{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:34:20Z","timestamp":1784014460453,"version":"3.55.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T00:00:00Z","timestamp":1714262400000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF1202100"],"award-info":[{"award-number":["2022YFF1202100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62172087"],"award-info":[{"award-number":["62172087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62072095"],"award-info":[{"award-number":["62072095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Foundation for Distinguished Young Scholars of China","award":["62225109"],"award-info":[{"award-number":["62225109"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the growth and development of multicellular organisms, the immune processes of the immune system and the maintenance of the organism\u2019s internal environment, cell communication plays a crucial role. It exerts a significant influence on regulating internal cellular states such as gene expression and cell functionality. Currently, the mainstream methods for studying intercellular communication are focused on exploring the ligand\u2013receptor\u2013transcription factor and ligand\u2013receptor\u2013subunit scales. However, there is relatively limited research on the association between intercellular communication and highly variable genes (HVGs). As some HVGs are closely related to cell communication, accurately identifying these HVGs can enhance the accuracy of constructing cell communication networks. The rapid development of single-cell sequencing (scRNA-seq) and spatial transcriptomics technologies provides a data foundation for exploring the relationship between intercellular communication and HVGs. Therefore, we propose CPPLS-MLP, which can identify HVGs closely related to intercellular communication and further analyze the impact of Multiple Input Multiple Output cellular communication on the differential expression of these HVGs. By comparing with the commonly used method CCPLS for constructing intercellular communication networks, we validated the superior performance of our method in identifying cell-type-specific HVGs and effectively analyzing the influence of neighboring cell types on HVG expression regulation. Source codes for the CPPLS_MLP R, python packages and the related scripts are available at \u2018CPPLS_MLP Github [https:\/\/github.com\/wuzhenao\/CPPLS-MLP]\u2019.<\/jats:p>","DOI":"10.1093\/bib\/bbae198","type":"journal-article","created":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T08:49:33Z","timestamp":1714294173000},"source":"Crossref","is-referenced-by-count":8,"title":["CPPLS-MLP: a method for constructing cell\u2013cell communication networks and identifying related highly variable genes based on single-cell sequencing and spatial transcriptomics data"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9807-8620","authenticated-orcid":false,"given":"Tianjiao","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University Harbin , 150040 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3774-8660","authenticated-orcid":false,"given":"Zhenao","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University Harbin , 150040 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0594-5625","authenticated-orcid":false,"given":"Liangyu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University Harbin , 150040 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3584-6125","authenticated-orcid":false,"given":"Jixiang","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University Harbin , 150040 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0887-9795","authenticated-orcid":false,"given":"Ziheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University Harbin , 150040 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University Harbin , 150040 , China"},{"name":"Faculty of Computing, Harbin Institute of Technology Harbin , 150001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"2024042808492200400_ref1","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1007\/s13238-020-00727-5","article-title":"New avenues for systematically inferring cell-cell communication: through single-cell transcriptomics data","volume":"11","author":"Shao","year":"2020","journal-title":"Protein Cell"},{"key":"2024042808492200400_ref2","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41580-023-00615-w","article-title":"The technological landscape and applications of single-cell multi-omics","volume":"24","author":"Baysoy","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024042808492200400_ref3","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.molcel.2019.12.012","article-title":"PD-1 imposes qualitative control of cellular transcriptomes in response to T cell activation","volume":"77","author":"Shimizu","year":"2020","journal-title":"Mol Cell"},{"key":"2024042808492200400_ref4","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1126\/science.1222161","article-title":"Using cell-to-cell variability\u2014a new era in molecular biology","volume":"336","author":"Pelkmans","year":"2012","journal-title":"Science"},{"key":"2024042808492200400_ref5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nri.2017.108","article-title":"The diverse functions of the PD1 inhibitory pathway","volume":"18","author":"Sharpe","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"2024042808492200400_ref6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nrm3044","article-title":"Origins of regulated cell-to-cell variability","volume":"12","author":"Snijder","year":"2011","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024042808492200400_ref7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","article-title":"NicheNet: modeling intercellular communication by linking ligands to target genes","volume":"17","author":"Browaeys","year":"2020","journal-title":"Nat Methods"},{"key":"2024042808492200400_ref8","first-page":"eabf1356","article-title":"CytoTalk: De novo construction of signal transduction networks using