{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T05:52:23Z","timestamp":1762062743833,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T00:00:00Z","timestamp":1660348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council (EPSRC)","doi-asserted-by":"publisher","award":["EP\/R018472\/1","EP\/R005125\/1","EP\/T001968\/1","RGFnEAn201074\/UF150238"],"award-info":[{"award-number":["EP\/R018472\/1","EP\/R005125\/1","EP\/T001968\/1","RGFnEAn201074\/UF150238"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Royal Society","award":["EP\/R018472\/1","EP\/R005125\/1","EP\/T001968\/1","RGFnEAn201074\/UF150238"],"award-info":[{"award-number":["EP\/R018472\/1","EP\/R005125\/1","EP\/T001968\/1","RGFnEAn201074\/UF150238"]}]},{"name":"Emerson Collective","award":["EP\/R018472\/1","EP\/R005125\/1","EP\/T001968\/1","RGFnEAn201074\/UF150238"],"award-info":[{"award-number":["EP\/R018472\/1","EP\/R005125\/1","EP\/T001968\/1","RGFnEAn201074\/UF150238"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Entropy"],"abstract":"<jats:p>Analysis of single-cell transcriptomics often relies on clustering cells and then performing differential gene expression (DGE) to identify genes that vary between these clusters. These discrete analyses successfully determine cell types and markers; however, continuous variation within and between cell types may not be detected. We propose three topologically motivated mathematical methods for unsupervised feature selection that consider discrete and continuous transcriptional patterns on an equal footing across multiple scales simultaneously. Eigenscores (eigi) rank signals or genes based on their correspondence to low-frequency intrinsic patterning in the data using the spectral decomposition of the Laplacian graph. The multiscale Laplacian score (MLS) is an unsupervised method for locating relevant scales in data and selecting the genes that are coherently expressed at these respective scales. The persistent Rayleigh quotient (PRQ) takes data equipped with a filtration, allowing the separation of genes with different roles in a bifurcation process (e.g., pseudo-time). We demonstrate the utility of these techniques by applying them to published single-cell transcriptomics data sets. The methods validate previously identified genes and detect additional biologically meaningful genes with coherent expression patterns. By studying the interaction between gene signals and the geometry of the underlying space, the three methods give multidimensional rankings of the genes and visualisation of relationships between them.<\/jats:p>","DOI":"10.3390\/e24081116","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T01:47:21Z","timestamp":1660528041000},"page":"1116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multiscale Methods for Signal Selection in Single-Cell Data"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-6648","authenticated-orcid":false,"given":"Renee S.","family":"Hoekzema","sequence":"first","affiliation":[{"name":"Mathematical Institute, University of Oxford, Oxford OX1 2JD, UK"},{"name":"Department of Mathematics, Free University of Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lewis","family":"Marsh","sequence":"additional","affiliation":[{"name":"Mathematical Institute, University of Oxford, Oxford OX1 2JD, UK"},{"name":"Ludwig Institute for Cancer Research, University of Oxford, Oxford OX1 2JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-0595","authenticated-orcid":false,"given":"Otto","family":"Sumray","sequence":"additional","affiliation":[{"name":"Mathematical Institute, University of Oxford, Oxford OX1 2JD, UK"},{"name":"Ludwig Institute for Cancer Research, University of Oxford, Oxford OX1 2JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-2385","authenticated-orcid":false,"given":"Thomas M.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research, University of Oxford, Oxford OX1 2JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Lu","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research, University of Oxford, Oxford OX1 2JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen M.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Mathematical Institute, University of Oxford, Oxford OX1 2JD, UK"},{"name":"Ludwig Institute for Cancer Research, University of Oxford, Oxford OX1 2JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Mathematical Institute, University of Oxford, Oxford OX1 2JD, UK"},{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: Large-scale single-cell gene expression data analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"861","DOI":"10.21105\/joss.00861","article-title":"UMAP: Uniform Manifold Approximation and Projection","volume":"3","author":"McInnes","year":"2018","journal-title":"J. Open Source Softw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nbt.4314","article-title":"Dimensionality reduction for visualizing single-cell data using UMAP","volume":"37","author":"Becht","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_5","unstructured":"Jeitziner, R., Carri\u00e8re, M., Rougemont, J., Oudot, S., Hess, K., and Brisken, C. (2017). Two-tier mapper: A user-independent clustering method for global gene expression analysis based