{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:50:06Z","timestamp":1776109806466,"version":"3.50.1"},"reference-count":49,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018693","name":"H2020","doi-asserted-by":"publisher","award":["667403"],"award-info":[{"award-number":["667403"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018693","name":"H2020","doi-asserted-by":"publisher","award":["965193"],"award-info":[{"award-number":["965193"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018693","name":"H2020","doi-asserted-by":"publisher","award":["952179"],"award-info":[{"award-number":["952179"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010711","name":"Sy\u00f6p\u00e4s\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","jmdjournal.org","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Molecular Diagnostics"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1016\/j.jmoldx.2024.06.010","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T11:42:51Z","timestamp":1721994171000},"page":"931-942","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Analysis of Gene Expression Analysis Methods for RNA in Situ Hybridization Images"],"prefix":"10.1016","volume":"26","author":[{"given":"Valeria","family":"Ariotta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-268X","authenticated-orcid":false,"given":"Eros","family":"Azzalini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Canzonieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sampsa","family":"Hautaniemi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-0296","authenticated-orcid":false,"given":"Serena","family":"Bonin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jmoldx.2024.06.010_bib1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1126\/science.286.5439.531","article-title":"Molecular classification of cancer: class discovery and class prediction by gene expression monitoring","volume":"286","author":"Golub","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib2","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.gpb.2016.11.005","article-title":"Exploitation of gene expression and cancer biomarkers in paving the path to era of personalized medicine","volume":"15","author":"Kamel","year":"2017","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib3","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.7150\/jca.24744","article-title":"Gene expression detection assay for cancer clinical use","volume":"9","author":"Narrandes","year":"2018","journal-title":"J Cancer"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib4","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/415530a","article-title":"Gene expression profiling predicts clinical outcome of breast cancer","volume":"415","author":"van \u2019t Veer","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib5","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nmeth.1613","article-title":"Computational methods for transcriptome annotation and quantification using RNA-seq","volume":"8","author":"Garber","year":"2011","journal-title":"Nat Methods"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib6","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/clinchem\/48.8.1170","article-title":"Application of microarrays to the analysis of gene expression in cancer","volume":"48","author":"Macgregor","year":"2002","journal-title":"Clin Chem"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib7","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1038\/s41598-017-02217-x","article-title":"Droplet digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data","volume":"7","author":"Taylor","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib8","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/bfgp\/elu035","article-title":"Measuring differential gene expression with RNA-seq: challenges and strategies for data analysis","volume":"14","author":"Finotello","year":"2015","journal-title":"Brief Funct Genomics"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib9","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1159\/000049901","article-title":"Global analysis of gene expression: methods, interpretation, and pitfalls","volume":"10","author":"Fryer","year":"2002","journal-title":"Exp Nephrol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib10","first-page":"99","article-title":"Chapter six\u2014quantitative real-time PCR-based analysis of gene expression","volume":"vol. 500","author":"Jozefczuk","year":"2011"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib11","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/jor.23661","article-title":"Advantages of RNA-seq compared to RNA microarrays for transcriptome profiling of anterior cruciate ligament tears","volume":"36","author":"Rai","year":"2018","journal-title":"J Orthop Res"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s40291-021-00570-2","article-title":"Evaluation of the suitability of RNAscope as a technique to measure gene expression in clinical diagnostics: a systematic review","volume":"26","author":"Atout","year":"2022","journal-title":"Mol Diagn Ther"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3389\/fnins.2018.00266","article-title":"A PCR-based method for RNA probes and applications in neuroscience","volume":"12","author":"Hua","year":"2018","journal-title":"Front Neurosci"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib14","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s40291-017-0278-8","article-title":"Current and emerging applications of droplet digital PCR in oncology","volume":"21","author":"Olmedillas-L\u00f3pez","year":"2017","journal-title":"Mol Diagn Ther"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"Wang","year":"2012","journal-title":"J Mol Diagn"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib16","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-021-03634-9","article-title":"Exploring tissue architecture using spatial transcriptomics","volume":"596","author":"Rao","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib17","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-022-01448-2","article-title":"The expanding vistas of spatial transcriptomics","volume":"41","author":"Tian","year":"2023","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib18","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s41576-019-0129-z","article-title":"Spatial transcriptomics coming of age","volume":"20","author":"Burgess","year":"2019","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib19","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaa6090","article-title":"Spatially resolved, highly multiplexed RNA profiling in single cells","volume":"348","author":"Chen","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib20","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/s41374-022-00743-5","article-title":"QuantISH: RNA in situ hybridization image analysis framework for quantifying cell type-specific target RNA expression and variability","volume":"102","author":"Jamalzadeh","year":"2022","journal-title":"Lab Invest"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib21","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.cell.2014.07.001","article-title":"Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions","volume":"158","author":"Baleriola","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib22","doi-asserted-by":"crossref","first-page":"93392","DOI":"10.18632\/oncotarget.21851","article-title":"RNAscope in situ hybridization confirms mRNA integrity in formalin-fixed, paraffin-embedded cancer tissue samples","volume":"8","author":"Bingham","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib23","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1097\/PAI.0000000000000095","article-title":"Novel RNA hybridization method for the in situ detection of ETV1, ETV4 and ETV5 gene fusions in prostate cancer","volume":"22","author":"Kunju","year":"2014","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib25","article-title":"SMART-Q: an integrative pipeline quantifying cell type-specific RNA transcription","volume":"15","author":"Yang","year":"2020","journal-title":"PLoS One"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib26","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1093\/nar\/gkaa312","article-title":"dotdotdot: An automated