Research Project
10147659
Commercialization of a highly-sensitive, scalable and low-input compatible kit-based solution for discovery of translocations from FFPE tumor biopsies Arima Genomics Project Summary/Abstract Despite decades of research, cancer takes the lives of nearly 600,000 people every year in the US. The cancer research community has made key advancements towards improving the precision of cancer diagnosis and recently substantial efforts have been put forth into the genetic profiling of tumors. Specifically, efforts have been focused on developing methods to profile genetic alterations such as translocations that are prognostic in cancer. Knowledge of an individual's translocation profile can be used to uncover the mechanistic basis of cancer, accelerating cancer research towards development of new precision therapies. Current standard, including NGS, are limited in their ability to characterize translocations. This is because for NGS (WGS or gene panel seq.) to profile translocations, breakpoint-spanning reads are needed and NGS does not enrich for such reads. FISH enriches for breakpoint info by capturing spatial conformation of the genome within cells and but it has limited utility due to its low-throughput nature and its requirement of apriori info of the translocation partners. Spectral Karyotyping (SKY) needs living cells and cannot be performed on FFPE samples, which is a major sample type for cancer samples. Altogether, a method that is (a) high-throughput along the lines of NGS; (b) enriches translocations along the lines of FISH; (c) not requiring apriori indo of translocating partners to enable promiscuous translocation detection; and (d) compatible with FFPE samples ? would result in a highly sensitive and scalable solution for translocation discovery. We satisfy the unmet need via a leapfrog solution. We use HiC to capture conformation on the lines of FISH and couple it with NGS (HiC-Seq) to detect translocations at high sensitivity, high precision, high PPV and low FP. Our team has unmatchable expertise in the science of HiC and its commercialization. Specifically, we commercialized Arima-HiC kits in 2018 for studying conformation in the context of Epigenetics research and generated $1.2M in revenue in the 1st year of commercialization with 200+ customers, all from 1 sales executive. However, these kits are not compatible to FFPE, is manual, labor- and time-intensive and cannot handle batches of >10-20 samples at a time ? to enable broad adoption toward cancer research, we have shown the development a boxed kit, the ?T-Seq Kit?, based on enhanced HiC optimized for performance, speed, ease of use that is compatible to low-input FFPE, fresh and frozen samples. We validate the technology development from sample to insight in a patient-derived FFPE GIST biopsy and demonstrate that we can sensitively profile translocations even from low tumor purity samples (or low MAF). As part of this direct-2-phase II program, we propose to further develop our technology into a robust kit-based ?T-Seq Solution?, comprising same day 8hr sample to sequencing, full 96-plate automated and versatile HiC protocols (to all sample types) that is compatible with existing NGS (ILMN) workflow for customer convenience and bundled with cloud-based push-button bioinformatics equipped with tools for sensitive genome-wide and targeted translocation discovery. We also propose rigorous and essential product development experiments, to ensure commercialization of a robust, premium-performance kit-based product. Upon successful completion of the technical and commercial developments in Aims 1 & 2, we propose to benchmark and validate the sample-to-insight T-Seq Solution through collaboration and prototype (beta) kit and bioinformatics evaluations with key opinion leaders (KOLs) across customer segments of large sequencing centers, academic labs, and pharma.
