{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:39:05Z","timestamp":1791308345722,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011365","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000}}],"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["5U54 DA036134"],"award-info":[{"award-number":["5U54 DA036134"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["U54CA224076"],"award-info":[{"award-number":["U54CA224076"]}]},{"name":"CPRIT Core Facility","award":["RP170691"],"award-info":[{"award-number":["RP170691"]}]},{"name":"P30 Cancer Center Support Grant","award":["NC-CA125123"],"award-info":[{"award-number":["NC-CA125123"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Proper characterization of cancer cell states within the tumor microenvironment is a key to accurately identifying matching experimental models and the development of precision therapies. To reconstruct this information from bulk RNA-seq profiles, we developed the XDec Simplex Mapping (XDec-SM) reference-optional deconvolution method that maps tumors and the states of constituent cells onto a biologically interpretable low-dimensional space. The method identifies gene sets informative for deconvolution from relevant single-cell profiling data when such profiles are available. When applied to breast tumors in The Cancer Genome Atlas (TCGA), XDec-SM infers the identity of constituent cell types and their proportions. XDec-SM also infers cancer cells states within individual tumors that associate with DNA methylation patterns, driver somatic mutations, pathway activation and metabolic coupling between stromal and breast cancer cells. By projecting tumors, cancer cell lines, and PDX models onto the same map, we identify <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models with matching cancer cell states. Map position is also predictive of therapy response, thus opening the prospects for precision therapy informed by experiments in model systems matched to tumors <jats:italic>in vivo<\/jats:italic> by cancer cell state.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011365","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T17:29:49Z","timestamp":1692034189000},"page":"e1011365","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deconvolution of cancer cell states by the XDec-SM method"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1938-3905","authenticated-orcid":true,"given":"Oscar D.","family":"Murillo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varduhi","family":"Petrosyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"LaPlante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey E.","family":"Dobrolecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Milosavljevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"pcbi.1011365.ref001","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tranon.2018.01.011","article-title":"A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer.","volume":"11","author":"Z Liu","year":"2018","journal-title":"Transl Oncol"},{"key":"pcbi.1011365.ref002","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41586-020-1969-6","article-title":"Pan-cancer analysis of whole genomes","volume":"578","author":"PJ Campbell","year":"2020","journal-title":"Nature"},{"key":"pcbi.1011365.ref003","first-page":"169","article-title":"Novel Biomarkers in the Continuum of Breast Cancer","volume":"882","author":"F Beca","year":"2016","journal-title":"Adv Exp Med Biol"},{"key":"pcbi.1011365.ref004","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/bcr2912","article-title":"The microenvironment in breast cancer progression: biology and implications for treatment","volume":"13","author":"AE Place","year":"2011","journal-title":"Breast Cancer Res"},{"key":"pcbi.1011365.ref005","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.trecan.2019.11.010","article-title":"Tumor Functional Heterogeneity Unraveled by scRNA-seq Technologies","volume":"6","author":"L Gonz\u00e1lez-Silva","year":"2020","journal-title":"Trends Cancer"},{"key":"pcbi.1011365.ref006","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.1038\/s41467-018-06052-0","article-title":"Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq.","volume":"9","author":"M Karaayvaz","year":"2018","journal-title":"Nat Commun"},{"key":"pcbi.1011365.ref007","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"AP Patel","year":"2014","journal-title":"Science"},{"key":"pcbi.1011365.ref008","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.cell.2017.10.044","article-title":"Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer","volume":"171","author":"SV