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AGBT19 Poster - Rapid clinical whole genome sequencing: a scalable <3 day process

Author List:(presenter in bold, rest alpha): Sam DeLuca, Tom Howd, Fontina Kelley, Mike DaSilva, Tim Desmet, Katie Larkin, Tamara Mason, Steve Ferreira, Jim Meldrim, Maegan Harden, Alyssa Macbeth, Betty Woolf, Kathleen Tibbetts, Eric Banks, Laura Gauthier, Sam Friedman, Lee Lichtenstein, Wendy Brodeur, Matt Lebo, Sheila Dodge, Heidi Rehm, Stacey Gabriel, Niall Lennon.

Broad Institute of MIT and Harvard.


As precision medicine moves from the realm of clinical utility studies towards standard of care, there is a pressing need to decrease turnaround times for WGS data generation as part of an end-to-end clinical workflow. In the last year, we have validated and launched a clinical WGS product with a deliverable of 95% of bases at ≥ 20X coverage within the industry standard of 28 calendar days. Here, we present how we have since built a scalable workflow around this clinical grade, gold standard PCR-Free genome process that allows for sample intake to return of data in 5 days.  


In order for us to accomplish our goal of a 5 day clinical grade genome, we needed to take advantage of a streamlined, dynamic workflow which incorporates our internally developed LIMS and state of the art automation technology. Within 48 hours of sample intake, we are capable of registering blood tubes into our LIMS system, performing an automated extraction followed by a series of internal QC assays, generating PCR-Free libraries, and having them on sequencing instruments. We have implemented several principles from lean manufacturing and dynamic work design in order to minimize waste and eliminate unnecessary touch points or delays in the workflow.


For this rapid WGS application, we have chosen to utilize an S2 flow cell on the NovaSeq 6000, which provides complete sequencing data in only 25 hours. Data transfer from the sequencing platform to an analysis pipeline is automatically started upon run completion. Significant improvements to our data analysis pipeline have allowed for us to integrate GATK calling with advanced single sample filtering to provide vcf files that include functional annotations within 48 hours of sequencing being completed.

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