Revolutionary RNA Sequencing Test Set to Transform Genetic Diagnostics

Overview

Recent advancements in the realm of genetic diagnostics have led to the development of a groundbreaking RNA sequencing test, marking a significant leap forward in the diagnosis of Mendelian diseases. A team of researchers at Baylor College of Medicine's Medical Genetics and Multiomics Laboratory has successfully validated the first clinical RNA sequencing test designed for whole-transcriptome analysis of genetic disorders. This innovation aims to broaden the application of RNA sequencing beyond its traditional targeted analysis.

The findings, published in The American Journal of Human Genetics, detail a comprehensive pipeline for transcriptome sequencing that can be utilized in clinical settings. Traditionally, RNA sequencing has been limited to specific gene analyses; however, this new validation represents a pioneering effort to harness the complete capabilities of RNA sequencing for clinical diagnostics.

According to Dr. Pengfei Liu, a leading researcher in the study, the establishment of this test marks a historic moment in clinical diagnostics. Previously, RNA sequencing was primarily confined to targeted testing. The collaboration with the College of American Pathologists (CAP) was crucial in creating the first whole-transcriptome sequencing activity that can now be reported as a standard assay.

The RNA sequencing test employs samples obtained from fibroblasts or blood, focusing on identifying anomalies in gene expression and splicing patterns. In validating the test, the research team analyzed a total of 130 samples, which included 40 samples with confirmed molecular diagnoses and 90 control samples from healthy individuals. They developed benchmarks for gene expression and splicing based on RNA sequencing data from a lymphoblastoid sample available through the Genome in a Bottle Consortium, establishing reference ranges for each gene using this control data.

To evaluate the clinical efficacy of the test, the team assessed samples with previously confirmed diagnostic findings from the Undiagnosed Diseases Network (UDN). The results affirmed the test's capability to detect significant RNA findings, utilizing both transcriptome-driven and DNA-driven analytic approaches. This dual analysis approach showcases the test's potential to enhance molecular diagnostics significantly.

This new RNA sequencing test is the first to be launched by the Medical Genetics and Multiomics Laboratory and is now available for clinical application within the Undiagnosed Diseases Network.