{"doi":"10.1093/nar/gkaf101","title":"Generalization of the sci-L3 method to achieve high-throughput linear amplification for replication template strand sequencing, genome conformation capture, and the joint profiling of RNA and chromatin accessibility","abstract":"Single-cell combinatorial indexing (sci) methods have addressed major limitations of throughput and cost for many single-cell modalities. With the incorporation of linear amplification and three-level barcoding in our suite of methods called sci-L3, we further addressed the limitations of uniformity in single-cell genome amplification. Here, we build on the generalizability of sci-L3 by extending it to template strand sequencing (sci-L3-Strand-seq), genome conformation capture (sci-L3-Hi-C), and the joint profiling of RNA and chromatin accessibility (sci-L3-RNA/ATAC). We demonstrate the ease of adapting sci-L3 to these new modalities by only requiring a single-step modification of the original protocol. As a proof of principle, we show our ability to detect sister chromatid exchanges, genome compartmentalization, and cell state-specific features in thousands of single cells. We anticipate sci-L3 to be compatible with additional modalities, including DNA methylation (sci-MET) and chromatin-associated factors (CUT&Tag), and ultimately enable a multi-omics readout of them.","journal":"Nucleic Acids Research","year":2025,"id":520635,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":556356,"name":"Yi Yin","orcid":"0000-0003-0963-2672","position":1,"is_corresponding":false},{"id":551600,"name":"Peter Chovanec","orcid":"0000-0001-8066-1893","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:49:28.470782Z","pmid":"39997216","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":[]}