We applied WaveTAD to multiple datasets from Drosophila, mouse, and humans to illustrate new biological insights that our more sensitive and quantitative approach provides, such as the widespread presence of embryonic 3D organization before zygotic genome activation, the effect of multiple CTCF units on the stability of loops and TADs, and the association between gene expression and TAD structures in COVID-19 patients or sex-specific transcription in Drosophila. The gene discussed is CTCF; the disease is COVID-19.