single-cell transcriptomic data, science","volume":"7","author":"Hu","year":"2021","journal-title":"Advances"},{"key":"2024042808492200400_ref9","doi-asserted-by":"crossref","first-page":"8520","DOI":"10.1093\/nar\/gkab638","article-title":"CellCall: integrating paired ligand\u2013receptor and transcription factor activities for cell\u2013cell communication","volume":"49","author":"Zhang","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2024042808492200400_ref10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s42003-021-02986-2","article-title":"InterCellar enables interactive analysis and exploration of cell\u2212 cell communication in single-cell transcriptomic data","volume":"5","author":"Interlandi","year":"2022","journal-title":"Communications biology"},{"key":"2024042808492200400_ref11","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1093\/nar\/gkaa183","article-title":"SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics","volume":"48","author":"Cabello-Aguilar","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2024042808492200400_ref12","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","article-title":"CellPhoneDB: inferring cell\u2013cell communication from combined expression of multi-subunit ligand\u2013receptor complexes","volume":"15","author":"Efremova","year":"2020","journal-title":"Nat Protoc"},{"key":"2024042808492200400_ref13","doi-asserted-by":"crossref","first-page":"bbaa283","DOI":"10.1093\/bib\/bbaa283","article-title":"FunRes: resolving tissue-specific functional cell states based on a cell\u2013cell communication network model","volume":"22","author":"Jung","year":"2021","journal-title":"Brief Bioinform"},{"key":"2024042808492200400_ref14","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"2024042808492200400_ref15","doi-asserted-by":"crossref","first-page":"bbac234","DOI":"10.1093\/bib\/bbac234","article-title":"Cell\u2013cell communication inference and analysis in the tumour microenvironments from single-cell transcriptomics: data resources and computational strategies","volume":"23","author":"Peng","year":"2022","journal-title":"Brief Bioinform"},{"key":"2024042808492200400_ref16","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.3390\/cancers15072057","article-title":"The matrix reloaded\u2014the role of the extracellular matrix in cancer","volume":"15","author":"Raskov","year":"2023","journal-title":"Cancer"},{"key":"2024042808492200400_ref17","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev-immunol-100219-020937","article-title":"Regulatory T cell development","volume":"38","author":"Savage","year":"2020","journal-title":"Annu Rev Immunol"},{"key":"2024042808492200400_ref18","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1093\/bioinformatics\/btaa482","article-title":"COMUNET: a tool to explore and visualize intercellular communication","volume":"36","author":"Solovey","year":"2020","journal-title":"Bioinformatics"},{"key":"2024042808492200400_ref19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/cells9010014","article-title":"Single-cell expression variability implies cell function","volume":"9","author":"Osorio","year":"2020","journal-title":"Cells"},{"key":"2024042808492200400_ref20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41576-020-00292-x","article-title":"Deciphering cell\u2013cell interactions and communication from gene expression","volume":"22","author":"Armingol","year":"2021","journal-title":"Nat Rev Genet"},{"key":"2024042808492200400_ref21","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1038\/s41467-020-18873-z","article-title":"Predicting cell-to-cell communication networks using NATMI","volume":"11","author":"Hou","year":"2020","journal-title":"Nat Commun"},{"key":"2024042808492200400_ref22","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1093\/bioinformatics\/btab370","article-title":"CrossTalkeR: analysis and visualization of ligand\u2013receptor networks","volume":"37","author":"Nagai","year":"2021","journal-title":"Bioinformatics"},{"key":"2024042808492200400_ref23","doi-asserted-by":"crossref","first-page":"e72780","DOI":"10.1371\/journal.pone.0072780","article-title":"The extraction of simple relationships in growth factor-specific multiple-input and multiple-output systems in cell-fate decisions by backward elimination PLS regression","volume":"8","author":"Akimoto","year":"2013","journal-title":"PLoS One"},{"key":"2024042808492200400_ref24","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1126\/science.1116598","article-title":"A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis","volume":"310","author":"Janes","year":"2005","journal-title":"Science"},{"key":"2024042808492200400_ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-021-02286-2","article-title":"Giotto: a toolbox for integrative analysis and visualization of spatial expression data","volume":"22","author":"Dries","year":"2021","journal-title":"Genome Biol"},{"key":"2024042808492200400_ref26","doi-asserted-by":"crossref","first-page":"4868","DOI":"10.1093\/bioinformatics\/btac599","article-title":"CCPLS reveals cell-type-specific spatial dependence of transcriptomes in single cells","volume":"38","author":"Tsuchiya","year":"2022","journal-title":"Bioinformatics"},{"key":"2024042808492200400_ref27","first-page":"126","article-title":"Estimation of composition of quinoa (Chenopodium quinoa Willd.) grains by near-infrared transmission spectroscopy, LWT-food","volume":"79","author":"Encina-Zelada","year":"2017","journal-title":"Sci Technol"},{"key":"2024042808492200400_ref28","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.chemolab.2017.09.015","article-title":"Concurrent probabilistic PLS regression model and its applications in process monitoring","volume":"171","author":"Li","year":"2017","journal-title":"Chemom Intell Lab Syst"},{"key":"2024042808492200400_ref29","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/978-3-319-60801-3_27","volume-title":"Geomatic Approaches for Modeling Land Change