Oncotarget

Research Papers:

Analytic validation of NeXT Dx™, a comprehensive genomic profiling assay

Juan-Sebastian Saldivar, Jason Harris, Erin Ayash, Manqing Hong, Prateek Tandon, Saloni Sinha, Patricia Miranda Hebron, Erin E. Houghton, Kaleigh Thorne, Laurie J. Goodman, Conan Li, Twinkal R. Marfatia, Joshua Anderson, Massimo Morra, John Lyle, Gabor Bartha and Richard Chen _

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Oncotarget. 2023; 14:789-806. https://doi.org/10.18632/oncotarget.28490

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Abstract

Juan-Sebastian Saldivar1,*, Jason Harris1,*, Erin Ayash1, Manqing Hong1, Prateek Tandon1, Saloni Sinha1, Patricia Miranda Hebron1, Erin E. Houghton1, Kaleigh Thorne1, Laurie J. Goodman1, Conan Li1, Twinkal R. Marfatia1, Joshua Anderson1, Massimo Morra1, John Lyle1, Gabor Bartha1 and Richard Chen1

1 Personalis, Inc., Fremont, CA 94555, USA

2 These authors contributed equally to this work

Correspondence to:

Richard Chen, email: [email protected]

Keywords: comprehensive genomic profiling; whole exome sequencing; whole transcriptome sequencing; tumor-normal; precision medicine

Received: May 31, 2023     Accepted: August 19, 2023     Published: August 30, 2023

Copyright: © 2023 Saldivar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

We describe the analytic validation of NeXT Dx, a comprehensive genomic profiling assay to aid therapy and clinical trial selection for patients diagnosed with solid tumor cancers. Proprietary methods were utilized to perform whole exome and whole transcriptome sequencing for detection of single nucleotide variants (SNVs), insertions/deletions (indels), copy number alterations (CNAs), and gene fusions, and determination of tumor mutation burden and microsatellite instability. Variant calling is enhanced by sequencing a patient-specific normal sample from, for example, a blood specimen. This provides highly accurate somatic variant calls as well as the incidental reporting of pathogenic and likely pathogenic germline alterations. Fusion detection via RNA sequencing provides more extensive and accurate fusion calling compared to DNA-based tests. NeXT Dx features the proprietary Accuracy and Content Enhanced technology, developed to optimize sequencing and provide more uniform coverage across the exome. The exome was validated at a median sequencing depth of >500x. While variants from 401 cancer-associated genes are currently reported from the assay, the exome/transcriptome assay is broadly validated to enable reporting of additional variants as they become clinically relevant. NeXT Dx demonstrated analytic sensitivities as follows: SNVs (99.4%), indels (98.2%), CNAs (98.0%), and fusions (95.8%). The overall analytic specificity was >99.0%.


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PII: 28490