{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T16:09:27Z","timestamp":1758816567760},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,3,22]],"date-time":"2005-03-22T00:00:00Z","timestamp":1111449600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,3,22]],"date-time":"2005-03-22T00:00:00Z","timestamp":1111449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans show similar artefacts, which affect the analysis, particularly when one tries to detect subtle changes. However, most blemishes are hard to find by the unaided eye, particularly in high-density oligonucleotide arrays (HDONAs).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We present a method that harnesses the statistical power provided by having several HDONAs available, which are obtained under similar conditions except for the experimental factor. This method \"harshlights\" blemishes and renders them evident. We find empirically that about 25% of our chips are blemished, and we analyze the impact of masking them on screening for differentially expressed genes.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Experiments attempting to assess subtle expression changes should be carefully screened for blemishes on the chips. The proposed method provides investigators with a novel robust approach to improve the sensitivity of microarray analyses. By utilizing topological information to identify and mask blemishes prior to model based analyses, the method prevents artefacts from confounding the process of background correction, normalization, and summarization.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2105-6-65","type":"journal-article","created":{"date-parts":[[2005,3,23]],"date-time":"2005-03-23T07:16:08Z","timestamp":1111562168000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["\"Harshlighting\" small blemishes on microarrays"],"prefix":"10.1186","volume":"6","author":[{"given":"Mayte","family":"Su\u00e1rez-Fari\u00f1as","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asifa","family":"Haider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Knut M","family":"Wittkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2005,3,22]]},"reference":[{"key":"390_CR1","doi-asserted-by":"publisher","first-page":"8944","DOI":"10.1073\/pnas.161242998","volume":"98","author":"CS Brown","year":"2001","unstructured":"Brown CS, Goodwin PC, Sorger PK: Image metrics in the statistical analysis of DNA microarray data. PNAS 2001, 98: 8944\u20138949. 10.1073\/pnas.161242998","journal-title":"PNAS"},{"key":"390_CR2","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1101\/gr.210902","volume":"12","author":"AN Jain","year":"2002","unstructured":"Jain AN, Tokuyasu TA, Snijders AM, Segraves R, Albertson DG, Pinkel D: Fully Automatic Quantification of Microarray Image Data. Genome Res 2002, 12: 325\u2013332. 10.1101\/gr.210902","journal-title":"Genome Res"},{"key":"390_CR3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/10618600.1996.10474713","volume":"5","author":"R Ihaka","year":"1996","unstructured":"Ihaka R, Gentleman R: A language for data analysis and graphics. Journal of Computational and Graphical Statistics 1996, 5: 299\u2013314.","journal-title":"Journal of Computational and Graphical Statistics"},{"key":"390_CR4","doi-asserted-by":"publisher","DOI":"10.1007\/b97411","volume-title":"The analysis of gene expression data: methods and software","author":"G Parmigiani","year":"2003","unstructured":"Parmigiani G, Garrett ES, Irizarry RA, Zeger SL: The analysis of gene expression data: methods and software. New York: Springer; 2003."},{"key":"390_CR5","volume-title":"GeneChip Expression Analysis: Data Analysis Fundamentals","author":"Affymetrix I","year":"2004","unstructured":"Affymetrix I: GeneChip Expression Analysis: Data Analysis Fundamentals. 2004."},{"key":"390_CR6","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1093\/bioinformatics\/btg275","volume":"19","author":"S Hautaniemi","year":"2003","unstructured":"Hautaniemi S, Edgren H, Vesanen P, Wolf M, Jarvinen A-K, Yli-Harja O, Astola J, Kallioniemi O, Monni O: A novel strategy for microarray quality control using Bayesian networks. Bioinformatics 2003, 19: 2031\u20132038. 10.1093\/bioinformatics\/btg275","journal-title":"Bioinformatics"},{"key":"390_CR7","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","volume":"4","author":"RA Irizarry","year":"2003","unstructured":"Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003, 4: 249\u2013264. 