{"doi":"10.1101/2023.01.24.525264","title":"Delineating genotypes and phenotypes of individual cells from long-read single cell transcriptomes","abstract":"Abstract Single-cell nanopore sequencing of full-length mRNAs (scNanoRNAseq) is transforming singlecell multi-omics studies. However, challenges include computational complexity and dependence on short-read curation. To address this, we developed a comprehensive toolkit, scNanoGPS to calculate same-cell genotypes-phenotypes without short-read guidance. We applied scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell lines. Standalone, scNanoGPS accurately deconvoluted error-prone long-reads into single-cells and single-molecules. Further, scNanoGPS simultaneously accessed both phenotypes (expressions/isoforms) and genotypes (mutations) of individual cells. Our analyses revealed that tumor and stroma/immune cells often expressed significantly distinct combinations of isoforms (DCIs). In a kidney tumor, we identified 924 genes with DCIs involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Moreover, transcriptome-wide mutation analyses identified many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting critical roles of different populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":402625,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7089,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1021373,"name":"Lina Lu","orcid":"0000-0003-3138-1478","position":1,"is_corresponding":false},{"id":1021374,"name":"Rachel E. Kieser","orcid":"0000-0003-1820-0193","position":2,"is_corresponding":false},{"id":270655,"name":"Kazutaka Fukumura","orcid":"0000-0001-5975-4120","position":3,"is_corresponding":false},{"id":1021375,"name":"Timothy Pan","orcid":"0009-0006-4328-1174","position":4,"is_corresponding":false},{"id":399228,"name":"Hsiao‐Yun Lin","orcid":"0000-0002-8295-4339","position":5,"is_corresponding":false},{"id":647920,"name":"Jie Yang","orcid":"0000-0003-2241-5066","position":6,"is_corresponding":false},{"id":1022030,"name":"Eric L. Tong","orcid":null,"position":7,"is_corresponding":false},{"id":647813,"name":"GaHyun Lee","orcid":"0000-0002-8000-4663","position":8,"is_corresponding":false},{"id":230396,"name":"Yuanqing Yan","orcid":"0000-0002-0094-7726","position":9,"is_corresponding":false},{"id":14371,"name":"Jason T. Huse","orcid":"0000-0003-4514-0640","position":10,"is_corresponding":false},{"id":573951,"name":"Ruli Gao","orcid":"0000-0002-1137-4564","position":11,"is_corresponding":false},{"id":1021372,"name":"Cheng-Kai Shiau","orcid":"0000-0003-0883-8660","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:20:27.903246Z","pmid":"36778278","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":[]}