ABSTRACT The parent award aims to study transcriptional and epigenetic mechanisms of cellular survival and adaptation under stress using lineage barcoding, single-cell multiomics, and spatial transcriptomics. Budget cuts have limited the number of cancer models and cell lines studied, potentially impacting the generalizability of the findings. This Equipment Supplement requests funds to purchase an Element AVITI System, a transformative next-generation sequencing platform that will overcome these limitations and enhance the impact of the parent award. The AVITI System's unique Avidity Base Chemistry delivers high-quality sequencing data while dramatically reducing costs. Its acquisition will enable lineage tracing and sequencing on more cancer models and stressors, improve data quality for precise barcode assignment, and accelerate experimental workflows. We are requesting $250,000 towards the total cost of $290,000, with the Shaffer lab covering the remaining $40,000 (see letter). This purchase will have the greatest impact on the research if supported now at the start of the award. The AVITI System will be housed in the Shaffer lab, which has extensive experience in operating similar equipment. Cost savings from transitioning to the AVITI platform will allow the project to achieve more of its initial goals without exceeding the sequencing consumables budget. Long-term sustainability for the service contract expenses will be ensured through cost-sharing agreements with other labs, UPenn Institutes, and departments.