UC Irvine team develops innovative MESA liquid biopsy technologies for early disease detection and prognosis

Detecting diseases using readily accessible body fluids such as blood (commonly termed “liquid biopsy”) is often hailed as the “holy grail” in diagnostic medicine. The goal is to identify patients in early, treatable stages and enhance prognosis for more informed treatment decisions. Recent clinical trials indicate that the methylation of circulating cell-free DNA (cfDNA), which consists of degraded DNA fragments in the bloodstream —primarily from dying cells — has emerged as the most promising liquid biopsy biomarker.

Motivated by these findings, the Wei Li Lab of Computational Biomedicine at the University of California, Irvine, School of Medicine, led by Grace B. Bell Endowed Chair and Professor of Bioinformatics Wei Li, PhD, recently developed Multimodal Epigenetic Sequencing Analysis (MESA), an innovative, patent-pending (UC Case No.2022-964-1) technique that captures and integrates several epigenetic modalities, namely cfDNA methylation and nucleosome occupancy via targeted enzymatic methyl-sequencing (EM-seq). Multiple lines of evidence have suggested that the MESA integration of multiple distinct epigenetic modalities can significantly increase the accuracy of disease detection.

MESA’s first successful application is detailed in a recent study published in Genome Medicine that details this non-invasive colorectal cancer detection. Looking ahead, the Wei Li Lab is well poised to make significant strides in developing blood biomarkers to meet critical unmet clinical needs, leveraging collaborations with numerous UC Irvine physicians and scientists. Current ongoing projects for the lab include:

• A breast cancer prognosis study using approximately 2,600 samples with over 20 years of follow-up in partnership with Hoda Anton-Culver, PhD, professor of medicine and director of the UCI Genetic Epidemiology Research Institute.
• A prostate cancer prognosis project analyzing over 200 samples with comprehensive pathological and clinical data in collaboration with Xiaolin Zi, PhD, professor of urology.
• The early detection of neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS), utilizing over 2,000 blood and cerebrospinal fluid (CSF) samples in collaboration with Albert La Spada, MD, PhD, professor of pathology and neurology; Parkinson’s disease with Nicolás M. Phielipp, MD, associate professor of neurology; and Huntington’s disease with Leslie Thompson, PhD, Donald Bren and Chancellor's Professor of psychiatry and human behavior.
• Liquid biopsy diagnosis research for suicide prevention for major depression patients in collaboration with Adolfo Sequeira, PhD, psychiatry and human behavior researcher.

The study was done in collaboration with Helio Genomics, an AI-driven healthcare company specializing in diagnostics technology and test development for cancer detection.