{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:01:08Z","timestamp":1787068868556,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["FFABR2017"],"award-info":[{"award-number":["FFABR2017"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Transcriptomics studies have been facilitated by the development of microarray and RNA-Seq technologies, with thousands of expression datasets available for many species. However, the quality of data can be highly variable, making the combined analysis of different datasets difficult and unreliable. Most of the microarray data for Medicago truncatula, the barrel medic, have been stored and made publicly accessible on the web database Medicago truncatula Gene Expression atlas (MtGEA). The aim of this work is to ameliorate the quality of the MtGEA database through a general method based on logical and statistical relationships among parameters and conditions. The initial 716 columns available in the dataset were reduced to 607 by evaluating the quality of data through the sum of the expression levels over the entire transcriptome probes and Pearson correlation among hybridizations. The reduced dataset shows great improvements in the consistency of the data, with a reduction in both false positives and false negatives resulting from Pearson correlation and GO enrichment analysis among genes. The approach we used is of general validity and our intent is to extend the analysis to other plant microarray databases.<\/jats:p>","DOI":"10.3390\/plants10061240","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T11:19:20Z","timestamp":1624015160000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cleaning the Medicago Microarray Database to Improve Gene Function Analysis"],"prefix":"10.3390","volume":"10","author":[{"given":"Francesca","family":"Marzorati","sequence":"first","affiliation":[{"name":"Department of Environmental Science and Policy, University of Milan, Via Celoria 10, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4336-6075","authenticated-orcid":false,"given":"Chu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Pavesi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mizzi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-6426","authenticated-orcid":false,"given":"Piero","family":"Morandini","sequence":"additional","affiliation":[{"name":"Department of Environmental Science and Policy, University of Milan, Via Celoria 10, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1576\/toag.13.3.189.27672","article-title":"\u201cOmic\u201d technologies: Genomics, transcriptomics, proteomics and metabolomics","volume":"13","author":"Richard","year":"2011","journal-title":"Obstet. Gynaecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.molp.2016.05.003","article-title":"Plant Ionomics: From Elemental Profiling to Environmental Adaptation","volume":"9","author":"Huang","year":"2016","journal-title":"Mol. Plant"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pcbi.1005457","article-title":"Transcriptomics technologies","volume":"13","author":"Lowe","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/ng1032","article-title":"Microarray data normalization and transformation","volume":"32","author":"Quackenbush","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Park, T., Yi, S.G., Kang, S.H., Lee, S.Y., Lee, Y.S., and Simon, R. (2003). Evaluation of normalization methods for microarray data. BMC Bioinform., 4.","DOI":"10.1186\/1471-2105-4-33"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Slonim, D.K., and Yanai, I. (2009). Getting started in gene expression microarray analysis. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000543"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bumgarner, R. (2013). Overview of DNA microarrays: Types, applications, and their future. Curr. Protoc. Mol. Biol., 1\u201311.","DOI":"10.1002\/0471142727.mb2201s101"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/455847a","article-title":"The death of microarrays?","volume":"455","author":"Ledford","year":"2008","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: Archive for functional genomics data sets\u2014Update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/nar\/29.1.102","article-title":"The Arabidopsis Information Resource (TAIR): A comprehensive database and web-based information retrieval, analysis, and visualization system for a model plant","volume":"29","author":"Huala","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/j.1365-313X.2008.03519.x","article-title":"A gene expression atlas of the model legume Medicago truncatula","volume":"55","author":"Benedito","year":"2008","journal-title":"Plant J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"He, J., Benedito, V.A., Wang, M., Murray, J.D., Zhao, P.X., Tang, Y., and Udvardi, M.K. (2009). The Medicago truncatula gene expression atlas web server. