{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:44:30Z","timestamp":1783701870197,"version":"3.55.0"},"posted":{"date-parts":[[2023,11,15]]},"group-title":"Bioinformatics","reference-count":150,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Biological insights often depend on comparing conditions such as disease and health, yet we lack effective computational tools for integrating single-cell genomics data across conditions or characterizing transitions from normal to deviant cell states. Here, we present Decipher, a deep generative model that characterizes derailed cell-state trajectories. Decipher jointly models and visualizes gene expression and cell state from normal and perturbed single-cell RNA-seq data, revealing shared and disrupted dynamics. We demonstrate its superior performance across diverse contexts, including in pancreatitis with oncogene mutation, acute myeloid leukemia, and gastric cancer.<\/jats:p>","DOI":"10.1101\/2023.11.11.566719","type":"posted-content","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T14:15:18Z","timestamp":1700057718000},"source":"Crossref","is-referenced-by-count":8,"title":["Joint representation and visualization of derailed cell states with Decipher"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5428-9810","authenticated-orcid":false,"given":"Achille","family":"Nazaret","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9361-9333","authenticated-orcid":false,"given":"Joy Linyue","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent-Philippe","family":"Lavall\u00e9e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Burdziak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E.","family":"Cornish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaidotas","family":"Kiseliovas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Bowman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignas","family":"Masilionis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyoung","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira E.","family":"Eisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingting","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross L.","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linas","family":"Mazutis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Blei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Pe\u2019er","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5059-6971","authenticated-orcid":false,"given":"Elham","family":"Azizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024110820100814000_2023.11.11.566719v2.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"2024110820100814000_2023.11.11.566719v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.060"},{"key":"2024110820100814000_2023.11.11.566719v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0195-y"},{"key":"2024110820100814000_2023.11.11.566719v2.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0236-7"},{"key":"2024110820100814000_2023.11.11.566719v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.047"},{"key":"2024110820100814000_2023.11.11.566719v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00784-1"},{"key":"2024110820100814000_2023.11.11.566719v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.029"},{"key":"2024110820100814000_2023.11.11.566719v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0944-y"},{"key":"2024110820100814000_2023.11.11.566719v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03569-1"},{"key":"2024110820100814000_2023.11.11.566719v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01227-z"},{"key":"2024110820100814000_2023.11.11.566719v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01346-6"},{"key":"2024110820100814000_2023.11.11.566719v2.12","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4772-0"},{"key":"2024110820100814000_2023.11.11.566719v2.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0071-9"},{"key":"2024110820100814000_2023.11.11.566719v2.14","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv325"},{"key":"2024110820100814000_2023.11.11.566719v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.005"},{"key":"2024110820100814000_2023.11.11.566719v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2415"},{"key":"2024110820100814000_2023.11.11.566719v2.17","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.13"},{"key":"2024110820100814000_2023.11.11.566719v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.05.015"},{"key":"2024110820100814000_2023.11.11.566719v2.