Gene-centered identification of cis-regulatory islands highlights regulatory landscapes complementary to motif-centric approaches

Cis-regulatory elements constitute a fundamental layer of gene regulation, yet their computational identification has largely relied on transcription factor (TF)-centric frameworks that assume genome-wide background normalization and explicit TF binding models. While effective at the genome scale, such assumptions are less suitable for gene-centered analyses, where local sequence composition defines the relevant regulatory context. Here, we introduce a TF-independent observational framework for