Anders, LarsGuenther, Matthew G.Qi, JunFan, Zi PengMarineau, Jason J.Rahl, Peter B.Lovén, JakobSigova, Alla A.Smith, William B.Lee, Tong IhnBradner, James EYoung, Richard A.2014-11-032014Anders, L., M. G. Guenther, J. Qi, Z. P. Fan, J. J. Marineau, P. B. Rahl, J. Lovén, et al. 2014. “Genome-wide determination of drug localization.” Nature biotechnology 32 (1): 92-96. doi:10.1038/nbt.2776. http://dx.doi.org/10.1038/nbt.2776.1087-0156http://nrs.harvard.edu/urn-3:HUL.InstRepos:13347537A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide new and important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. We show how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. These methods provide a powerful approach to enhance understanding of therapeutic action and characterize the specificity of chemical entities that interact with DNA or genome-associated proteins.en-USJournal Article2014-11-0310.1038/nbt.2776