In the pursuit of cost-effective genomics testing, researchers and clinicians face a challenging trade-off. While whole genome sequencing (WGS) provides comprehensive genetic insights, its high cost remains a significant barrier, particularly for large-scale studies. Many have turned to whole exome sequencing (WES) as a more economical alternative, but its focus on protein-coding regions alone leaves gaps in our understanding. To bridge this divide, teams often combine multiple approaches – running WES alongside microarrays with imputation. However, this patchwork solution introduces its own challenges: potential data bias, increased sample requirements, and the complex task of integrating results from different platforms.
To address these challenges, the team at Broad Clinical Labs (BCL) has developed an innovative new assay – Clinical Blended Genome-Exome (cBGE) Sequencing. This streamlined, single-sample approach combines low-coverage, PCR-free WGS with high-depth WES in a single, cost-effective assay, ideal for large-scale studies, clinical trials, and affordable patient genetic testing. This assay offers concurrent estimation of both polygenic and monogenic disease risk, enabling a more precise risk profile to inform risk models, enrich clinical outcome assessment, and provide maximum information to clinicians and patients.
The cBGE Assay: Sample to Result in just 28 days
The qualitative cBGE assay begins with genomic DNA extraction from a blood or saliva sample, followed by the generation of a PCR-free whole genome library. Next, an aliquot of the library undergoes PCR amplification and exome selection. The genome and exome libraries are then recombined for sequencing on the powerful Illumina® NovaSeq X Plus platform.
The result is a single CRAM file containing 2–4X WGS and 85–100X WES data (Figure 1). Alignment and variant calling are performed using the Illumina® DRAGEN platform, with clinical reporting available upon request.
Figure 1. The Clinical Blended Genome-Exome Assay yields low-coverage WGS and high-coverage WES data from a single sample. Both data types are delivered in a single CRAM file.
All testing for the cBGE assay is conducted in BCL’s CLIA-licensed and CAP-accredited laboratory by an expert team with decades of experience, ensuring the highest standards of quality and reliability. BCL’s streamlined workflow and scalable sample processing of up to hundreds of thousands of samples per year, enable us to provide this service at a low cost, starting at just $120 per sample, with no sample minimums.
Creating Opportunities to Improve Patient Care
The applications of this innovative cBGE assay are wide-ranging. It provides a cost-effective alternative to microarrays for genotyping in GWAS studies, enabling germline gene-disease discovery. The low-pass WGS component is well-suited for common variant detection in population genetic diversity and community health studies, while the deep WES data enables sensitive detection of rare genetic variants (SNVs, small indels, and CNVs). Together, this combined approach supports both monogenic and polygenic risk analysis.
Our cBGE assay is already being used to power studies like ProGRESS, a prostate cancer genetic risk screening trial, in partnership with Genomes2Veterans. In addition, we are utilizing the cBGE assay to provide no-cost genetic testing for patients in Alabama as part of the Catalyst program in collaboration with Southern Research and MyOme, with a goal of bringing genetics-driven clinical risk assessments to underserved communities.
By combining the breadth of WGS with the depth of WES in a single, cost-effective assay, our aim is to unlock comprehensive genomic insights for every patient and empower researchers to conduct large-scale studies to advance personalized medicine.
Learn more about our Clinical Blended Genome-Exome Assay and how it can power your clinical applications on our service page.