Puram","year":"2017","journal-title":"Cell"},{"key":"pcbi.1011365.ref009","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3389\/fgene.2019.00317","article-title":"Single-Cell RNA-Seq Technologies and Related Computational Data Analysis.","volume":"10","author":"G Chen","year":"2019","journal-title":"Frontiers Genetics"},{"key":"pcbi.1011365.ref010","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13073-017-0467-4","article-title":"A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.","volume":"9","author":"A Haque","year":"2017","journal-title":"Genome Med"},{"key":"pcbi.1011365.ref011","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13059-016-0888-1","article-title":"Classification of low quality cells from single-cell RNA-seq data","volume":"17","author":"T Ilicic","year":"2016","journal-title":"Genome Biol"},{"key":"pcbi.1011365.ref012","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.molcel.2015.04.005","article-title":"The Technology and Biology of Single-Cell RNA Sequencing","volume":"58","author":"AA Kolodziejczyk","year":"2015","journal-title":"Mol Cell"},{"key":"pcbi.1011365.ref013","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","author":"AM Newman","year":"2019","journal-title":"Nat Biotechnol"},{"key":"pcbi.1011365.ref014","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41467-018-08023-x","article-title":"Bulk tissue cell type deconvolution with multi-subject single-cell expression reference","volume":"10","author":"X Wang","year":"2019","journal-title":"Nat Commun"},{"key":"pcbi.1011365.ref015","doi-asserted-by":"crossref","first-page":"5482","DOI":"10.1016\/j.cell.2021.09.014","article-title":"Atlas of clinically distinct cell states and ecosystems across human solid tumors","volume":"184","author":"BA Luca","year":"2021","journal-title":"Cell"},{"key":"pcbi.1011365.ref016","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/j.celrep.2016.10.057","article-title":"Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types","volume":"17","author":"V Onuchic","year":"2016","journal-title":"Cell Reports"},{"key":"pcbi.1011365.ref017","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12859-019-3307-2","article-title":"Guidelines for cell-type heterogeneity quantification based on a comparative analysis of reference-free DNA methylation deconvolution software","volume":"21","author":"C Decamps","year":"2020","journal-title":"Bmc Bioinformatics"},{"key":"pcbi.1011365.ref018","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1200\/JCO.2008.18.1370","article-title":"Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes.","volume":"27","author":"JS Parker","year":"2009","journal-title":"J Clin Oncol"},{"key":"pcbi.1011365.ref019","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.ccell.2022.07.006","article-title":"Precise reconstruction of the TME using bulk RNA-seq and a machine learning algorithm trained on artificial transcriptomes","volume":"40","author":"A Zaitsev","year":"2022","journal-title":"Cancer Cell"},{"key":"pcbi.1011365.ref020","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-1-0716-0327-7_17","article-title":"EPIC: A Tool to Estimate the Proportions of Different Cell Types from Bulk Gene Expression Data.","volume":"2120","author":"J Racle","year":"2020","journal-title":"Methods Mol Biology Clifton N J"},{"key":"pcbi.1011365.ref021","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"D Aran","year":"2017","journal-title":"Genome Biol"},{"key":"pcbi.1011365.ref022","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1093\/bioinformatics\/btv370","article-title":"Predicting tumor purity from methylation microarray data","volume":"31","author":"N Zhang","year":"2015","journal-title":"Bioinformatics"},{"key":"pcbi.1011365.ref023","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells","volume":"77","author":"T Li","year":"2017","journal-title":"Cancer Res"},{"key":"pcbi.1011365.ref024","doi-asserted-by":"crossref","first-page":"15081","DOI":"10.1038\/ncomms15081","article-title":"Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer","volume":"8","author":"W Chung","year":"2017","journal-title":"Nat Commun"},{"key":"pcbi.1011365.ref025","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.cell.2018.03.041","article-title":"Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing","volume":"173","author":"C Kim","year":"2018","journal-title":"Cell"},{"key":"pcbi.1011365.ref026","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1158\/1078-0432.CCR-15-2851","article-title":"Fibroblast Subtypes Regulate Responsiveness of Luminal Breast Cancer to Estrogen","volume":"23","author":"HM Brechbuhl","year":"2017","journal-title":"Clin Cancer