Figure 11. The majority existing methods target regions rich of cis-regulatory elements.

Existing methods predict CRMs based on their distance and conservation features. This fact limits their targets are regions rich of closely located and highly conserved cis-regulatory elements (green region) instead of real functional modular CRMs (pink regions). Consequently, they will miss out: those CRMs composed of elements not conserved in a same order, e.g. CRM 1; those CRMs not conserved, e.g. CRM 2; or those CRMs composed of further apart elements, e.g. CRM 3. At the same time, uncompleted regions within a CRM, or overlapped regions shared by more than one CRMs, could be predicted as a false positive, e.g. a false positive prediction composed of CRM 2 and part of CRM 3.