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Cryo-electron tomography (cryo-ET) enables the analysis of biological samples in situ, revealing the complex interplay that shapes (sub)cellular architecture. Across the cryo-ET workflow, diverse forms of contextual information-from experimental metadata to spatial organization and particle-specific annotations-can inform the experimental design, guide computational approaches, and deepen the interpretation of tomograms. In this review, we highlight recent advances in contextual analysis that complement and enhance commonly used cryo-ET workflows, while also expanding their scope. Examples range from sample preparation to data analysis aided by molecular dynamics simulations. Together, they illustrate how different notions of context enrich in situ investigations and allow cryo-ET to extend beyond high-resolution structure determination toward a more comprehensive understanding of cellular environments.
Schreiber et al. (Wed,) studied this question.