Res"},{"key":"pcbi.1011365.ref027","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1038\/s41467-018-05220-6","article-title":"Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer","volume":"9","author":"AS Cazet","year":"2018","journal-title":"Nat Commun"},{"key":"pcbi.1011365.ref028","doi-asserted-by":"crossref","first-page":"664","DOI":"10.3390\/cancers11050664","article-title":"Breast Cancer Tumor Stroma: Cellular Components, Phenotypic Heterogeneity, Intercellular Communication, Prognostic Implications and Therapeutic Opportunities.","volume":"11","author":"N Eiro","year":"2019","journal-title":"Cancers"},{"key":"pcbi.1011365.ref029","doi-asserted-by":"crossref","first-page":"3736","DOI":"10.7150\/jca.28054","article-title":"Activated Tumor-infiltrating Fibroblasts Predict Worse Prognosis in Breast Cancer Patients.","volume":"9","author":"G Hu","year":"2018","journal-title":"J Cancer"},{"key":"pcbi.1011365.ref030","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s10555-012-9415-3","article-title":"Stromal cells in tumor microenvironment and breast cancer","volume":"32","author":"Y Mao","year":"2013","journal-title":"Cancer Metast Rev"},{"key":"pcbi.1011365.ref031","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cell.2005.02.034","article-title":"Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1\/CXCL12 Secretion","volume":"121","author":"A Orimo","year":"2005","journal-title":"Cell"},{"key":"pcbi.1011365.ref032","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12943-019-0960-z","article-title":"Recent advances in understanding tumor stroma-mediated chemoresistance in breast cancer","volume":"18","author":"J Plava","year":"2019","journal-title":"Mol Cancer"},{"key":"pcbi.1011365.ref033","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.3390\/cancers7040902","article-title":"Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth.","volume":"7","author":"K Shiga","year":"2015","journal-title":"Cancers"},{"key":"pcbi.1011365.ref034","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.pathol.2016.10.009","article-title":"The biological and clinical significance of stromal-epithelial interactions in breast cancer","volume":"49","author":"R McCuaig","year":"2017","journal-title":"Pathology"},{"key":"pcbi.1011365.ref035","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.blre.2015.01.004","article-title":"Information transfer by exosomes: A new frontier in hematologic malignancies","volume":"29","author":"M Boyiadzis","year":"2015","journal-title":"Blood Rev"},{"key":"pcbi.1011365.ref036","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.semcancer.2013.12.005","article-title":"Regulation of the anti-tumour immune response by cancer-associated fibroblasts","volume":"25","author":"J Harper","year":"2014","journal-title":"Semin Cancer Biol"},{"key":"pcbi.1011365.ref037","doi-asserted-by":"crossref","first-page":"7884","DOI":"10.1158\/0008-5472.CAN-09-1451","article-title":"Blockade of a Chemokine, CCL2, Reduces Chronic Colitis-Associated Carcinogenesis in Mice","volume":"69","author":"BK Popivanova","year":"2009","journal-title":"Cancer Res"},{"key":"pcbi.1011365.ref038","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.semcancer.2014.01.005","article-title":"Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth","volume":"25","author":"UE Martinez-Outschoorn","year":"2014","journal-title":"Semin Cancer Biol"},{"key":"pcbi.1011365.ref039","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nrc3915","article-title":"Caveolae and signalling in cancer","volume":"15","author":"UE Martinez-Outschoorn","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"pcbi.1011365.ref040","doi-asserted-by":"crossref","first-page":"e0125728","DOI":"10.1371\/journal.pone.0125728","article-title":"Prognostic Value of Tumor-Associated Macrophages According to Histologic Locations and Hormone Receptor Status in Breast Cancer.","volume":"10","author":"JM Gwak","year":"2015","journal-title":"Plos One"},{"key":"pcbi.1011365.ref041","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.humpath.2017.09.001","article-title":"Tumor-associated macrophages are strongly related to vascular invasion, non-luminal subtypes, and interval breast cancer","volume":"69","author":"TA Klingen","year":"2017","journal-title":"Hum Pathol"},{"key":"pcbi.1011365.ref042","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/1878-0261.12319","article-title":"Basal-like breast cancer engages tumor-supportive macrophages via secreted factors induced by extracellular S100A4.","volume":"12","author":"L Prasmickaite","year":"2018","journal-title":"Mol Oncol."},{"key":"pcbi.1011365.ref043","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3332\/ecancer.2020.1027","article-title":"Neoadjuvant endocrine therapy for luminal breast cancer treatment: a first-choice alternative in times of crisis, such as the COVID-19 pandemic.","volume":"14","author":"C Marti","year":"2020","journal-title":"Ecancermedicalscience."