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-441"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1039\/c3np70104b","article-title":"Natural product biosynthesis in Medicago species","volume":"31","author":"Gholami","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kang, Y., Li, M., Sinharoy, S., and Verdier, J. (2016). A snapshot of functional genetic studies in Medicago truncatula. Front. Plant Sci., 7.","DOI":"10.3389\/fpls.2016.01175"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/BF02668879","article-title":"Medicago truncatula, a model plant for studying the molecular genetics of the Rhizobium-legume symbiosis","volume":"8","author":"Barker","year":"1990","journal-title":"Plant Mol. Biol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1104\/pp.017004","article-title":"Update on Legume Utilization Legumes: Importance and Constraints to Greater Use","volume":"131","author":"Graham","year":"2003","journal-title":"Plant Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nature10625","article-title":"The Medicago genome provides insight into the evolution of rhizobial symbioses","volume":"480","author":"Young","year":"2011","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1093\/nar\/gkr939","article-title":"LegumeIP: An integrative database for comparative genomics and transcriptomics of model legumes","volume":"40","author":"Li","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, M., Verdier, J., Benedito, V.A., Tang, Y., Murray, J.D., Ge, Y., Becker, J.D., Carvalho, H., Rogers, C., and Udvardi, M. (2013). LegumeGRN: A Gene Regulatory Network Prediction Server for Functional and Comparative Studies. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067434"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0076-6879(06)10001-4","article-title":"The Affymetrix GeneChip\u00ae Platform: An Overview","volume":"Volume 410","author":"Warrington","year":"2006","journal-title":"Methods in Enzymology"},{"key":"ref_22","first-page":"706","article-title":"Correlation analysis","volume":"1\u20133","author":"Franzese","year":"2018","journal-title":"Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tjem.2018.08.001","article-title":"User\u2019s guide to correlation coefficients","volume":"18","author":"Akoglu","year":"2018","journal-title":"Turk. J. Emerg. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.jplph.2010.11.020","article-title":"Arabidopsis CYP82C4 expression is dependent on Fe availability and circadian rhythm, and correlates with genes involved in the early Fe deficiency response","volume":"168","author":"Murgia","year":"2011","journal-title":"J. Plant Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17905","DOI":"10.1074\/jbc.M400589200","article-title":"Pearson Correlation Analysis of Microarray Data Allows for the Identification of Genetic Targets for Early B-cell Factor","volume":"279","author":"Tsapogas","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/aob\/mcv066","article-title":"Identification of the arabidopsis RAM\/MOR signalling network: Adding new regulatory players in plant stem cell maintenance and cell polarization","volume":"116","author":"Zermiani","year":"2015","journal-title":"Ann. Bot."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Beekweelder, J., van Leeuwen, W., van Dam, N.M., Bertossi, M., Grandi, V., Mizzi, L., Soloviev, M., Szabados, L., Molthoff, J.W., and Schipper, B. (2008). The impact of the absence of aliphatic glucosinolates on insect herbivory in Arabidopsis. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002068"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1105\/tpc.109.073270","article-title":"Genomic and coexpression analyses predict multiple genes involved in triterpene saponin biosynthesis in Medicago truncatula","volume":"22","author":"Naoumkina","year":"2010","journal-title":"Plant Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrg2363","article-title":"Use and misuse of the gene ontology annotations","volume":"9","author":"Wood","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1365-313X.2011.04810.x","article-title":"Arbuscule-containing and non-colonized cortical cells of mycorrhizal roots undergo extensive and specific reprogramming during arbuscular mycorrhizal development","volume":"69","author":"Gaude","year":"2012","journal-title":"Plant J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hogekamp, C., and K\u00fcster, H. (2013). A roadmap of cell-type specific gene expression during sequential stages of the arbuscular mycorrhiza symbiosis. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-306"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Limpens, E., Moling, S., Hooiveld, G., Pereira, P.A., Bisseling, T., Becker, J.D., and K\u00fcster, H. (2013). Cell- and Tissue-Specific Transcriptome Analyses of Medicago truncatula Root Nodules. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064377"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/mp\/sss027","article-title":"Plant genes related to gibberellin biosynthesis and signaling are differentially regulated during the early Stages of AM fungal interactions","volume":"5","author":"Ortu","year":"2012","journal-title":"Mol. Plant"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1094\/MPMI-12-11-0322","article-title":"Inhibition of glutamine synthetase by phosphinothricin leads to transcriptome reprograming in root nodules of Medicago truncatula","volume":"25","author":"Seabra","year":"2012","journal-title":"Mol. Plant Microbe Interact."