on topology. arXiv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nbt.3854","article-title":"Single-Cell Topological RNA-Seq Analysis Reveals Insights into Cellular Differentiation and Development","volume":"35","author":"Rizvi","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_7","unstructured":"Kuchroo, M., DiStasio, M., Calapkulu, E., Ige, M., Zhang, L., Sheth, A.H., Menon, M., Xing, Y., Gigante, S., and Huang, J. (2012). Topological Analysis of Single-Cell Data Reveals Shared Glial Landscape of Macular Degeneration and Neurodegenerative Diseases. bioRxiv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.patrec.2021.03.035","article-title":"Stable Topological Signatures for Metric Trees through Graph Approximations","volume":"147","author":"Vandaele","year":"2021","journal-title":"Pattern Recog. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1109\/JPROC.2018.2820126","article-title":"Graph signal processing: Overview, challenges, and applications","volume":"106","author":"Ortega","year":"2018","journal-title":"Proc. IEEE"},{"key":"ref_10","unstructured":"Chung, F.R. (1997). Spectral Graph Theory, American Mathematical Soc.. Number 92."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Robinson, M. (2014). Topological Signal Processing, Springer.","DOI":"10.1007\/978-3-642-36104-3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108149","DOI":"10.1016\/j.sigpro.2021.108149","article-title":"Signal processing on higher-order networks: Livin\u2019on the edge... and beyond","volume":"187","author":"Schaub","year":"2021","journal-title":"Signal Process."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1109\/TSP.2020.2981920","article-title":"Topological signal processing over simplicial complexes","volume":"68","author":"Barbarossa","year":"2020","journal-title":"IEEE Trans. Signal Process."},{"key":"ref_14","first-page":"1","article-title":"Laplacian score for feature selection","volume":"18","author":"He","year":"2005","journal-title":"Adv. Neural Inf. Process. Syst."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Govek, K.W., Yamajala, V.S., and Camara, P.G. (2019). Clustering-Independent Analysis of Genomic Data Using Spectral Simplicial Theory. PLoS Comput. Biol., 15.","DOI":"10.1371\/journal.pcbi.1007509"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Delvenne, J.C., Schaub, M.T., Yaliraki, S.N., and Barahona, M. (2013). The stability of a graph partition: A dynamics-based framework for community detection. Dynamics On and Of Complex Networks, Volume 2, Springer.","DOI":"10.1007\/978-1-4614-6729-8_11"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Schaub, M.T., Delvenne, J.C., Yaliraki, S.N., and Barahona, M. (2012). Markov Dynamics as a Zooming Lens for MultiscaleCommunity Detection: Non Clique-Like Communitiesand the Field-of-View Limit. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032210"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1109\/TCSI.2012.2215780","article-title":"Kron Reduction of Graphs With Applications to Electrical Networks","volume":"60","author":"Dorfler","year":"2013","journal-title":"IEEE Trans. Circ. Syst. I Regul. Pap."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e3376","DOI":"10.1002\/cnm.3376","article-title":"Persistent spectral graph","volume":"36","author":"Wang","year":"2020","journal-title":"Int. J. Numer. Methods Biomed. Eng."},{"key":"ref_20","unstructured":"M\u00e9moli, F., Wan, Z., and Wang, Y. (2021). Persistent Laplacians: Properties, Algorithms and Implications. arXiv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1162\/089976603321780317","article-title":"Laplacian eigenmaps for dimensionality reduction and data representation","volume":"15","author":"Belkin","year":"2003","journal-title":"Neural Comput."},{"key":"ref_22","first-page":"21","article-title":"An implicitly restarted Lanczos method for large symmetric eigenvalue problems","volume":"2","author":"Calvetti","year":"1994","journal-title":"Electron. Trans. Numer. Anal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12755","DOI":"10.1073\/pnas.0903215107","article-title":"Stability of graph communities across time scales","volume":"107","author":"Delvenne","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1109\/TNSE.2015.2391998","article-title":"Random walks, Markov processes and the multiscale modular organization of complex networks","volume":"1","author":"Lambiotte","year":"2014","journal-title":"IEEE Trans. Netw. Sci. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.physrep.2017.07.007","article-title":"Random walks and diffusion on networks","volume":"716","author":"Masuda","year":"2017","journal-title":"Phys. Rep."},{"key":"ref_26","first-page":"1082","article-title":"Communities in networks","volume":"56","author":"Porter","year":"2009","journal-title":"Not. AMS"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"P10008","DOI":"10.1088\/1742-5468\/2008\/10\/P10008","article-title":"Fast unfolding of communities in large networks","volume":"2008","author":"Blondel","year":"2008","journal-title":"J. Stat. Mech. Theory Exp."