},{"key":"pcbi.1011365.ref044","doi-asserted-by":"crossref","first-page":"7956","DOI":"10.1038\/s41598-019-44339-4","article-title":"PCA-PAM50 improves consistency between breast cancer intrinsic and clinical subtyping reclassifying a subset of luminal A tumors as luminal B","volume":"9","author":"P-K Raj-Kumar","year":"2019","journal-title":"Sci Rep-uk"},{"key":"pcbi.1011365.ref045","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1186\/s12864-016-2911-z","article-title":"Comprehensive comparison of molecular portraits between cell lines and tumors in breast cancer","volume":"17","author":"G Jiang","year":"2016","journal-title":"Bmc Genomics"},{"key":"pcbi.1011365.ref046","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-019-1186-3","article-title":"Next-generation characterization of the Cancer Cell Line Encyclopedia","volume":"569","author":"M Ghandi","year":"2019","journal-title":"Nature"},{"key":"pcbi.1011365.ref047","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s42003-020-1042-x","article-title":"Chemogenomic profiling of breast cancer patient-derived xenografts reveals targetable vulnerabilities for difficult-to-treat tumors","volume":"3","author":"P Savage","year":"2020","journal-title":"Commun Biology"},{"key":"pcbi.1011365.ref048","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nbt.3838","article-title":"Reproducible RNA-seq analysis using recount2","volume":"35","author":"L Collado-Torres","year":"2017","journal-title":"Nat Biotechnol"},{"key":"pcbi.1011365.ref049","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.1158\/1078-0432.CCR-10-1282","article-title":"A Comparison of PAM50 Intrinsic Subtyping with Immunohistochemistry and Clinical Prognostic Factors in Tamoxifen-Treated Estrogen Receptor\u2013Positive Breast Cancer","volume":"16","author":"TO Nielsen","year":"2010","journal-title":"Clin Cancer Res"},{"key":"pcbi.1011365.ref050","doi-asserted-by":"crossref","first-page":"5306","DOI":"10.1016\/j.cell.2021.09.028","article-title":"Deciphering the cancer microenvironment from bulk data with EcoTyper","volume":"184","author":"A Rolong","year":"2021","journal-title":"Cell"},{"key":"pcbi.1011365.ref051","doi-asserted-by":"crossref","first-page":"105249","DOI":"10.1016\/j.isci.2022.105249","article-title":"XDec-CHI reveals immunosuppressive interactions in pancreatic ductal adenocarcinoma.","volume":"25","author":"EL LaPlante","year":"2022","journal-title":"iScience."},{"key":"pcbi.1011365.ref052","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/bcr2889","article-title":"Choosing the right cell line for breast cancer research","volume":"13","author":"DL Holliday","year":"2011","journal-title":"Breast Cancer Res"},{"key":"pcbi.1011365.ref053","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.cell.2019.02.018","article-title":"exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids","volume":"177","author":"OD Murillo","year":"2019","journal-title":"Cell"},{"key":"pcbi.1011365.ref054","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13059-016-0947-7","article-title":"Pooling across cells to normalize single-cell RNA sequencing data with many zero counts","volume":"17","author":"ATL Lun","year":"2016","journal-title":"Genome Biol"},{"key":"pcbi.1011365.ref055","doi-asserted-by":"crossref","first-page":"e26476","DOI":"10.7554\/eLife.26476","article-title":"Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data","volume":"6","author":"J Racle","year":"2017","journal-title":"Elife"},{"key":"pcbi.1011365.ref056","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.gendis.2018.02.003","article-title":"InfiniumPurify: An R package for estimating and accounting for tumor purity in cancer methylation research","volume":"5","author":"Y Qin","year":"2018","journal-title":"Genes Dis"},{"key":"pcbi.1011365.ref057","first-page":"87","article-title":"ggtern: Ternary Diagrams Using ggplot2.","author":"NE Hamilton","year":"2018","journal-title":"J Stat Softw."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011365","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011365","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T17:53:52Z","timestamp":1692899632000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011365"}},"subtitle":[],"editor":[{"given":"Zhaolei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,8,14]]},"references-count":57,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011365","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1011365","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,14]]}}}