{"doi":"10.1101/2022.03.08.483436","title":"Nanobody-tethered transposition allows for multifactorial chromatin profiling at single-cell resolution","abstract":"Chromatin states are functionally defined by a complex combination of histone modifications, transcription factor binding, DNA accessibility, and other factors. However, most current single-cell-resolution methods are unable to measure more than one aspect of chromatin state in a single experiment, limiting our ability to accurately measure chromatin states. Here, we introduce nanobody-tethered transposition followed by sequencing (NTT-seq), a new assay capable of measuring the genome-wide presence of multiple histone modifications and protein-DNA binding sites at single-cell resolution. NTT-seq utilizes recombinant Tn5 transposase fused to a set of secondary nanobodies (nb). Each nb-Tn5 fusion protein specifically binds to different immunoglobulin-G antibodies, enabling a mixture of primary antibodies binding different epitopes to be used in a single experiment. We apply bulk- and single-cell NTT-seq to generate high-resolution multimodal maps of chromatin states in cell culture and in cells of the human immune system, demonstrating the high accuracy and sensitivity of the method. We further extend NTT-seq to enable simultaneous profiling of cell-surface protein expression alongside multimodal chromatin states to study cells of the immune system.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297043,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":52005,"name":"Stephanie Hao","orcid":"0000-0002-1700-9699","position":1,"is_corresponding":false},{"id":580312,"name":"Bingjie Zhang","orcid":"0000-0002-0535-0371","position":2,"is_corresponding":false},{"id":786610,"name":"Levan Mekerishvili","orcid":"0000-0002-4792-5356","position":3,"is_corresponding":false},{"id":68986,"name":"Dan A. Landau","orcid":"0000-0003-2346-9541","position":4,"is_corresponding":false},{"id":109624,"name":"Silas Maniatis","orcid":"0000-0002-0888-1477","position":5,"is_corresponding":false},{"id":311859,"name":"Rahul Satija","orcid":"0000-0001-9448-8833","position":6,"is_corresponding":false},{"id":810342,"name":"Ivan Raimondi","orcid":"0000-0002-9522-2794","position":7,"is_corresponding":false},{"id":158,"name":"Tim Stuart","orcid":"0000-0002-3044-0897","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:21.257700Z","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":[]}