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.02.006"},{"key":"2024110820100814000_2023.11.11.566719v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.031"},{"key":"2024110820100814000_2023.11.11.566719v2.21","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-018-0317-6"},{"key":"2024110820100814000_2023.11.11.566719v2.22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516192"},{"key":"2024110820100814000_2023.11.11.566719v2.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2864-x"},{"key":"2024110820100814000_2023.11.11.566719v2.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301689"},{"key":"2024110820100814000_2023.11.11.566719v2.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.01.011"},{"key":"2024110820100814000_2023.11.11.566719v2.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19012-4"},{"key":"2024110820100814000_2023.11.11.566719v2.27","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.31.551097"},{"key":"2024110820100814000_2023.11.11.566719v2.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01337-5"},{"key":"2024110820100814000_2023.11.11.566719v2.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109992"},{"key":"2024110820100814000_2023.11.11.566719v2.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0113-3"},{"key":"2024110820100814000_2023.11.11.566719v2.31","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"2024110820100814000_2023.11.11.566719v2.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-00895-7"},{"key":"2024110820100814000_2023.11.11.566719v2.33","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4091"},{"key":"2024110820100814000_2023.11.11.566719v2.34","doi-asserted-by":"publisher","DOI":"10.1101\/460147"},{"key":"2024110820100814000_2023.11.11.566719v2.35","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02015-1"},{"key":"2024110820100814000_2023.11.11.566719v2.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0391-8"},{"key":"2024110820100814000_2023.11.11.566719v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0229-21"},{"key":"2024110820100814000_2023.11.11.566719v2.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01716-9"},{"key":"2024110820100814000_2023.11.11.566719v2.39","doi-asserted-by":"crossref","first-page":"qaa052","DOI":"10.1093\/nargab\/lqaa052","article-title":"Comparison of visualization tools for single-cell RNAseq data","volume":"2","year":"2020","journal-title":"NAR Genom Bioinform"},{"key":"2024110820100814000_2023.11.11.566719v2.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098679"},{"key":"2024110820100814000_2023.11.11.566719v2.41","doi-asserted-by":"publisher","DOI":"10.1101\/2021.08.25.457696"},{"key":"2024110820100814000_2023.11.11.566719v2.42","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01050-x"},{"key":"2024110820100814000_2023.11.11.566719v2.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01001-7"},{"key":"2024110820100814000_2023.11.11.566719v2.44","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa169"},{"key":"2024110820100814000_2023.11.11.566719v2.45","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1411.2581"},{"key":"2024110820100814000_2023.11.11.566719v2.46","unstructured":"Ferreira PF , Kuipers J , Beerenwinkel N. Deep exponential families for single-cell data analysis [Internet]. bioRxiv. 2022 [cited 2024 Oct 25]. p. 2022.10.15.512383. Available from: https:\/\/www.biorxiv.org\/content\/10.1101\/2022.10.15.512383v2.abstract"},{"key":"2024110820100814000_2023.11.11.566719v2.47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1011288"},{"key":"2024110820100814000_2023.11.11.566719v2.48","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4314"},{"key":"2024110820100814000_2023.11.11.566719v2.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01186-x"},{"key":"2024110820100814000_2023.11.11.566719v2.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02302-w"},{"key":"2024110820100814000_2023.11.11.566719v2.