{"doi":"10.1038/ncomms8440","title":"Context influences on TALE–DNA binding revealed by quantitative profiling","abstract":"Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE-DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000-20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE-DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design.","journal":"Nature Communications","year":2015,"id":2007,"datarank":1.4753045422605182,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.9377767014921018,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.9377767014921018,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":34,"citers_with_citation_signal":29,"citers_with_endowment":29,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2015-06-11","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23563,"name":"Luis A. Barrera","orcid":null,"position":1,"is_corresponding":false},{"id":23564,"name":"Deepak Reyon","orcid":"0000-0002-0133-1413","position":2,"is_corresponding":false},{"id":23565,"name":"Jeffry D. Sander","orcid":"0000-0002-4370-3182","position":3,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":4,"is_corresponding":false},{"id":23566,"name":"J. Keith Joung","orcid":"0000-0001-5630-5645","position":5,"is_corresponding":false},{"id":23567,"name":"Martha L. Bulyk","orcid":null,"position":6,"is_corresponding":false},{"id":23568,"name":"Luis Barrera","orcid":"0000-0003-0612-6416","position":7,"is_corresponding":false},{"id":23562,"name":"Julia M. Rogers","orcid":"0000-0001-6518-5470","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}