Scenarios","author":"Taud","year":"2018"},{"key":"2024042808492200400_ref30","first-page":"24261","article-title":"Mlp-mixer: an all-mlp architecture for vision","volume":"34","author":"Tolstikhin","year":"2021","journal-title":"Adv Neural Inf Process Syst"},{"key":"2024042808492200400_ref31","doi-asserted-by":"crossref","first-page":"296","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":"2024042808492200400_ref32","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2024042808492200400_ref33","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/wics.51","article-title":"Partial least squares regression and projection on latent structure regression (PLS regression)","volume":"2","author":"Abdi","year":"2010","journal-title":"Wiley Interdiscip Rev Comput Stat"},{"key":"2024042808492200400_ref34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41232-021-00170-x","article-title":"Single-cell and spatial analyses of cancer cells: toward elucidating the molecular mechanisms of clonal evolution and drug resistance acquisition","volume":"41","author":"Nagasawa","year":"2021","journal-title":"Inflamm Regen"},{"key":"2024042808492200400_ref35","volume-title":"J Mach Learn Res","author":"Bengio"},{"key":"2024042808492200400_ref36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-15-51","article-title":"Statistical hypothesis testing of factor loading in principal component analysis and its application to metabolite set enrichment analysis","volume":"15","author":"Yamamoto","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"2024042808492200400_ref37","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc B Methodol"},{"key":"2024042808492200400_ref38","first-page":"226","article-title":"Research on K-value selection method of K-means clustering algorithm","volume":"2","author":"Yuan","year":"2019","journal-title":"J"},{"key":"2024042808492200400_ref39","doi-asserted-by":"crossref","first-page":"bbaa414","DOI":"10.1093\/bib\/bbaa414","article-title":"DSTG: deconvoluting spatial transcriptomics data through graph-based artificial intelligence","volume":"22","author":"Song","year":"2021","journal-title":"Brief Bioinform"},{"key":"2024042808492200400_ref40","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1038\/s41467-023-39717-6","article-title":"Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma","volume":"14","author":"Fang","year":"2023","journal-title":"Nat Commun"},{"key":"2024042808492200400_ref41","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":"2024042808492200400_ref42","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1093\/bioinformatics\/bty1044","article-title":"M3Drop: dropout-based feature selection for scRNASeq","volume":"35","author":"Andrews","year":"2019","journal-title":"Bioinformatics"},{"key":"2024042808492200400_ref43","doi-asserted-by":"crossref","first-page":"btad375","DOI":"10.1093\/bioinformatics\/btad375","article-title":"DeepITEH: a deep learning framework for identifying tissue-specific eRNAs from the human genome","volume":"39","author":"Zhang","year":"2023","journal-title":"Bioinformatics"},{"key":"2024042808492200400_ref44","doi-asserted-by":"crossref","first-page":"bbad316","DOI":"10.1093\/bib\/bbad316","article-title":"DeepICSH: a complex deep learning framework for identifying cell-specific silencers and their strength from the human genome","volume":"24","author":"Zhang","year":"2023","journal-title":"Brief Bioinform"},{"key":"2024042808492200400_ref45","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/annrheumdis-2014-206965","article-title":"Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return","volume":"75","author":"St\u00f6rch","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"2024042808492200400_ref46","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1038\/s41467-022-30633-9","article-title":"Identification, discrimination and heterogeneity of fibroblasts","volume":"13","author":"Lendahl","year":"2022","journal-title":"Nat Commun"},{"key":"2024042808492200400_ref47","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41577-021-00540-z","article-title":"Fibroblasts as immune regulators in infection, inflammation and cancer","volume":"21","author":"Davidson","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"2024042808492200400_ref48","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1002\/cmdc.202000160","article-title":"Pentathiepins: a novel class of glutathione peroxidase 1 inhibitors that induce oxidative stress, loss of mitochondrial membrane potential and apoptosis in human cancer cells","volume":"15","author":"Behnisch-Cornwell","year":"2020","journal-title":"ChemMedChem"},{"key":"2024042808492200400_ref49","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.neuron.2015.11.002","article-title":"Three types of cortical layer 5 neurons that differ in brain-wide connectivity and function","volume":"88","author":"Kim","year":"2015","journal-title":"Neuron"},{"key":"2024042808492200400_ref50","doi-asserted-by":"crossref","first-page":"9656","DOI":"10.1523\/JNEUROSCI.1325-14.2014","article-title":"Layer 6 corticothalamic neurons activate a cortical output layer, layer 5a","volume":"34","author":"Kim","year":"2014","journal-title":"J Neurosci"},{"key":"2024042808492200400_ref51","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00424-019-02337-5","article-title":"Complexin I knockout rats exhibit a complex neurobehavioral phenotype including profound ataxia and marked deficits in lifespan","volume":"472","author":"Xu","year":"2020","journal-title":"Pflugers Arch"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/3\/bbae198\/57347323\/bbae198.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/3\/bbae198\/57347323\/bbae198.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T08:50:01Z","timestamp":1714294201000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbae198\/7659282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,27]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbae198","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5,1]]},"published":{"date-parts":[[2024,3,27]]},"article-number":"bbae198"}}