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25773-3"},{"key":"2024110820100814000_2023.11.11.566719v2.52","doi-asserted-by":"publisher","DOI":"10.1126\/science.add5327"},{"key":"2024110820100814000_2023.11.11.566719v2.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03147-x"},{"key":"2024110820100814000_2023.11.11.566719v2.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.10.025"},{"key":"2024110820100814000_2023.11.11.566719v2.55","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.09.009"},{"key":"2024110820100814000_2023.11.11.566719v2.56","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.502"},{"key":"2024110820100814000_2023.11.11.566719v2.57","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004226"},{"key":"2024110820100814000_2023.11.11.566719v2.58","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2413"},{"key":"2024110820100814000_2023.11.11.566719v2.59","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax5863"},{"key":"2024110820100814000_2023.11.11.566719v2.60","doi-asserted-by":"publisher","DOI":"10.1038\/nature13038"},{"key":"2024110820100814000_2023.11.11.566719v2.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01480-1"},{"key":"2024110820100814000_2023.11.11.566719v2.62","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-06760-1"},{"key":"2024110820100814000_2023.11.11.566719v2.63","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11591-1"},{"key":"2024110820100814000_2023.11.11.566719v2.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.01.004"},{"key":"2024110820100814000_2023.11.11.566719v2.65","first-page":"2579","article-title":"Visualizing Data using t-SNE","volume":"9","year":"2008","journal-title":"Journal of Machine Learning Research"},{"key":"2024110820100814000_2023.11.11.566719v2.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"2024110820100814000_2023.11.11.566719v2.67","doi-asserted-by":"publisher","DOI":"10.1038\/nature24294"},{"key":"2024110820100814000_2023.11.11.566719v2.68","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-21-1146"},{"key":"2024110820100814000_2023.11.11.566719v2.69","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3594"},{"key":"2024110820100814000_2023.11.11.566719v2.70","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01593-2"},{"key":"2024110820100814000_2023.11.11.566719v2.71","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.174"},{"key":"2024110820100814000_2023.11.11.566719v2.72","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-760595"},{"key":"2024110820100814000_2023.11.11.566719v2.73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222491799"},{"key":"2024110820100814000_2023.11.11.566719v2.74","unstructured":"Nazaret, Fan , Pe\u2019er, Azizi . Probabilistic basis decomposition for characterizing temporal dynamics of gene expression. ICML Workshop on Computational Biology [Internet]. 2022. Available from: https:\/\/icml-compbio.github.io\/2022\/papers\/WCBICML2022_paper_33.pdf"},{"key":"2024110820100814000_2023.11.11.566719v2.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05812-3"},{"key":"2024110820100814000_2023.11.11.566719v2.76","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604"},{"key":"2024110820100814000_2023.11.11.566719v2.77","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105381"},{"key":"2024110820100814000_2023.11.11.566719v2.78","doi-asserted-by":"publisher","DOI":"10.3390\/biom12101359"},{"key":"2024110820100814000_2023.11.11.566719v2.79","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3610"},{"key":"2024110820100814000_2023.11.11.566719v2.80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212127"},{"key":"2024110820100814000_2023.11.11.566719v2.81","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.009"},{"key":"2024110820100814000_2023.11.11.566719v2.82","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00251-1"},{"key":"2024110820100814000_2023.11.11.566719v2.83","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"2024110820100814000_2023.11.11.566719v2.84","unstructured":"Hoffman MD , Blei DM , Wang C , Paisley J. Stochastic variational inference. J Mach Learn Res."