Periodic Reporting for period 1 - MultiCloneSeq (Single-Clone Multi-omics Sequencing for Cancer Diagnosis)
Período documentado: 2023-10-01 hasta 2025-03-31
Cancer remains a leading cause of death worldwide, yet current diagnostic tools fall short in sensitivity, comprehensiveness, and cost-effectiveness, especially when linking rare somatic mutations to functional consequences across individual cells. To address this, we developed MultiCloneSeq, a novel single-cell multi-omics technology that simultaneously profiles the full-length transcriptome and epigenome of individual cancer clones. MultiCloneSeq overcomes key limitations of current tools (e.g. 10x Genomics) by enabling full-length RNA capture, detecting non-polyadenylated transcripts, and improving sensitivity through clone-based amplification using microfluidics. It integrates three proprietary methods: CloneSeq for single-clone culture and sequencing, scrDSeq for full-length total RNA profiling, and a cost-effective drop-based assay for chromatin accessibility. Applied to lung carcinoma and soft-tissue sarcoma, MultiCloneSeq identified rare subpopulations, such as cancer stem-like cells and clinically relevant mutations (e.g. in EGFR), undetectable by standard methods. Compared to existing platforms, it reduces cost by 10-fold, paving the way for practical, high-resolution diagnostics. Originating from our ERC-funded SC-EpiCode project, this innovation addresses cellular heterogeneity by decoding gene expression and chromatin regulation. The PoC phase will expand patient sample cohorts, strengthen IP, and lay the groundwork for commercialization as a precision oncology tool for early cancer detection and personalized treatment strategies.
We have finalized the development of the individual technologies, namely, CloneSeq, single-cell full-length RNA sequencing in droplets, and single-cell chromatin DNA-based sequencing. A paper on CloneSeq has already been published in Developmental Cell, the full-length RNA sequencing study is currently under review in Nucleic Acids Research, and the chromatin profiling manuscript is in preparation. We have now begun working on the molecular protocol that will enable us to integrate all three approaches into a single, unified multi-omic technology.
We have submitted an IP application for our novel concept and potentially groundbreaking technology. To date, we have published one paper, have another manuscript under review, and a third currently in preparation. We are now beginning to work on our EIC Transition proposal, which we plan to submit in the upcoming call.