NESSI-Seq: novel cfDNA methylation assays for biomarker discovery and precision medicine

Abstract The emergence and clinical integration of genetic and epigenetic biomarkers is revolutionizing diagnostics and precision medicine. However, the low concentrations and fragmented nature of many DNA species pose significant challenges for the widespread adoption of many sequencing-based assays. Conventional methods for sequencing and analyzing DNA methylation suffer from chemical DNA damage and amplification biases, obscuring true biological signals, especially in inherently damaged and fragmented DNA, like cell-free DNA (cfDNA). To address these challenges, Wasatch BioLabs introduces whole-genome sequencing via NESSI-Seq (wgNESSI-Seq), a proprietary technology designed to sequence and analyze methylation without conversion or amplification biases. NESSI-Seq leverages proprietary library preparation technology to improve sensitivity, throughput, and data quality and nanopore sequencing to capture the benefits of native sequencing and single-molecule analysis. By maintaining the integrity of native epigenetic information, NESSI-Seq provides a more accurate reflection of underlying biology. The whole-genome approach enables the comprehensive characterization of all CpGs for biomarker discovery and other clinical applications, broadening analysis compared to traditional arrays. The clinical utility of wgNESSI-Seq for cfDNA has been demonstrated in several tests, including one assessing infertility and potential genetic causes and another identifying cfDNA derived from brain neurons as biomarkers of neurodegeneration in diseases like Alzheimer’s and Parkinson’s. These tests incorporate cfDNA cell-of-origin methylation analyses and the detection of pathogenic variants. wgNESSI-Seq’s applications are expanding to pathogen infections, autoimmune conditions, and other therapeutic areas. In oncology, wgNESSI-Seq has been used to identify cancer biomarkers in gDNA from cryo- and formalin-preserved tissues, which face similar challenges as cfDNA — extensive DNA damage and fragmentation. NESSI-Seq improves throughput, eliminates conversion and amplification biases, and enables comprehensive assessment of sequence and methylation with single-molecule resolution. This paradigm shift in DNA analysis enhances accuracy, sensitivity, and scalability, facilitating a deeper understanding of disease mechanisms and paving the way for precise diagnostics and personalized treatment strategies in precision medicine.  Biography With a robust background in genetics, epigenetics, and bioinformatics research and development, Chad has co-founded three companies dedicated to enhancing the accessibility of high-impact DNA sequencing-based technologies and diagnostics. Through his combined roles, he significantly contributes to the development of genomic technologies aimed at addressing critical healthcare challenges. Pollard's efforts focus on creating innovative diagnostic tools and providing strategic business leadership to target key gaps in global healthcare systems.