},{"key":"2024110820100814000_2023.11.11.566719v2.85","unstructured":"Lalchand V , Ravuri A , Lawrence ND . Generalised GPLVM with Stochastic Variational Inference. International Conference on Artificial Intelligence and Statistics. PMLR; 2022. p. 7841\u201364."},{"key":"2024110820100814000_2023.11.11.566719v2.86","first-page":"1783","article-title":"Probabilistic Non-linear Principal Component Analysis with Gaussian Process Latent Variable Models","volume":"6","year":"2005","journal-title":"J Mach Learn Res"},{"key":"2024110820100814000_2023.11.11.566719v2.87","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20020453"},{"key":"2024110820100814000_2023.11.11.566719v2.88","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01635-4"},{"key":"2024110820100814000_2023.11.11.566719v2.89","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.12.5002.5002_5002_5012"},{"key":"2024110820100814000_2023.11.11.566719v2.90","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001742"},{"key":"2024110820100814000_2023.11.11.566719v2.91","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/ac0b7e"},{"key":"2024110820100814000_2023.11.11.566719v2.92","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.08.005"},{"key":"2024110820100814000_2023.11.11.566719v2.93","first-page":"27","article-title":"An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia","volume":"4","year":"2023","journal-title":"Nat Cancer"},{"key":"2024110820100814000_2023.11.11.566719v2.94","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12952"},{"key":"2024110820100814000_2023.11.11.566719v2.95","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2018.08.004"},{"key":"2024110820100814000_2023.11.11.566719v2.96","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.018"},{"key":"2024110820100814000_2023.11.11.566719v2.97","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202154262"},{"key":"2024110820100814000_2023.11.11.566719v2.98","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-03-784116"},{"key":"2024110820100814000_2023.11.11.566719v2.99","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01613-1"},{"key":"2024110820100814000_2023.11.11.566719v2.100","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.42.6.567"},{"key":"2024110820100814000_2023.11.11.566719v2.101","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0237"},{"key":"2024110820100814000_2023.11.11.566719v2.102","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00790-6"},{"key":"2024110820100814000_2023.11.11.566719v2.103","first-page":"2825","article-title":"Scikit-learn: Machine learning in Python","volume":"12","year":"2011","journal-title":"the Journal of machine Learning research"},{"key":"2024110820100814000_2023.11.11.566719v2.104","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0686-2"},{"key":"2024110820100814000_2023.11.11.566719v2.105","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4401"},{"key":"2024110820100814000_2023.11.11.566719v2.106","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh012"},{"key":"2024110820100814000_2023.11.11.566719v2.107","doi-asserted-by":"crossref","unstructured":"Alonso-Curbelo, D. , Ho, Y.-J. , Burdziak, C. , Maag, J. L. , Morris IV, J. P. , Chandwani, R. , Chen, H.-A. , Tsanov, K. M. , Barriga, F. M. , Luan, W. , et al. A gene\u2013environment-induced epigenetic program initiates tumorigenesis. Nature (2021).","DOI":"10.1038\/s41586-020-03147-x"},{"key":"2024110820100814000_2023.11.11.566719v2.108","doi-asserted-by":"crossref","unstructured":"Azizi, E. , Carr, A. J. , Plitas, G. , Cornish, A. E. , Konopacki, C. , Prabhakaran, S. , Nainys, J. , Wu, K. , Kiseliovas, V. , Setty, M. , et al. Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell (2018).","DOI":"10.1101\/221994"},{"key":"2024110820100814000_2023.11.11.566719v2.109","unstructured":"Bingham, E. , Chen, J. P. , Jankowiak, M. , Obermeyer, F. , Pradhan, N. , Karaletsos, T. , Singh, R. , Szerlip, P. , Hors-fall, P. & Goodman, N. D. Pyro: deep universal probabilistic programming. The Journal of Machine Learning Research (2019)."