Scalable and quantitative chromatin profiling from formalin-fixed paraffin-embedded samples

PROJECT SUMMARY Cellular function is regulated at the chromatin level by epigenomic features, including histone post- translational modifications (PTMs) and chromatin-associated proteins (CAPs). The development of tools for genomic mapping has ushered in a new era of epigenetic research, placing histone PTMs and CAPs in the spotlight as novel biomarkers and therapeutic targets. Despite this progress, leveraging epigenomics for clinical studies has been hindered by a lack of high-performance genomic mapping assays that are compatible with formalin-fixed paraffin-embedded (FFPE) tissue, due to DNA damage that is incurred during the FFPE process. FFPE is the gold-standard method for preservation and storage of clinical samples, with millions of samples from diverse tissues and pathologies banked annually. While other FFPE sample-compatible chromatin mapping assays have been developed, these approaches are unsuitable for clinical research due to limited sensitivity, throughput, and / or resolution of specific chromatin features. As such, FFPE samples represent a largely untapped goldmine for clinical genomic analyses. Development of a next-generation chromatin profiling assay for FFPE samples would unlock access to disease-related epigenetic information within these clinical samples, enabling novel biomarker discovery / validation and insights into therapeutical targeting of epigenomic targets. To meet this need, EpiCypher is partnering with Dr. Kami Ahmad (Fred Hutchinson Cancer Research Center) to develop CUTANA-FFPETM, a first-in-class low input genomic mapping tool for the analysis of FFPE clinical samples. In Phase I, we developed the CUTANA-FFPE approach and successfully applied it to identify tumor-specific regulatory elements in FFPE samples, demonstrating greatly improved performance compared to existing assays and the transformative potential of this technology to advance clinical research. In Phase II, we will prepare for commercial launch by developing standard operating procedures (SOPs) for processing FFPE samples and validating the assay for diverse targets. Next, we will demonstrate the clinical utility of this novel technology by expanding the approach to various tissue types, optimizing in situ target visualization, and defining quality control parameters for banked FFPE samples. Finally, we will integrate data analysis pipelines into a user-friendly and HIPAA-compliant bioinformatics portal, assemble CUTANA-FFPE beta kits, and apply CUTANA-FFPE to map diverse targets in FFPE samples from diseased clinical tissue. Market availability of this assay would be transformative for clinical research by enabling chromatin profiling in FFPE tissue, supporting next-generation biomarker discovery and drug development.