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bacik, K.A., Schaub, M.T., Beguerisse-D\u00edaz, M., Billeh, Y.N., and Barahona, M. (2016). Flow-based network analysis of the Caenorhabditis elegans connectome. PLoS Comput. Biol., 12.","DOI":"10.1371\/journal.pcbi.1005055"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Beguerisse-Diaz, M., Vangelov, B., and Barahona, M. (2013, January 3\u20135). Finding role communities in directed networks using Role-Based Similarity, Markov Stability and the Relaxed Minimum Spanning Tree. Proceedings of the 2013 IEEE Global Conference on Signal and Information Processing, Austin, TX, USA.","DOI":"10.1109\/GlobalSIP.2013.6737046"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s41109-019-0248-7","article-title":"Graph-based data clustering via multiscale community detection","volume":"5","author":"Liu","year":"2020","journal-title":"Appl. Netw. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.jmva.2006.11.013","article-title":"Comparing clusterings\u2014An information based distance","volume":"98","year":"2007","journal-title":"J. Multivar. Anal."},{"key":"ref_32","unstructured":"Barahona, M. (2022, May 23). The Stability of a Graph Partition. Available online: https:\/\/www.ma.imperial.ac.uk\/~mpbara\/Partition_Stability\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1090\/S0273-0979-07-01191-3","article-title":"Barcodes: The persistent topology of data","volume":"45","author":"Ghrist","year":"2008","journal-title":"Bull. Am. Math. Soc."},{"key":"ref_34","unstructured":"Genomics 1 (2022, June 01). 10X Peripheral Blood Mononuclear Cells (PBMC) Data. 1 June 2022. Available online: https:\/\/cf.10xgenomics.com\/samples\/cell\/pbmc3k\/pbmc3k_filtered_gene_bc_matrices.tar.gz."},{"key":"ref_35","unstructured":"Satija Lab, N. (2022, May 23). Seurat Guided Clustering Tutorial. Available online: https:\/\/satijalab.org\/seurat\/articles\/pbmc3k_tutorial.html."},{"key":"ref_36","unstructured":"Hafemeister, C., and Satija, R. (2022, May 23). Using Sctransform in Seurat. Available online: https:\/\/satijalab.org\/seurat\/articles\/sctransform_vignette.html."},{"key":"ref_37","unstructured":"Wolf, A., Ramirez, F., and Rybakov, S. (2022, August 02). Scanpy Tutorials Preprocessing and Clustering 3k PBMCs. Available online: https:\/\/scanpy-tutorials.readthedocs.io\/en\/latest\/pbmc3k.html."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/s41591-018-0096-5","article-title":"Phenotype molding of stromal cells in the lung tumor microenvironment","volume":"24","author":"Lambrechts","year":"2018","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/hep.29353","article-title":"A Single-Cell Transcriptomic Analysis Reveals Precise Pathways and Regulatory Mechanisms Underlying Hepatoblast Differentiation","volume":"66","author":"Yang","year":"2017","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"Hafemeister","year":"2019","journal-title":"Genome Biol."},{"key":"ref_41","unstructured":"Satija Lab, NYU (2022, July 23). Differential Expression Testing. Available online: https:\/\/satijalab.org\/seurat\/articles\/de_vignette.html."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s42003-020-01364-8","article-title":"Embryonic Liver Developmental Trajectory Revealed by Single-Cell RNA Sequencing in the Foxa2eGFP Mouse","volume":"3","author":"Mu","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11019","DOI":"10.1038\/s41598-020-67513-5","article-title":"Enhancing droplet-based single-nucleus RNA-seq resolution using the semi-supervised machine learning classifier DIEM","volume":"10","author":"Alvarez","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"666935","DOI":"10.3389\/fimmu.2021.666935","article-title":"Single-cell RNA sequencing reveals tissue compartment-specific plasticity of mycosis fungoides tumor cells","volume":"12","author":"Rindler","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/hep4.1184","article-title":"Metastasis-associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune-mediated liver damage","volume":"2","author":"Sookoian","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_46","first-page":"1574","article-title":"Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway","volume":"116","author":"Cohen","year":"2010","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1182\/blood-2005-08-3364","article-title":"Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease","volume":"107","author":"Theurl","year":"2006","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3389\/fimmu.2019.00131","article-title":"Ferritin light chain confers protection against sepsis-induced inflammation and organ injury","volume":"10","author":"Zarjou","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11906","DOI":"10.1073\/pnas.1818488116","article-title":"Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRV\u03b41 and TCRV\u03b42 \u03b3\u03b4 T lymphocytes","volume":"116","author":"Pizzolato","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"885","DOI":"10.2147\/JIR.S293993","article-title":"Altered monocyte subsets in Kawasaki disease revealed by single-cell RNA-sequencing","volume":"14","author":"Geng","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.3389\/fimmu.2020.01070","article-title":"Human monocyte subset distinctions and function: Insights from gene expression