Co-profiling (whole transcriptome and epigenome) of intact tissue to understand gene regulatory networks

Project Summary The relation between structure and function in tissues is the cornerstone of tissue biology and pathology. To address the need for analysis of intact tissue, many methods have emerged for spatial molecular profiling. Unique among spatial biology platforms, AtlasXomics’ microfluidics-based platform helps basic and translational researchers to understand and address the epigenetic dysregulation that underlies many diseases including cancer and neurodegenerative diseases such as Alzheimer’s and ALS. The large data sets generated by the new epigenomic assays can be integrated with data from single cell methods and larger data sets describing disease states. These data sets are valuable because therapies for cancer and neurodegenerative diseases are shifting from broad-brush approaches that have failed to meet expectations due to patient heterogeneity. More targeted treatments for likely responders creates demand for data that is presented in a form that informs disease mechanisms. Cell’s networks, phenotypic and functional state is jointly regulated at multiple levels involving genome, epigenome, transcriptome, proteome, and metabolome. Assessment of one modality at a time provides an incomplete representation of cellular identity and is inadequate to understand biological systems and their underlying regulatory mechanisms. There are no spatial epigenomics assays except for the one offered by AtlasXomics. This is the first product to be developed from the Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq) platform. The hypothesis is that the technology developed in an academic lab for co-profiling can be transferred to other labs using the Company’s new chip designs that are easier to use. Reductions in exposure to dust and required cleaning time by 90% should facilitate the democratized use of the assay. The Company already has established a data portal with interactive visualization tools and website for reviewers to access the processed data generated by DBiT-seq experiments from collaborators and customers. Raw and processed data generated by this STTR will be made available through the data portal tor reviewers (before publication) and the public to access data generated by this STTR (after publication). Twenty investigators will be offered the opportunity to use the new software tools for co- profiling service and to explore the curated data sets and provide feedback with a user satisfaction survey (Likert scale) to assess the analysis and viewing of epigenome and transcriptome data. In Phase II, we aim at launching commercial kits to existing customers of the single modality assay and to new customers. These new products will enable dual and eventually tri-omic same-section spatial co-profiling (transcriptome, epigenome, and proteome).