},{"key":"2024110820100814000_2023.11.11.566719v2.110","doi-asserted-by":"crossref","unstructured":"Blei, D. M. Build, compute, critique, repeat: data analysis with latent variable models. Annual Review of Statistics and Its Application (2014).","DOI":"10.1146\/annurev-statistics-022513-115657"},{"key":"2024110820100814000_2023.11.11.566719v2.111","doi-asserted-by":"crossref","unstructured":"Blei, D. , Kucukelbir, A. & McAuliffe, J. D. Variational inference: a review for statisticians. Journal of the American Statistical Association (2017).","DOI":"10.1080\/01621459.2017.1285773"},{"key":"2024110820100814000_2023.11.11.566719v2.112","doi-asserted-by":"crossref","unstructured":"Blei, D. M. , Ng, A. Y. & Jordan, M. I. Latent dirichlet allocation. Journal of machine Learning research (2003).","DOI":"10.7551\/mitpress\/1120.003.0082"},{"key":"2024110820100814000_2023.11.11.566719v2.113","doi-asserted-by":"crossref","unstructured":"Burdziak, C. , Alonso-Curbelo, D. , Walle, T. , Reyes, J. , Barriga, F. M. , Haviv, D. , Xie, Y. , Zhao, Z. , Zhao, C. J. , Chen, H.-A. , et al. Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis. Science (2023).","DOI":"10.1126\/science.add5327"},{"key":"2024110820100814000_2023.11.11.566719v2.114","doi-asserted-by":"crossref","unstructured":"Cacchiarelli, D. , Qiu, X. , Srivatsan, S. , Manfredi, A. , Ziller, M. , Overbey, E. , Grimaldi, A. , Grimsby, J. , Pokharel, P. , Livak, K. J. , et al. Aligning single-cell developmental and reprogramming trajectories identifies molecular determinants of myogenic reprogramming outcome. Cell Systems (2018).","DOI":"10.1101\/122531"},{"key":"2024110820100814000_2023.11.11.566719v2.115","doi-asserted-by":"crossref","unstructured":"Chari, T. & Pachter, L. The specious art of single-cell genomics. PLOS Computational Biology (2023).","DOI":"10.1371\/journal.pcbi.1011288"},{"key":"2024110820100814000_2023.11.11.566719v2.116","doi-asserted-by":"crossref","unstructured":"Danecek, P. , Bonfield, J. K. , Liddle, J. , Marshall, J. , Ohan, V. , Pollard, M. O. , Whitwham, A. , Keane, T. , Mc-Carthy, S. A. , Davies, R. M. & Li, H. Twelve years of SAMtools and BCFtools. GigaScience. giab008 (2021).","DOI":"10.1093\/gigascience\/giab008"},{"key":"2024110820100814000_2023.11.11.566719v2.117","doi-asserted-by":"crossref","unstructured":"Fischer, M. Census and evaluation of p53 target genes. Oncogene (2017).","DOI":"10.1038\/onc.2016.502"},{"key":"2024110820100814000_2023.11.11.566719v2.118","doi-asserted-by":"crossref","unstructured":"Gayoso, A. , Lopez, R. , Xing, G. , Boyeau, P. , Valiollah Pour Amiri, V. , Hong, J. , Wu, K. , Jayasuriya, M. , Mehlman, E. , Langevin, M. , Liu, Y. , Samaran, J. , Misrachi, G. , Nazaret, A. , Clivio, O. , et al. A python library for probabilistic analysis of single-cell omics data. Nature biotechnology (2022).","DOI":"10.1038\/s41587-021-01206-w"},{"key":"2024110820100814000_2023.11.11.566719v2.119","unstructured":"Gayoso, A. , Shor, J. , Carr, A. J. , Sharma, R. & Pe\u2019er, D. Doubletdetection (version v2. 4). Zenodo, DOI (2018)."},{"key":"2024110820100814000_2023.11.11.566719v2.120","unstructured":"Higgins, I. , Matthey, L. , Pal, A. , Burgess, C. , Glorot, X. , Botvinick, M. , Mohamed, S. & Lerchner, A. Beta-vae: learning basic visual concepts with a constrained variational framework in International conference on learning representations (2016)."},{"key":"2024110820100814000_2023.11.11.566719v2.121","unstructured":"Hoffman, M. D. , Blei, D. M. , Wang, C. & Paisley, J. Stochastic variational inference. Journal of Machine Learning Research (2013)."},{"key":"2024110820100814000_2023.11.11.566719v2.122","doi-asserted-by":"crossref","unstructured":"Hunter, J. D. Matplotlib: a 2d graphics environment. Computing in Science & Engineering (2007).","DOI":"10.1109\/MCSE.2007.55"},{"key":"2024110820100814000_2023.11.11.566719v2.123","doi-asserted-by":"crossref","unstructured":"Jordan, M. I. , Ghahramani, Z. , Jaakkola, T. S. & Saul, L. K. An introduction to variational methods for graphical models. Machine Learning (1999).","DOI":"10.1007\/978-94-011-5014-9_5"},{"key":"2024110820100814000_2023.11.11.566719v2.124","doi-asserted-by":"crossref","unstructured":"Kanton, S. , Boyle, M. J. , He, Z. , Santel, M. , Weigert, A. , Sanch\u00eds-Calleja, F. , Guijarro, P. , Sidow, L. , Fleck, J. S. , Han, D. , et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature (2019).","DOI":"10.1101\/685057"},{"key":"2024110820100814000_2023.11.11.566719v2.125","doi-asserted-by":"crossref","unstructured":"Kim, J. , Park, C. , Kim, K. H. , Kim, E. H. , Kim, H. , Woo, J. K. , Seong, J. K. , Nam, K. T. , Lee, Y. C. & Cho, S. Y. Single-cell analysis of gastric pre-cancerous and cancer lesions reveals cell lineage diversity and intratumoral heterogeneity. NPJ Precision Oncology (2022).","DOI":"10.1038\/s41698-022-00251-1"},{"key":"2024110820100814000_2023.11.11.566719v2.126","unstructured":"Kingma, D. P. & Ba, J. Adam: a method for stochastic optimization. arXiv preprint arXiv:1412.6980 (2014)."