This presentation from Broad Clinical Labs outlines their focus on translating groundbreaking genomics technology into clinical practice, particularly leveraging the Roche sequencing platform. The speaker details a collaboration aimed at optimizing rapid whole genome sequencing (rWGS) for critically ill neonatal intensive care unit (NICU) patients, where timely diagnosis significantly impacts patient management. Key achievements include dramatically reducing sequencing turnaround times: initial three-sample runs in 12 hours 10 minutes, single-sample sequencing optimized to 4 hours 25 minutes, and trio sequencing (three samples) achieved in 7 hours 8 minutes. The platform successfully detected causative variants across various types (SNVs, indels, CNVs, repeat expansions) in numerous patient cell lines and previously diagnosed clinical samples. Furthermore, the generated data seamlessly integrated with clinical tertiary analysis software (Fabric Genomics), demonstrating its potential for efficient variant prioritization. Future efforts, under a new collaboration agreement with Roche, will focus on bioinformatics optimization, automation, broader tertiary platform integration, end-to-end workflow validation, and the ultimate goal of implementing sub-one-day rWGS for routine patient care.
Exploring Rapid Whole Genome Sequencing for Clinical Application
0:00 Broad Clinical Labs' Mission: Broad Clinical Labs, a large US-based sequencing center, focuses on translating cutting-edge genomics research and large-scale data into practical clinical applications, often serving as a proving ground for new technologies.
1:28 Roche Sequencer Capabilities: A collaboration with Roche began over a year ago to evaluate their nanopore and expandimer sequencer, which demonstrated impressive claims of high accuracy, speed, and scalability due to the ability to run many smaller batches.
3:18 Key Application: Rapid NICU Genome: The technology is ideally suited for rapid whole genome sequencing in Neonatal Intensive Care Units (NICU), where early diagnosis of monogenic conditions (found in ~60% of patients) can significantly reduce patient and healthcare system burden, even if therapeutic interventions aren't always available.
5:22 Initial Speed Achievements: After receiving the system in January and quickly setting it up, initial three-sample runs achieved a turnaround time of 12 hours and 10 minutes. This was further optimized to a remarkable 4 hours and 25 minutes for a single sample.
6:29 Trio Sequencing Optimization: Recognizing the clinical importance of trio analysis (mom, dad, proband), the team achieved sequencing three whole genomes from DNA to variants in 8 hours and 2 minutes, subsequently reducing this to a consistent 7 hours and 8 minutes with greater than 30x coverage.
7:06 Clinical Variant Detection: The platform successfully detected causative variants (including small variants, large copy number events, and repeat expansions) in various patient cell lines and previously diagnosed clinical samples, demonstrating its diagnostic utility.
9:50 Integration with Tertiary Analysis: Data from the Roche sequencer successfully integrated with Fabric Genomics, a tertiary analysis platform used clinically by Broad, allowing for effective prioritization of causative variants, performing similarly to other short-read technologies.
14:02 Future Goals: A collaboration agreement with Roche aims to further optimize bioinformatics for complex variants, implement automation, test with diverse tertiary analysis platforms, validate an end-to-end workflow, and ultimately achieve sub-one-day, one-shift rapid genome sequencing for routine patient care.