Topologically associating domains (TADs) are contiguous segments of the genome where the genomic elements are in frequent contact with each other. The TAD Map (bioRxiv preprint) provides a consensus estimate of the TAD layout for human and mouse, aggregated from multiple experimental datasets. Contextual similarity, a powerful embedding-based metric derived from single-cell foundation models, reveals that genes within the same TAD are more functionally related, offering insights into potential mechanisms. Our framework generates testable hypotheses by leveraging this metric to compare TAD and non-TAD gene pairs across cell states, diseases, and aging. This approach is detailed in the bioRxiv preprint, Tracing the Shared Foundations of Gene Expression and Chromatin Structure, by Huan Liang, Bonnie Berger, and Rohit Singh.