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While quantum computers promise to solve some scientifically and commercially valuable problems thought intractable for classical machines, delivering on this promise will require a large-scale quantum machine. Understanding the impact of architecture design choices for a scaled quantum stack for specific applications, prior to full realization of the quantum system, is an important open challenge. To this end, we develop a framework for quantum resource estimation, abstracting the layers of the stack, to estimate resources required across these layers for large-scale quantum applications. Using a tool that implements this framework, we assess three scaled quantum applications and find that hundreds of thousands to millions of physical qubits are needed to achieve practical quantum advantage. We identify three qubit parameters, namely size, speed, and controllability, that are critical at scale to rendering these applications practical. A goal of our work is to accelerate progress towards practical quantum advantage by enabling the broader community to explore design choices across the stack, from algorithms to qubits.