analysis","volume":"11","author":"Cormican","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"565","DOI":"10.4049\/jimmunol.1701128","article-title":"Epigenetic and posttranscriptional regulation of CD16 expression during human NK cell development","volume":"200","author":"Victor","year":"2018","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/s41423-020-00574-8","article-title":"Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia","volume":"18","author":"Crinier","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrg3833","article-title":"Computational and analytical challenges in single-cell transcriptomics","volume":"16","author":"Stegle","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-27232-5","article-title":"Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation","volume":"12","author":"Lee","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"656353","DOI":"10.3389\/fmicb.2021.656353","article-title":"Antiviral activity of interferon alpha-inducible protein 27 against hepatitis B virus gene expression and replication","volume":"12","author":"Ullah","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10762","DOI":"10.1073\/pnas.1509070112","article-title":"IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin\u2013EGFR interactions","volume":"112","author":"Monticelli","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.immuni.2015.01.020","article-title":"Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair","volume":"42","author":"Zaiss","year":"2015","journal-title":"Immunity"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e55232","DOI":"10.7554\/eLife.55232","article-title":"Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+ NKG2A-NK cells","volume":"9","author":"Bennstein","year":"2020","journal-title":"Elife"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ni.2534","article-title":"Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues","volume":"14","author":"Bernink","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s41587-019-0071-9","article-title":"A Comparison of Single-Cell Trajectory Inference Methods","volume":"37","author":"Saelens","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1038\/s41467-020-14766-3","article-title":"Trajectory-Based Differential Expression Analysis for Single-Cell Sequencing Data","volume":"11","author":"Street","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The Dynamics and Regulators of Cell Fate Decisions Are Revealed by Pseudotemporal Ordering of Single Cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed Graph Embedding Resolves Complex Single-Cell Trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eaal2192","DOI":"10.1126\/sciimmunol.aal2192","article-title":"Single-Cell RNA-seq and Computational Analysis Using Temporal Mixture Modelling Resolves Th1\/Tfh Fate Bifurcation in Malaria","volume":"2","author":"Svensson","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1093\/nar\/gkw430","article-title":"TSCAN: Pseudo-time Reconstruction and Evaluation in Single-Cell RNA-seq Analysis","volume":"44","author":"Ji","year":"2016","journal-title":"Nucl. Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12864-017-4342-x","article-title":"Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver development","volume":"18","author":"Su","year":"2017","journal-title":"BMC Genom."},{"key":"ref_68","unstructured":"(2022, August 02). The Human Protein Atlas\u2014MDK. Available online: https:\/\/www.proteinatlas.org\/ENSG00000110492-MDK\/single+cell+type\/liver."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1101\/gad.1567107","article-title":"Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria","volume":"21","author":"Leu","year":"2007","journal-title":"Genes Dev."},{"key":"ref_70","first-page":"1","article-title":"Identification of relevant genetic alterations in cancer using topological data analysis","volume":"11","author":"Mohamedi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1109\/TSP.2014.2345355","article-title":"Graph wavelets for multiscale community mining","volume":"62","author":"Tremblay","year":"2014","journal-title":"IEEE Trans. Signal Process."},{"key":"ref_72","unstructured":"Bick, C., Gross, E., Harrington, H.A., and Schaub, M.T. (2021). What are higher-order networks?. arXiv."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kuchroo, M., Godavarthi, A., Tong, A., Wolf, G., and Krishnaswamy, S. (2021, January 25\u201328). Multimodal Data Visualization and Denoising with Integrated Diffusion. Proceedings of the 2021 IEEE 31st International Workshop on Machine Learning for Signal Processing (MLSP), Gold Coast, Australia.","DOI":"10.1109\/MLSP52302.2021.9596214"}],"container-title":["Entropy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1099-4300\/24\/8\/1116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:08:17Z","timestamp":1760141297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1099-4300\/24\/8\/1116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,13]]},"references-count":73,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["e24081116"],"URL":"https:\/\/doi.org\/10.3390\/e24081116","relation":{},"ISSN":["1099-4300"],"issn-type":[{"type":"electronic","value":"1099-4300"}],"subject":[],"published":{"date-parts":[[2022,8,13]]}}}