Expanding insights from in situ cryo-EM

The combination of cryo-electron tomography and subtomogram analysis affords 3D high-resolution views of biological macromolecules in their native cellular environment, or in situ. Streamlined methods for acquiring and processing these data are advancing attainable resolutions into the realm of drug discovery. Yet regardless of resolution, structure prediction driven by artificial intelligence (AI) combined with subtomogram analysis is becoming powerful in understanding macromolecular assemblies. Automated and AI-assisted data mining is increasingly necessary to cope with the growing wealth of tomography data and to maximize the information obtained from them. Leveraging developments from AI and single-particle analysis could be essential in fulfilling the potential of in situ cryo-EM. Here, we highlight new developments for in situ cryo-EM and the emerging potential for AI in this process.