{"doi":"10.1101/2025.09.22.677806","title":"SpliceUp: Predicting\n                  <i>SF3B1</i>\n                  mutations in individual cells via aberrant splice site activation from scRNA-seq data","abstract":"<jats:p>\n                  Myeloid neoplasms (MN) are clonal heterogeneous disorders initiated by somatic driver mutations in hematopoietic stem and progenitor cells (HSPCs). Among the most common are mutations in RNA splicing factors, which exert pleiotropic effects but are difficult to study due to altered hematopoietic differentiation and the inability to specifically isolate mutant HSPCs. Single-cell transcriptomics offers a powerful framework to dissect mutant cell states, yet direct genotyping is hampered by data sparsity and often requires costly, labor-intensive approaches. To overcome this limitation, we developed SpliceUp, a computational tool that identifies splice factor-mutant cells through their aberrant RNA splicing signatures. Applied to\n                  <jats:italic>SF3B1</jats:italic>\n                  -mutant samples, SpliceUp exploits cryptic 3’ splice site usage and exon-skipping events to achieve more than a 7-fold increase in mutant cell detection from low-coverage 10x Genomics datasets. Differential expression analysis revealed cell typespecific programs, including MHC-II upregulation in\n                  <jats:italic>SF3B1</jats:italic>\n                  -mutated HSCs and enhanced RNA translation in\n                  <jats:italic>SF3B1</jats:italic>\n                  -mutated erythroid precursors.\n                </jats:p>","journal":null,"year":null,"id":647312,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1073715,"name":"Karin D. Prummel","orcid":"0000-0001-6077-6407","position":1,"is_corresponding":false},{"id":1588149,"name":"Borhane Guezguez","orcid":"0000-0002-1474-8074","position":2,"is_corresponding":false},{"id":14368,"name":"Eva Hellström‐Lindberg","orcid":"0000-0002-7839-3743","position":3,"is_corresponding":false},{"id":1246973,"name":"Pedro Luís Moura","orcid":"0000-0002-0493-5394","position":4,"is_corresponding":false},{"id":4985,"name":"Judith B. Zaugg","orcid":"0000-0001-8324-4040","position":5,"is_corresponding":false},{"id":1686389,"name":"Maksim Kholmatov","orcid":"0000-0002-4201-8124","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"SpliceUp: Predicting\n                  <i>SF3B1</i>\n                  mutations in individual cells via aberrant splice site activation from scRNA-seq data","abstract":"<jats:p>\n                  Myeloid neoplasms (MN) are clonal heterogeneous disorders initiated by somatic driver mutations in hematopoietic stem and progenitor cells (HSPCs). Among the most common are mutations in RNA splicing factors, which exert pleiotropic effects but are difficult to study due to altered hematopoietic differentiation and the inability to specifically isolate mutant HSPCs. Single-cell transcriptomics offers a powerful framework to dissect mutant cell states, yet direct genotyping is hampered by data sparsity and often requires costly, labor-intensive approaches. To overcome this limitation, we developed SpliceUp, a computational tool that identifies splice factor-mutant cells through their aberrant RNA splicing signatures. Applied to\n                  <jats:italic>SF3B1</jats:italic>\n                  -mutant samples, SpliceUp exploits cryptic 3’ splice site usage and exon-skipping events to achieve more than a 7-fold increase in mutant cell detection from low-coverage 10x Genomics datasets. Differential expression analysis revealed cell typespecific programs, including MHC-II upregulation in\n                  <jats:italic>SF3B1</jats:italic>\n                  -mutated HSCs and enhanced RNA translation in\n                  <jats:italic>SF3B1</jats:italic>\n                  -mutated erythroid precursors.\n                </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"EC H2020 MSCA-ITN Project ENHPATHY","grant_id":"860002","title":null},{"funder_name":"SNSF","grant_id":"P2ZHP3_199669","title":null},{"funder_name":"EMBO","grant_id":"538-2021","title":null},{"funder_name":"Myelodysplastic Syndromes Foundation, Inc.","grant_id":"1142079","title":null},{"funder_name":"European Hematology Association","grant_id":"Topic-In-Focus Advanced Research Grant 2025","title":null},{"funder_name":"Dr. Åke Olsson foundation","grant_id":"Dnr 2024-00303","title":null},{"funder_name":"Alex and Eva Wallström foundation","grant_id":"Dnr 2024-00311","title":null},{"funder_name":"KI Research Foundation grant","grant_id":"Dnr 2024-02330","title":null},{"funder_name":"European Union","grant_id":"101044873","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"199669","title":"Elucidating the molecular determinants in the remodeling of the bone marrow niche in AML, using single-cell multi-omics"},{"funder_name":"German Cancer Consortium (DKTK) Joint Funding Program","grant_id":"","title":null}],"total_grants":11,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/09/24/2025.09.22.677806.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2025.09.22.677806","host_type":"publisher"},{"url":"https://europepmc.org/article/PPR/PPR1090441","host_type":"Europe_PMC"},{"url":"https://europepmc.org/api/fulltextRepo?pprId=PPR1090441&type=FILE&fileName=EMS209147-pdf.pdf&mimeType=application/pdf","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2025.09.22.677806","host_type":""}],"fields_of_study":["0206 medical engineering","02 engineering and technology"],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T17:57:20.659518Z","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":[]}