},{"key":"2024110820100814000_2023.11.11.566719v2.127","unstructured":"Kingma, D. P. & Welling, M. Auto-encoding variational bayes. arXiv preprint arXiv:1312.6114 (2013)."},{"key":"2024110820100814000_2023.11.11.566719v2.128","doi-asserted-by":"crossref","unstructured":"Levine, J. H. , Simonds, E. F. , Bendall, S. C. , Davis, K. L. , ad D. Amir, E. , Tadmor, M. D. , Litvin, O. , Fien-berg, H. G. , Jager, A. , Zunder, E. R. , Finck, R. , Gedman, A. L. , Radtke, I. , Downing, J. R. , Pe\u2019er, D. & Nolan, G. P. Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Cell (2015).","DOI":"10.1016\/j.cell.2015.05.047"},{"key":"2024110820100814000_2023.11.11.566719v2.129","doi-asserted-by":"crossref","unstructured":"Levitin, H. M. , Yuan, J. , Cheng, Y. L. , Ruiz, F. J. , Bush, E. C. , Bruce, J. N. , Canoll, P. , Iavarone, A. , Lasorella, A. , Blei, D. M. , et al. De novo gene signature identification from single-cell rna-seq with hierarchical poisson factorization. Molecular systems biology (2019).","DOI":"10.1101\/367003"},{"key":"2024110820100814000_2023.11.11.566719v2.130","unstructured":"Lopez, R. , Nazaret, A. , Langevin, M. , Samaran, J. , Regier, J. , Jordan, M. I. & Yosef, N. A joint model of un-paired data from scrna-seq and spatial transcriptomics for imputing missing gene expression measurements. arXiv preprint arXiv:1905.02269 (2019)."},{"key":"2024110820100814000_2023.11.11.566719v2.131","doi-asserted-by":"crossref","unstructured":"Lopez, R. , Regier, J. , Cole, M. B. , Jordan, M. I. & Yosef, N. Deep generative modeling for single-cell transcriptomics. Nature methods (2018).","DOI":"10.1038\/s41592-018-0229-2"},{"key":"2024110820100814000_2023.11.11.566719v2.132","doi-asserted-by":"crossref","unstructured":"Love, M. I. , Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for rna-seq data with deseq2. Genome biology (2014).","DOI":"10.1101\/002832"},{"key":"2024110820100814000_2023.11.11.566719v2.133","doi-asserted-by":"crossref","unstructured":"McDowell, I. C. , Manandhar, D. , Vockley, C. M. , Schmid, A. K. , Reddy, T. E. & Engelhardt, B. E. Clustering gene expression time series data using an infinite gaussian process mixture model. PLoS computational biology (2018).","DOI":"10.1101\/131151"},{"key":"2024110820100814000_2023.11.11.566719v2.134","doi-asserted-by":"crossref","unstructured":"Neal, R. M. in Bayesian Learning for Neural Networks (1996).","DOI":"10.1007\/978-1-4612-0745-0"},{"key":"2024110820100814000_2023.11.11.566719v2.135","doi-asserted-by":"crossref","unstructured":"Novershtern, N. , Subramanian, A. , Lawton, L. N. , Mak, R. H. , Haining, W. N. , McConkey, M. E. , Habib, N. , Yosef, N. , Chang, C. Y. , Shay, T. , et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell (2011).","DOI":"10.1016\/j.cell.2011.01.004"},{"key":"2024110820100814000_2023.11.11.566719v2.136","unstructured":"Pedregosa, F. , Varoquaux, G. , Gramfort, A. , Michel, V. , Thirion, B. , Grisel, O. , Blondel, M. , Prettenhofer, P. , Weiss, R. , Dubourg, V. , Vanderplas, J. , Passos, A. , Cournapeau, D. , Brucher, M. , Perrot, M. & Duchesnay, E. Scikit-learn: machine learning in Python. Journal of Machine Learning Research (2011)."},{"key":"2024110820100814000_2023.11.11.566719v2.137","doi-asserted-by":"crossref","unstructured":"Risso, D. , Perraudeau, F. , Gribkova, S. , Dudoit, S. & Vert, J.