In-house software and processes to support High Content Screening of Primary Neurons
Recorded On: 02/07/2018
The integration of High Content Screening (HCS) devices onto High Throughput Screening (HTS) platforms to support neuroscience research presents unique challenges for drug discovery teams. In particular, the informatics aspect of HCS applied to neuroscience is an area where advances in software automation can result in substantial throughput and efficiency gains for researchers. In addition to the data processing and storage requirements of HCS above traditional HTS readers, neuroscience assays present a number of unique challenges for the HTS environment. These challenges include ensuring data integrity from acquisition through analysis & QC, porting data between multiple distinct HCS platforms and providing end-user analytic tools for ongoing intermediate assay results.
This presentation will focus on the development and implementation of novel in-house software utilities used at Scripps Florida to support the Synaptogenesis neuroscience drug discovery project. This project utilizes multiple HCS platforms, has an ongoing non-traditional HTS timeline and requires on-demand access to the full HCS data stream, from raw source images to final endpoint results. The biology of the Synaptogenesis project is currently amenable to 384 well format while the Scripps Florida uHTS platform is optimized for 1536 well screening. Supporting a HTS campaign where the compound collection resides in a different plate density than the assay plate required the development of custom robotic and informatics procedures. The Synaptogenesis endpoint calculation requires measurements at DIV 12 and DIV 14 where each assay plate is represented by 3,072 images (384 wells at 4 images per well for each of two separate reads) which must be associated with relevant metadata (plate barcode, well row, well column and well quadrant) for downstream tracking. Previous neuroscience assays in this format were not amenable to robotics screening and were limited in throughput. To date, we have successfully screened a large portion (greater than 40,000 compounds) of the Scripps Drug Discovery library, in quadruplicate, iteratively over a 9 month period.
To meet these challenges, custom software tools have been developed which enables scientists to manage what would otherwise be an overwhelming amount of data. These tools include a web based portal that allows end users to easily review HCS neuroscience data as it comes off the HTS platform and to quickly drill down on endpoint data back to the images acquired by the reader. The advantages of developing in-house informatics over commercial products and the impact of these tools on the ongoing neuroscience research at Scripps Florida is presented.
Pierre established the Compound Management team within the Lead Identification/HTS group at Scripps Florida when the lab was established in 2005. The Compound Management team is responsible for supporting both industrial and academic drug discovery efforts with a proprietary >600,000 sample library and the NIH's >300,000 sample MLPCN collection. Aside from typical Compound Management duties, Pierre has developed, assembled and integrated novel automated hardware and software for the purpose of drug discovery.