{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:07:57Z","timestamp":1761487677722,"version":"3.32.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: The systematic integration of expression profiles and other types of gene information, such as chromosomal localization, ontological annotations and sequence characteristics, still represents a challenge in the gene expression arena. In particular, the analysis of transcriptional data in context of the physical location of genes in a genome appears promising in detecting chromosomal regions with transcriptional imbalances often characterizing cancer.<\/jats:p><jats:p>Results: A computational tool named locally adaptive statistical procedure (LAP), which incorporates transcriptional data and structural information for the identification of differentially expressed chromosomal regions, is described. LAP accounts for variations in the distance between genes and in gene density by smoothing standard statistics on gene position before testing the significance of their differential levels of gene expression. The procedure smoothes parameters and computes p-values locally to account for the complex structure of the genome and to more precisely estimate the differential expression of chromosomal regions. The application of LAP to three independent sets of raw expression data allowed identifying differentially expressed regions that are directly involved in known chromosomal aberrations characteristic of tumors.<\/jats:p><jats:p>Availability: Functions in R for implementing the LAP method are available at<\/jats:p><jats:p>Contact: \u00a0silvio.bicciato@unipd.it<\/jats:p><jats:p>Supplementary Information: \u00a0<\/jats:p>","DOI":"10.1093\/bioinformatics\/btl455","type":"journal-article","created":{"date-parts":[[2006,9,2]],"date-time":"2006-09-02T01:03:43Z","timestamp":1157159023000},"page":"2658-2666","source":"Crossref","is-referenced-by-count":25,"title":["A locally adaptive statistical procedure (LAP) to identify differentially expressed chromosomal regions"],"prefix":"10.1093","volume":"22","author":[{"given":"A.","family":"Callegaro","sequence":"first","affiliation":[{"name":"Department of Chemical Process Engineering, University of Padua \u00a0 Via Marzolo 9, I-35131 Padua, Italy"}]},{"given":"D.","family":"Basso","sequence":"additional","affiliation":[{"name":"Department of Chemical Process Engineering, University of Padua \u00a0 Via Marzolo 9, I-35131 Padua, Italy"}]},{"given":"S.","family":"Bicciato","sequence":"additional","affiliation":[{"name":"Department of Chemical Process Engineering, University of Padua \u00a0 Via Marzolo 9, I-35131 Padua, Italy"}]}],"member":"286","published-online":{"date-parts":[[2006,9,1]]},"reference":[{"key":"2023012408422997800_b1","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1126\/science.1056794","article-title":"The human transcriptome map: clustering of highly expressed genes in chromosomal domains","volume":"291","author":"Caron","year":"2001","journal-title":"Science"},{"key":"2023012408422997800_b2","article-title":"Integration of whole-genome SNP mapping and transcriptional data in the human metastatic renal carcinoma Caki-1 cell line","author":"Cifola","year":"2006","journal-title":"BMC Genomics"},{"key":"2023012408422997800_b3","doi-asserted-by":"crossref","first-page":"RESEARCH0075","DOI":"10.1186\/gb-2002-3-12-research0075","article-title":"Identification of frequent cytogenetic aberrations in hepatocellular carcinoma using gene-expression microarray data","volume":"3","author":"Crawley","year":"2002","journal-title":"Genome Biol."},{"key":"2023012408422997800_b4","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1038\/sj.onc.1207345","article-title":"Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis","volume":"23","author":"Cromer","year":"2004","journal-title":"Oncogene"},{"key":"2023012408422997800_b5","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1158\/0008-5472.CAN-04-0534","article-title":"Robust classification of renal cell carcinoma based on gene expression data and predicted cytogenetic profiles","volume":"64","author":"Furge","year":"2004","journal-title":"Cancer Res."},{"key":"2023012408422997800_b6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/10618600.1997.10474726","article-title":"Local bandwidth choice in kernel regression estimation","volume":"6","author":"Herrmann","year":"1997","journal-title":"J. Graphic. Comput. Statist."},{"key":"2023012408422997800_b7","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1038\/sj.onc.1208383","article-title":"Microarray analyses reveal strong influence of DNA copy number alterations on the transcriptional patterns in pancreatic cancer: implications for the interpretation of genomic amplifications","volume":"24","author":"Heidenblad","year":"2005","journal-title":"Oncogene"},{"key":"2023012408422997800_b8","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1093\/bioinformatics\/btg314","article-title":"Combining DNA expression with positional information to detect functional silencing of chromosomal regions","volume":"19","author":"Husing","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012408422997800_b9","first-page":"6240","article-title":"Impact of DNA amplification on gene expression patterns in breast cancer","volume":"62","author":"Hyman","year":"2002","journal-title":"Cancer Res."},{"key":"2023012408422997800_b10","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/ana.20607","article-title":"Two types of chromosome 1p losses with opposite significance in gliomas","volume":"58","author":"Idbaih","year":"2005","journal-title":"Ann. Neurol."