-P. A general and flexible method for signal extraction from single-cell rna-seq data. Nature communications (2018).","DOI":"10.1101\/125112"},{"key":"2024110820100814000_2023.11.11.566719v2.138","doi-asserted-by":"crossref","unstructured":"Robinson, J. T. , Thorvaldsd\u00f3ttir, H. , Winckler, W. , Guttman, M. , Lander, E. S. , Getz, G. & Mesirov, J. P. Integrative genomics viewer. Nature biotechnology (2011).","DOI":"10.1038\/nbt.1754"},{"key":"2024110820100814000_2023.11.11.566719v2.139","doi-asserted-by":"crossref","unstructured":"Satpathy, A. T. , Granja, J. M. , Yost, K. E. , Qi, Y. , Meschi, F. , McDermott, G. P. , Olsen, B. N. , Mumbach, M. R. , Pierce, S. E. , Corces, M. R. , et al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral t cell exhaustion. Nature biotechnology (2019).","DOI":"10.1101\/610550"},{"key":"2024110820100814000_2023.11.11.566719v2.140","doi-asserted-by":"crossref","unstructured":"Setty, M. , Tadmor, M. D. , Reich-Zeliger, S. , Angel, O. , Salame, T. M. , Kathail, P. , Choi, K. , Bendall, S. , Friedman, N. & Pe\u2019er, D. Wishbone identifies bifurcating developmental trajectories from single-cell data. Nature biotechnology (2016).","DOI":"10.1038\/nbt.3569"},{"key":"2024110820100814000_2023.11.11.566719v2.141","doi-asserted-by":"crossref","unstructured":"Shi, J. & Walker, M. G. Gene set enrichment analysis (gsea) for interpreting gene expression profiles. Current Bioinformatics (2007).","DOI":"10.2174\/157489307780618231"},{"key":"2024110820100814000_2023.11.11.566719v2.142","doi-asserted-by":"crossref","unstructured":"Svensson, V. , Gayoso, A. , Yosef, N. & Pachter, L. Interpretable factor models of single-cell rna-seq via variational autoencoders. Bioinformatics (2020).","DOI":"10.1101\/737601"},{"key":"2024110820100814000_2023.11.11.566719v2.143","doi-asserted-by":"crossref","unstructured":"Traag, V. A. , Waltman, L. & Van Eck, N. J. From louvain to leiden: guaranteeing well-connected communities. Scientific reports (2019).","DOI":"10.1038\/s41598-019-41695-z"},{"key":"2024110820100814000_2023.11.11.566719v2.144","doi-asserted-by":"crossref","unstructured":"Trapnell, C. , Cacchiarelli, D. , Grimsby, J. , Pokharel, P. , Li, S. , Morse, M. , Lennon, N. J. , Livak, K. J. , Mikkelsen, T. S. & Rinn, J. L. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nature biotechnology (2014).","DOI":"10.1038\/nbt.2859"},{"key":"2024110820100814000_2023.11.11.566719v2.145","doi-asserted-by":"crossref","unstructured":"Van den Berge, K. , Roux de B\u00e9zieux, H. , Street, K. , Saelens, W. , Cannoodt, R. , Saeys, Y. , Dudoit, S. & Clement, L. Trajectory-based differential expression analysis for single-cell sequencing data. Nature communications (2020).","DOI":"10.1101\/623397"},{"key":"2024110820100814000_2023.11.11.566719v2.146","unstructured":"Virtanen, P. , Gommers, R. , Oliphant, T. E. , Haberland, M. , Reddy, T. , Cournapeau, D. , Burovski, E. , Peterson, P. , Weckesser, W. , Bright, J. , et al. Scipy 1.0: fundamental algorithms for scientific computing in python. Nature methods (2020)."},{"key":"2024110820100814000_2023.11.11.566719v2.147","doi-asserted-by":"crossref","unstructured":"Wainwright, M. J. & Jordan, M. I. Graphical Models, Exponential Families, and Variational Inference (2008).","DOI":"10.1561\/9781601981851"},{"key":"2024110820100814000_2023.11.11.566719v2.148","doi-asserted-by":"crossref","unstructured":"Waskom, M. L. Seaborn: statistical data visualization. Journal of Open Source Software (2021).","DOI":"10.21105\/joss.03021"},{"key":"2024110820100814000_2023.11.11.566719v2.149","doi-asserted-by":"crossref","unstructured":"Wolf, F. A. , Angerer, P. & Theis, F. J. Scanpy: large-scale single-cell gene expression data analysis. Genome biology (2018).","DOI":"10.1101\/174029"},{"key":"2024110820100814000_2023.11.11.566719v2.150","doi-asserted-by":"crossref","unstructured":"Zheng, G. X. , Terry, J. M. , Belgrader, P. , Ryvkin, P. , Bent, Z. W. , Wilson, R. , Ziraldo, S. B. , Wheeler, T. D. , McDermott, G. P. , Zhu, J. , et al. Massively parallel digital transcriptional profiling of single cells. Nature communications (2017).","DOI":"10.1038\/ncomms14049"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.11.11.566719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:31:21Z","timestamp":1768455081000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.11.11.566719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":150,"URL":"https:\/\/doi.org\/10.1101\/2023.11.11.566719","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1186\/s13059-025-03682-8","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,11,15]]},"subtype":"preprint"}}