Scalable spatiotemporal-omics platform

PROJECT SUMMARY/ABSTRACT Accurately predicting the clinical efficacy of drug candidates during pre-clinical drug discovery has the power to revolutionize the biopharmaceutical industry. To this end, “profiling” techniques have gained rapid adoption in the drug discovery processes because these techniques can assess a broad range of features – such as gene expression or spatial features – offering a holistic understanding of a drug’s potential impact. The collected profile data can be utilized to identify and validate new drug targets, elucidate mechanisms of action, pinpoint promising drug candidates, and reposition drugs, ultimately providing multi-faceted benefits during pre-clinical drug discovery. However, a critical limitation of current profiling techniques is that they fail to assess how drugs affect spatiotemporal properties by altering the genomic, epigenomic, transcriptomic, and proteomic underpinnings of cells. This is a critical limitation because many disease abnormalities and drugs’ therapeutic effects manifest via changing the spatiotemporal properties of cells. Therefore, linking these cellular spatiotemporal properties to underlying omics data can provide a powerful insight into drug mechanism and function. While spatial omics platforms do exist, their prohibitive costs and limited utility in live cell cultures make them unsuitable for pre-clinical drug discovery. To address this issue, Imagen Bioworks is developing an innovative spatiotemporal- omics workflow suitable for pre-clinical drug discovery. This workflow, SPOTlight-omics, is a cost-effective technique that can isolate interesting spatiotemporal phenotypes from live cell cultures. We plan to use the SPOTlight platform to isolate a subpopulation of cells showing disease-relevant spatiotemporal properties after drug exposure and subject the isolated cells to subsequent omics assays. Two critical hurdles must be overcome before SPOTlight-omics is ready to be commercialized: (Aim 1) Achieving faster optical tagging and enabling cell sorting of multiple phenotypic subgroups. Achieving Aim 1 will provide significant timesaving, increase in cell isolation yield, and enable greater types of downstream omics assays. (Aim 2) Demonstrating the feasibility and the utility of using SPOTlight-omics to profile the effects of drugs on spatiotemporal properties. Overall, our proposal leverages recent advancements in computer vision, spatial/temporal omics, multi-omics, and drug profiling. Successful completion of this proposal will lead to a new drug profiling technique that our biopharma customers can utilize to gain additional insights into the function of drugs during pre-clinical drug discovery.