10.1093\/biostatistics\/4.2.249","journal-title":"Biostatistics"},{"key":"390_CR8","doi-asserted-by":"publisher","first-page":"011906","DOI":"10.1103\/PhysRevE.68.011906","volume":"68","author":"F Naef","year":"2003","unstructured":"Naef F, Magnasco MO: Solving the riddle of the bright mismatches: labeling and effective binding in oligonucleotide arrays. Phys Rev E Stat Nonlin Soft Matter Phys 2003, 68: 011906. Epub 012003 Jul 011916.","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"key":"390_CR9","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1198\/016214504000000683","volume":"99","author":"Z Wu","year":"2004","unstructured":"Wu Z, Irizarry RA, Gentleman R, Martinez Murillo F, Spencer F: A model based background adjustment for oligonucleotide expression arrays. Journal of the American Statistical Association 2004, 99: 909\u2013917. 10.1198\/016214504000000683","journal-title":"Journal of the American Statistical Association"},{"key":"390_CR10","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.it.2004.03.006","volume":"25","author":"W Lew","year":"2004","unstructured":"Lew W, Bowcock AM, Krueger JG: Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and 'Type 1' inflammatory gene expression. Trends in Immunology 2004, 25: 295\u2013305. 10.1016\/j.it.2004.03.006","journal-title":"Trends in Immunology"},{"key":"390_CR11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1152\/physiolgenomics.00157.2002","volume":"13","author":"X Zhou","year":"2003","unstructured":"Zhou X, Krueger JG, Kao M-CJ, Lee E, Du F, Menter A, Wong WH, Bowcock AM: Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array. Physiol Genomics 2003, 13: 69\u201378.","journal-title":"Physiol Genomics"},{"key":"390_CR12","volume-title":"European Academy of Dermatology and Venereology; Florence, IT","author":"AI Bayliffe","year":"2004","unstructured":"Bayliffe AI, Haider A, Haws TF, Kaplow Y, Krueger JG, Liy AG, Thompson PW, Wang X-J, Lamb JR: PPAR-g mechanisms in reducing cutaneus inflammation. European Academy of Dermatology and Venereology; Florence, IT 2004."},{"key":"390_CR13","volume-title":"Design and Analysis of DNA Microarray Investigations","author":"RM Simon","year":"2003","unstructured":"Simon RM, Korn EL, McShane LM, Radmacher MD, Wright GW, Zhao Y: Design and Analysis of DNA Microarray Investigations. New York: Springer; 2003."},{"key":"390_CR14","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1103\/PhysRevE.61.475","volume":"61","author":"RD Deegan","year":"2000","unstructured":"Deegan RD: Pattern formation in drying drops. Physical Review E 2000, 61: 475\u2013485. 10.1103\/PhysRevE.61.475","journal-title":"Physical Review E"},{"key":"390_CR15","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2202\/1544-6115.1027","volume":"3","author":"GK Smyth","year":"2004","unstructured":"Smyth GK: Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology 2004, 3: 3.","journal-title":"Statistical Applications in Genetics and Molecular Biology"},{"key":"390_CR16","unstructured":"Website title[http:\/\/www.bioconductor.org]"},{"key":"390_CR17","unstructured":"Website title[http:\/\/www.affymetrix.com\/analysis\/download_center2.affx]"},{"key":"390_CR18","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1093\/bioinformatics\/btg410","volume":"20","author":"L Cope","year":"2004","unstructured":"Cope L, Irizarry R, Jaffee H, Wu Z, Speed T: A benchmark for affymetrix GeneChip expression measures. BIOINFORMATICS 2004, 20: 323\u2013331. 10.1093\/bioinformatics\/btg410","journal-title":"BIOINFORMATICS"},{"key":"390_CR19","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1073\/pnas.98.1.31","volume":"98","author":"C Li","year":"2001","unstructured":"Li C, Wong WH: Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection. PNAS 2001, 98: 31\u201336. 10.1073\/pnas.011404098","journal-title":"PNAS"},{"key":"390_CR20","volume-title":"Affymetrix GeneChip Microarray Low-Level Workshop; Berkeley, UC","author":"F Collin","year":"2003","unstructured":"Collin F, Brettschneider J, Bolstad B, Speed T: Quality Assessment of Gene Expression Data for Affymetrix Genechips. Affymetrix GeneChip Microarray Low-Level Workshop; Berkeley, UC 2003."},{"key":"390_CR21","volume-title":"Linear Models","author":"SR Searle","year":"1971","unstructured":"Searle SR: Linear Models. New York: Wiley; 1971."}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-6-65.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1471-2105-6-65\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-6-65.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T12:08:48Z","timestamp":1728302928000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-6-65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,22]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2005,12]]}},"alternative-id":["390"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-6-65","relation":{},"ISSN":["1471-2105"],"issn-type":[{"type":"electronic","value":"1471-2105"}],"subject":[],"published":{"date-parts":[[2005,3,22]]},"assertion":[{"value":"26 October 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2005","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2005","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"65"}}