ChExAlign is a computational framework that aligns ChIP-exo crosslinking patterns from multiple proteins across a set of regulatory regions, and which detects and quantifies protein-DNA crosslinking events within the aligned profiles. The output of the alignment approach is a set of composite profiles that represent the crosslinking signatures of the complex across analyzed regulatory regions. We then use a probabilistic mixture model to deconvolve individual crosslinking events within the aligned ChIP-exo profiles, enabling consistent measurements of protein-DNA crosslinking strengths across multiple proteins.