approach to quantify multiplex single molecule fluorescent in situ hybridization (smFISH) images in complex tissues","volume":"48","author":"Maynard","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib27","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.3390\/cancers12082184","article-title":"Conditional probability of survival and prognostic factors in long-term survivors of high-grade serous ovarian cancer","volume":"12","author":"Fabbro","year":"2020","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib28","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma","volume":"474","author":"Bell","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib29","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/(SICI)1097-0215(19980105)75:1<34::AID-IJC6>3.0.CO;2-2","article-title":"Analysis of cyclin E and CDK2 in ovarian cancer: gene amplification and RNA overexpression","volume":"75","author":"Marone","year":"1998","journal-title":"Int J Cancer"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib30","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/cjp2.168","article-title":"Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma","volume":"6","author":"Chan","year":"2020","journal-title":"J Pathol Clin Res"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib31","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1158\/1541-7786.MCR-18-0034","article-title":"Biomarker assessment of HR deficiency, tumor BRCA1\/2 mutations, and CCNE1 copy number in ovarian cancer: associations with clinical outcome following platinum monotherapy","volume":"16","author":"Stronach","year":"2018","journal-title":"Mol Cancer Res"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib32","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ygyno.2023.12.021","article-title":"Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125","volume":"181","author":"AlSomairi","year":"2024","journal-title":"Gynecol Oncol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib33","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1186\/s12885-022-09887-5","article-title":"HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients","volume":"22","author":"Braicu","year":"2022","journal-title":"BMC Cancer"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib34","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.gendis.2022.07.004","article-title":"Circulating and non-circulating proteins and nucleic acids as biomarkers and therapeutic molecules in ovarian cancer","volume":"10","author":"Utkarsh","year":"2023","journal-title":"Genes Dis"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib35","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s12032-022-01665-4","article-title":"A bioinformatic analysis of WFDC2 (HE4) expression in high grade serous ovarian cancer reveals tumor-specific changes in metabolic and extracellular matrix gene expression","volume":"39","author":"James","year":"2022","journal-title":"Med Oncol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib36","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1038\/s41467-020-19408-2","article-title":"Integrated digital pathology and transcriptome analysis identifies molecular mediators of T-cell exclusion in ovarian cancer","volume":"11","author":"Desbois","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib37","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.3389\/fgene.2020.01006","article-title":"A novel six-gene signature for prognosis prediction in ovarian cancer","volume":"11","author":"Pan","year":"2020","journal-title":"Front Genet"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.acthis.2021.151765","article-title":"RNAscope compatibility with image analysis platforms for the quantification of tissue-based colorectal cancer biomarkers in archival formalin-fixed paraffin-embedded tissue","volume":"123","author":"Morley-Bunker","year":"2021","journal-title":"Acta Histochem"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib39","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/mrd.22489","article-title":"The ImageJ ecosystem: an open platform for biomedical image analysis","volume":"82","author":"Schindelin","year":"2015","journal-title":"Mol Reprod Dev"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib40","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1093\/bioinformatics\/btx180","article-title":"Trainable weka segmentation: a machine learning tool for microscopy pixel classification","volume":"33","author":"Arganda-Carreras","year":"2017","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib41","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/PAI.0000000000000542","article-title":"Cross-platform comparison of computer-assisted image analysis quantification of in situ mRNA hybridization in investigative pathology","volume":"27","author":"Holzer","year":"2019","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib42","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ygyno.2021.09.012","article-title":"Histological patterns and intra-tumor heterogeneity as prognostication tools in high grade serous ovarian cancers","volume":"163","author":"Azzalini","year":"2021","journal-title":"Gynecol Oncol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib43","article-title":"Cell-stiffness and morphological architectural patterns in clinical samples of high grade serous ovarian cancers","volume":"37","author":"Azzalini","year":"2021","journal-title":"Nanomedicine"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib44","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.cels.2020.04.003","article-title":"nucleAIzer: a parameter-free deep learning framework for nucleus segmentation using image style transfer","volume":"10","author":"Hollandi","year":"2020","journal-title":"Cell Syst"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib45","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/7832376","article-title":"PI3K\/AKT signaling in breast cancer molecular subtyping and lymph node involvement","volume":"2019","author":"Bonin","year":"2019","journal-title":"Dis Markers"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib46","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.911873","article-title":"A robust experimental and computational analysis framework at multiple resolutions, modalities and coverages","volume":"13","author":"Tran","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib47","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/ajcp\/aqx094","article-title":"Rapid loss of RNA detection by in situ hybridization in stored tissue blocks and preservation by cold storage of unstained slides","volume":"148","author":"Baena-Del Valle","year":"2017","journal-title":"Am J Clin Pathol"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib48","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/toxsci\/kfz113","article-title":"Enhanced quality metrics for assessing RNA derived from archival formalin-fixed paraffin-embedded tissue samples","volume":"170","author":"Wehmas","year":"2019","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.jmoldx.2024.06.010_bib49","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0001261","article-title":"Determinants of RNA quality from FFPE samples","volume":"2","author":"von Ahlfen","year":"2007","journal-title":"PLoS One"}],"container-title":["The Journal of Molecular Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525157824001636?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525157824001636?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T11:33:19Z","timestamp":1735558399000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525157824001636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["S1525157824001636"],"URL":"https:\/\/doi.org\/10.1016\/j.jmoldx.2024.06.010","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.02.25.581931","asserted-by":"object"}]},"ISSN":["1525-1578"],"issn-type":[{"value":"1525-1578","type":"print"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Comparative Analysis of Gene Expression Analysis Methods for RNA in Situ Hybridization Images","name":"articletitle","label":"Article Title"},{"value":"The Journal of Molecular Diagnostics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jmoldx.2024.06.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}