (PP) protocols B) and registered into the MDL-based central compound registration system C). After association with corporate compound and batch IDs, plate information is registered into the MDL-based Plate logistics system D), which is integrated via an in-house developed web-based system (Plato) E) with our uHTS robotics system (Kalypsys) F). Screening progress is monitored via in-house developed software (NightWatch) G) and loaded into MDL Assay Explorer H). Assay results are processed and published via automated PP protocols I) into Pubchem J). Released screening data is picked up via PP integration K) and aggregated by metrics into the central data warehouse (Oasis) L). Oasis retrieves structures via the MDL chemical registration database C). Oasis can be queried via ISIS RAF or our in-house ChemInfo portal (not shown) or PP Webport M) to produce SAR reports M). As an example of integration of discovery systems, structures from the MDL database are loaded into LeadScope O) via a PP structure loader N). Pubchem MLSMR structures J) are kept updated in LeadScope using the structure loader. Project-specific data is loaded via PP processes N) from Oasis L) into Leadscope O). After data analysis in Leadscope results are reported using the PP reporting collection P) into interactive heat map and SAR reports Q).