Center for Genomic Interpretation Podcast Highlights How ‘In Silico Proficiency’ Testing Assesses Genetic Testing Accuracy

Jan 25, 2022 | News, Press Release

Center for Genomic Interpretation Podcast Highlights How ‘In Silco Proficiency’ Testing Assesses Genetic Testing Accuracy

Presentation features John Pfeifer MD, PhD, Professor of Pathology and Immunology, Washington School of Medicine in St Louis


Salt Lake, UT / PRWeb /  January 25, 2022 – The Center for Genomic Interpretation (CGI) continues hosting its cutting-edge Rising Tide Podcast series, which features nationally-recognized experts in precision medicine. In Episode 4, the CGI Podcast features an interview with John Pfeifer MD, PhD, Professor of Pathology and Immunology at Washington School of Medicine in St Louis.

“This podcast is a must for anyone who wants to better understand the testing landscape and ultimate accuracy of a wide-range of genetic/genomic tests,” notes Julie Eggington, MS, PhD, CGI’s CEO and co-founder.  “CGI has partnered with Dr. Pfeifer through ELEVATEGENETICS  BRILLIANT to use advanced in silico proficiency computerized testing protocols to evaluate next-generation sequencing (NGS) technology to help identify tests and labs that can correctly detect and report more complex variants and their impact on patient treatment plans.  The program can be used to evaluate hereditary or germline disease testing, as well as solid or liquid tumor profiling.”

This session, entitled “In Silico Proficiency Testing to Improve Quality and Accuracy in Clinical Genetics and Genomics,” focuses on the regulatory, accreditation and payer requirements that laboratories must use to validate the accuracy of tests, ideally before they are ordered by providers for their patients.  The podcast provides a detailed overview of some of the technical, political and bioinformatic trends associated with ensuring the accuracy of genetic/genomic testing. 

When asked why we should care about the need to validate genetic/genomic testing results and treatment recommendations, Dr. Pfeifer responds “you should care about (in silico proficiency testing) because the old saying that ‘what you don’t know can’t hurt you” is actually false.  What you don’t know can hurt you.”  In the Podcast, Dr. Pfeifer notes further:

Proficiency testing  is the external mechanism that various regulatory agencies and payers use to ensure that laboratories, if they do a test, are getting an accurate test result. Everyone should care about proficiency testing; not only physicians, but also patients who have submitted a specimen to a lab for next-generation sequencing analysis, whether in the setting of cancer or inherited disease. 

The importance of advanced proficiency testing for next generation sequencing discussed in the podcast is highlighted by findings in a recent peer reviewed publication co-authored by Dr. Pfeifer (https://doi.org/10.1093/ajcp/aqab164). The results of the study, which featured in silico proficiency testing samples, show that a significant proportion  of laboratory test offerings are missing clinically actionable variants.  The study also shows  that such deficiencies can be identified using in silico approaches just as well as conventional biologic samples.

Among other helpful insights in the podcast, Dr. Pfeifer describes the five parts associated with next-generation sequencing and why in silico proficiency can reduce the number of false positives and false negatives related to genomic/genetic testing.  The five steps of next generation sequencing clinical tests are typically:  

  1. Extracting nucleic acids, also known as the DNA and RNA, out of the tissue;
  2. Creating a so-called library to sequence the extracted group of molecules;
  3. Actual sequencing of the DNA and/or RNA molecules;
  4. Using bioinformatics to match the sample sequences with reference sequences of the human genome, which includes looking for variants and mutations; and
  5. Evaluating and reporting on the clinical significance of the variants and mutations.

Dr. Pfeifer also details the role that in silico proficiency can provide in assessing the significance, or lack thereof, regarding whether a targeted variant or mutation is properly classified by a laboratory, which in turn impacts patient treatment recommendations and health outcomes.  He notes there is a “very limited range of wet specimens and cell lines (and other biologic samples); there may be whole classes of variants that a laboratory’s bioinformatics tool isn’t very good at recognizing, simply because that tool has never seen those variants.”

One of the main takeaways when listening to the podcast is the observation that in silico proficiency testing is a game changer by relying on a more structured and systematic review of individual laboratory analysis and reporting capabilities.  Dr. Pfeifer notes clinicians are “busy taking care of patients (and) they may not be sure whether a specific laboratory’s next-generation sequencing test is highly accurate  for the class of variants they’re looking for.” CLIA and CAP accreditations fail to adequately ensure that next generation sequencing tests perform as advertised.

This is where programs like CGI’s ELEVATEGENETICs BRILLIANT Program comes in which leverages in silico proficiency testing review to implement a more scalable and robust methodology in a more cost-effective manner to assess the clinical validity of laboratory genetic/genomic findings.   

Don’t forget to tune in to this and future CGI Rising Tide Podcasts episodes.  The complimentary podcasts are hosted through YouTube and can be viewed here

For more information about CGI, see www.genomicinterpretation.org.  CGI is offering several unique ELEVATEGENETICS programs that establish meaningful and actionable pathways to improve genetic/genomic testing, analysis and reporting. For payers, ELEVATEGENETICS metrics offer unique evaluations when selecting and contracting with laboratories.  For laboratories, these programs offer a unique third-party review focusing on key aspects of the genetic/genomic testing process which can dramatically improve the accuracy of test findings.  For providers and consumers, CGI offers a number of resources to better understand the complex landscape of precision medicine. 

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The Center for Genomic Interpretationwww.genomicinterpretation.org

The Center for Genomic Interpretation (CGI) is an independent 501(c)(3) nonprofit organization with the mission to save and improve lives through encouraging careful stewardship of clinical genetics, genomics and precision medicine. Too frequently the precision medicine goals of patients and their providers are unknowingly thwarted by inaccurate or ineffective genetic or genomic testing. We facilitate the realization of value from among the confusing scramble of the new precision medicine era. The CGI team consists of clinical genetics and genomics scientific leaders, healthcare policy veterans, experienced business professionals, and others dedicated to helping stakeholders achieve the vision and promise of precision medicine.  CGI offers a range of programs and services targeted to all stakeholders including patients, providers, payers, pharmaceutical developers, policy makers and laboratories.