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1093\/mp\/sss015","article-title":"Structure and Dynamics of the Isoprenoid Pathway Network","volume":"5","author":"Coman","year":"2012","journal-title":"Mol. Plant"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/BF02703339","article-title":"An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants","volume":"28","author":"Dubey","year":"2003","journal-title":"J. Biosci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Savage, G.P. (2003). Saponins. Encyclopedia of Food Science and Nutrition, Academic Press. [2nd ed.].","DOI":"10.1016\/B0-12-227055-X\/01050-6"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s11101-010-9169-x","article-title":"Biosynthesis of saponins in the genus Medicago","volume":"10","author":"Tava","year":"2011","journal-title":"Phytochem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/978-1-4939-8633-0_20","article-title":"Functional genomics in the study of metabolic pathways in Medicago truncatula: An overview","volume":"1822","author":"Liu","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.bbrc.2018.07.123","article-title":"Transcriptional regulation of bHLH during plant response to stress","volume":"503","author":"Sun","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1105\/tpc.013839","article-title":"The Arabidopsis Basic\/Helix-Loop-Helix Transcription Factor Family","volume":"15","author":"Huq","year":"2003","journal-title":"Plant Cell"},{"key":"ref_43","first-page":"D1104","article-title":"PlantRegMap: Charting functional regulatory maps in plants","volume":"48","author":"Tian","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"D1040","DOI":"10.1093\/nar\/gkw982","article-title":"PlantTFDB 4.0: Toward a central hub for transcription factors and regulatory interactions in plants","volume":"45","author":"Jin","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/nar\/gkq310","article-title":"agriGO: A GO analysis toolkit for the agricultural community","volume":"38","author":"Du","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W122","DOI":"10.1093\/nar\/gkx382","article-title":"AgriGO v2.0: A GO analysis toolkit for the agricultural community, 2017 update","volume":"45","author":"Tian","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1126\/science.274.5289.998","article-title":"Laser Capture Microdissection","volume":"274","author":"Bonner","year":"1996","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8093","DOI":"10.1021\/jf048053d","article-title":"The impact of saponins or saponin-containing plant materials on ruminant production\u2014A review","volume":"53","author":"Wina","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1105\/tpc.111.087312","article-title":"Medicago truncatula CYP716A12 is a multifunctional oxidase involved in the biosynthesis of hemolytic saponins","volume":"23","author":"Carelli","year":"2011","journal-title":"Plant Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1104\/pp.109.141481","article-title":"Integrated metabolite and transcript profiling identify a biosynthetic mechanism for hispidol in Medicago truncatula cell cultures","volume":"151","author":"Farag","year":"2009","journal-title":"Plant Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2229-8-132","article-title":"Elicitor-induced transcription factors for metabolic reprogramming of secondary metabolism in Medicago truncatula","volume":"8","author":"Naoumkina","year":"2008","journal-title":"BMC Plant Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/biostatistics\/kxv026","article-title":"Correcting gene expression data when neither the unwanted variation nor the factor of interest are observed","volume":"17","author":"Jacob","year":"2016","journal-title":"Biostatistics"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Freytag, S., Gagnon-Bartsch, J., and Speed, T.P. (2015). Systematic noise degrades gene co-expression signals but can be corrected. BMC Bioinform., 16.","DOI":"10.1186\/s12859-015-0745-3"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Varma, S. (2020). Blind estimation and correction of microarray batch effect. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231446"},{"key":"ref_55","unstructured":"R Core Team (2020). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_56","unstructured":"Wickham, H. (2021, April 15). ggplot2: Create Elegant Data Visualisations Using the Grammar of Graphics, Available online: https:\/\/cran.r-project.org\/web\/packages\/ggplot2\/index.html."},{"key":"ref_57","unstructured":"Kolde, R. (2021, April 15). pheatmap: Pretty Heatmaps, Available online: https:\/\/cran.r-project.org\/web\/packages\/pheatmap\/index.html."},{"key":"ref_58","unstructured":"Dowle, M. (2021, April 15). Package \u201cData.Table\u201d, Available online: https:\/\/cran.r-project.org\/web\/packages\/data.table\/index.html."},{"key":"ref_59","unstructured":"Harrell, F.E. (2021, April 15). Package \u201cHmisc\u201d, Available online: https:\/\/cran.r-project.org\/web\/packages\/Hmisc\/index.html."},{"key":"ref_60","unstructured":"Neuwirth, E. (2021, April 15). Package \u201cRColorBrewer\u201d, Available online: https:\/\/cran.r-project.org\/web\/packages\/RColorBrewer\/index.html."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1111\/j.1365-294X.2012.05629.x","article-title":"Coevolutionary genetic variation in the legume-rhizobium transcriptome","volume":"21","author":"Heath","year":"2012","journal-title":"Mol. Ecol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1094\/MPMI-22-1-0007","article-title":"Global gene expression profiling during Medicago truncatula-Phymatotrichopsis omnivora interaction reveals a role for jasmonic acid, ethylene, and the flavonoid pathway in disease development","volume":"22","author":"Uppalapati","year":"2009","journal-title":"Mol. Plant Microbe Interact."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/10\/6\/1240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:18:22Z","timestamp":1760163502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/10\/6\/1240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,18]]},"references-count":63,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["plants10061240"],"URL":"https:\/\/doi.org\/10.3390\/plants10061240","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,18]]}}}