The framework’s ability to distinguish between general promoter biology (Model A) and TSp regulatory mechanisms (Model B) provides a systematic approach to dissect the molecular basis of healthy tissues, study its relevance in disease biology, particularly in complex diseases like cancer and neurodegeneration, where there is known TSp dysregulation of normal regulatory programs [Bianchi et al., 2020, Dos Santos et al., 2023, Sonawane et al., 2017]. This evidence concerns the gene THBS1 and cancer.