{"doi":"10.1101/191056","title":"Reconstruction of developmental landscapes by optimal-transport analysis of single-cell gene expression sheds light on cellular reprogramming","abstract":"Understanding the molecular programs that guide cellular differentiation during development is a major goal of modern biology. Here, we introduce an approach, WADDINGTON-OT, based on the mathematics of optimal transport, for inferring developmental landscapes, probabilistic cellular fates and dynamic trajectories from large-scale single-cell RNA-seq (scRNA-seq) data collected along a time course. We demonstrate the power of WADDINGTON-OT by applying the approach to study 65,781 scRNA-seq profiles collected at 10 time points over 16 days during reprogramming of fibroblasts to iPSCs. We construct a high-resolution map of reprogramming that rediscovers known features; uncovers new alternative cell fates including neuraland placental-like cells; predicts the origin and fate of any cell class; highlights senescent-like cells that may support reprogramming through paracrine signaling; and implicates regulatory models in particular trajectories. Of these findings, we highlight Obox6 , which we experimentally show enhances reprogramming efficiency. Our approach provides a general framework for investigating cellular differentiation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2017,"id":8203,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2017-09-27","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":72472,"name":"Jian Shu","orcid":"0000-0002-2938-4218","position":1,"is_corresponding":false},{"id":2687,"name":"Marcin Tabaka","orcid":"0000-0002-6166-2820","position":2,"is_corresponding":false},{"id":6114,"name":"Brian Cleary","orcid":"0000-0003-0825-7129","position":3,"is_corresponding":false},{"id":42114,"name":"Vidya Subramanian","orcid":null,"position":4,"is_corresponding":false},{"id":72473,"name":"Aryeh Solomon","orcid":"0000-0001-7647-5465","position":5,"is_corresponding":false},{"id":29935,"name":"Siyan Liu","orcid":"0000-0002-5091-7031","position":6,"is_corresponding":false},{"id":72474,"name":"Stacie Lin","orcid":null,"position":7,"is_corresponding":false},{"id":72475,"name":"Peter Berube","orcid":"0000-0002-9597-7716","position":8,"is_corresponding":false},{"id":72476,"name":"Lia Lee","orcid":null,"position":9,"is_corresponding":false},{"id":15880,"name":"Jenny Chen","orcid":"0000-0002-2992-4771","position":10,"is_corresponding":false},{"id":72477,"name":"Justin Brumbaugh","orcid":"0000-0002-9605-2010","position":11,"is_corresponding":false},{"id":72478,"name":"Philippe Rigollet","orcid":"0000-0002-1554-8912","position":12,"is_corresponding":false},{"id":56485,"name":"Konrad Hochedlinger","orcid":"0000-0001-5811-5386","position":13,"is_corresponding":false},{"id":30028,"name":"Rudolf Jaenisch","orcid":"0000-0002-2540-7099","position":14,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":15,"is_corresponding":false},{"id":18887,"name":"Matthew E. Hurles","orcid":"0000-0002-2333-7015","position":16,"is_corresponding":false},{"id":48123,"name":"Geoffrey Schiebinger","orcid":"0000-0002-8290-7997","position":0,"is_corresponding":true}],"reference_count":124,"raw_metadata":null,"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":[]}