The current market state of Whole Exome Sequencing
Jun 28, 2018

How to navigate the complex world of Whole Exome Sequencing

For patients, family members, and healthcare professionals, uncertainty surrounding a genetic diagnosis can be quite painful. Utilization of high quality and comprehensive next-generation sequencing (NGS) technologies can significantly improve the diagnostic yield in these patients and end the “diagnostic odyssey” before it even begins.

The benefits of WES are manifold

  • Functions as an excellent tool for complex cases where selecting a targeted test is difficult
  • Allows for identification of atypical gene-phenotype associations
  • Simplifies the panel selection process since all genes are covered
  • There is no need to update target regions when new disease genes are identified

Unfortunately, NGS technologies can harbor significant challenges that affect a lab’s ability to maximize diagnostic yield and potentially risk a patient’s successful disease management.

In addition, the significant quality and performance variability between well-known laboratories, lack of transparency in demonstrating test performance through comprehensive and well-executed analytic validation studies, and the deficiency of training and education within the medical community about these challenges is quite alarming.

We are faced with the question of how to address these challenges

The medical community must be equipped with the necessary knowledge to critically evaluate the multitude of testing options available to them. The first characteristic clinicians need to be aware of is the performance and quality of the WES platform they are evaluating. This is accomplished through an in-depth look into the lab’s analytic validation and quality standards. Unfortunately, many laboratories hide their analytic validations from the public which presents a real problem for clinicians.

Clinicians need to determine if all the genes relevant to their patient are covered by the WES platform. High and uniform sequencing coverage is critical for robust variant detection. On traditional platforms, we frequently see low sequencing coverage especially on hard-to-sequence regions. Through a comprehensive, tailored and optimized WES analysis, we can significantly improve the overall coverage, detection of copy number variants, larger indels, and clinically significant non-coding variants, and coverage for hard-to-sequence genomic regions. These improvements lead to an improved diagnostic yield.

Key Objectives

  • Summarize challenges of today’s NGS technologies, outlined strategies used to identify high-quality NGS tests
  • Provide interlaboratory WES performance comparisons
  • Outline Blueprint Genetics’ high-performance clinical grade WES platform which offers “panel” quality on a WES scale.

PRESENTATION: How to Navigate the Complex World of Whole Exome Sequencing

“Utilization of Whole Exome Sequencing for Genetic Diagnostics of Rare Pediatric Diseases” was presented in the 2018 Canadian Pediatric Society Annual Conference. You can access it here.


Tero-Pekka Alastalo

Tero-Pekka is the Executive Director of Medical, and also a co-founder at Blueprint Genetics. He is based in San Francisco and holds various responsibilities in the North American operations of the company. Tero-Pekka has an MD-PhD degree and is specialized in pediatrics and pediatric cardiology. He has a PhD in molecular and cellular biology as well. During his 3-year postdoctoral training at Stanford University School of Medicine, he focused on the molecular genetic mechanisms of cardiovascular disease.

Last modified: October 30, 2020