From Splicing Graph to RNA Medicine

Abstract

Diagnosing rare diseases remains a major challenge in medicine despite widespread clinical testing. While each condition is  uncommon, rare diseases collectively affect more than 300 million people worldwide across over 7,000 disorders. High-throughput DNA sequencing, including whole-exome and whole-genome sequencing, has become routine in both clinical and research settings. Yet diagnostic yield remains modest, leaving millions of patients without a molecular diagnosis. Although DNA sequencing can identify candidate variants, it often cannot determine how those variants disrupt RNA processing and gene function.

In this lecture, the speaker will describe the development of long-read RNA sequencing strategies for rare disease diagnosis. The STRIPE platform enables deep sequencing of full-length RNAs from customized disease gene panels. This approach allows simultaneous detection of sequence variants, aberrant RNA processing events, allele-specific effects on gene dosage, and parent-of-origin information. Applied to more than 500 patients across multiple rare disease groups, STRIPE emerges as a powerful, adaptable, and scalable strategy with broad potential to improve clinical variant interpretation and advance genetic diagnosis of rare diseases.

Overall, this work connects technological and computational advances in isoform-resolved RNA sequencing to RNA-based precision diagnostics and therapeutics for rare diseases.

About the Speaker

Prof. XING Yi is the Francis West Lewis Endowed Chair, Founding Director of the Center for Computational and Genomic Medicine, and the Executive Director of the Department of Biomedical and Health Informatics at the Children’s Hospital of Philadelphia (CHOP). Prof. Xing is also a Professor of Pathology and Laboratory Medicine at the University of Pennsylvania. He has published extensively in bioinformatics, genomics, and RNA biology. His current work integrates computational biology, biomedical data science, RNA genomics, human genetics, precision medicine, and immuno-oncology.

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