},{"key":"2023012408422997800_b11","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/10618600.1996.10474713","article-title":"R: a language for data analysis and graphics","volume":"5","author":"Ihaka","year":"1996","journal-title":"J. Comput. Graphic. Statist."},{"key":"2023012408422997800_b12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1152\/physiolgenomics.00116.2002","article-title":"Expression imbalance map: a new visualization method for detection of mRNA expression imbalance regions","volume":"13","author":"Kano","year":"2003","journal-title":"Physiol. Genomics"},{"key":"2023012408422997800_b13","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1093\/hmg\/ddg251","article-title":"A unification of mosaic structures in the human genome","volume":"12","author":"Lercher","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"2023012408422997800_b14","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/bioinformatics\/bti417","article-title":"A model-based scan statistic for identifying extreme chromosomal regions of gene expression in human tumors","volume":"21","author":"Levin","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012408422997800_b15","doi-asserted-by":"crossref","first-page":"9197","DOI":"10.1073\/pnas.161272798","article-title":"Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression","volume":"98","author":"Lu","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408422997800_b16","doi-asserted-by":"crossref","first-page":"8715","DOI":"10.1073\/pnas.0400027101","article-title":"Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant progression","volume":"101","author":"Masayesva","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408422997800_b17","doi-asserted-by":"crossref","first-page":"7263","DOI":"10.1158\/0008-5472.CAN-04-1275","article-title":"Distinct chromosomal bias of gene expression signatures in the progression of hepatocellular carcinoma","volume":"64","author":"Midorikawa","year":"2004","journal-title":"Cancer Res."},{"key":"2023012408422997800_b18","first-page":"1602","article-title":"Gene expression-based classification of malignant gliomas correlates better with survival than histological classification","volume":"63","author":"Nutt","year":"2003","journal-title":"Cancer Res."},{"key":"2023012408422997800_b19","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/gcc.20133","article-title":"Formation of der(19)t(1;19)(q23;p13) in acute lymphoblastic leukemia","volume":"42","author":"Paulsson","year":"2005","journal-title":"Genes Chromosomes Cancer"},{"key":"2023012408422997800_b20","doi-asserted-by":"crossref","first-page":"12963","DOI":"10.1073\/pnas.162471999","article-title":"Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors","volume":"99","author":"Pollack","year":"2002","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408422997800_b21","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1158\/0008-5472.CAN-04-2706","article-title":"Visualizing chromosomes as transcriptome correlation maps: evidence of chromosomal domains containing co-expressed genes\u2014a study of 130 invasive ductal breast carcinomas","volume":"65","author":"Reyal","year":"2005","journal-title":"Cancer Res."},{"key":"2023012408422997800_b22","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1182\/blood-2003-01-0338","article-title":"Classification of pediatric acute lymphoblastic leukemia by gene expression profiling","volume":"102","author":"Ross","year":"2003","journal-title":"Blood"},{"key":"2023012408422997800_b23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/jnen\/61.1.58","article-title":"Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade \u2018oligodendroglioma\u2019","volume":"61","author":"Sasaki","year":"2002","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2023012408422997800_b24","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genome-wide experiments","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408422997800_b25","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1093\/bioinformatics\/bti183","article-title":"MACAT\u2014microarray chromosome analysis tool","volume":"21","author":"Toedling","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012408422997800_b26","doi-asserted-by":"crossref","first-page":"5116","DOI":"10.1073\/pnas.091062498","article-title":"Significance analysis of microarrays applied to the ionizing radiation response","volume":"98","author":"Tusher","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408422997800_b27","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1101\/gr.1649303","article-title":"The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes","volume":"13","author":"Versteeg","year":"2003","journal-title":"Genome Res."},{"key":"2023012408422997800_b28","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1073\/pnas.98.3.1124","article-title":"Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics","volume":"98","author":"Virtaneva","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408422997800_b29","first-page":"5781","article-title":"Genome-wide identification of chromosomal regions of increased tumor expression by transcriptome analysis","volume":"63","author":"Zhou","year":"2003","journal-title":"Cancer Res."},{"key":"2023012408422997800_b30","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1136\/jmg.2004.025353","article-title":"Identification of discrete chromosomal deletion by binary recursive partitioning of microarray differential expression data","volume":"42","author":"Zhou","year":"2005","journal-title":"J. Med. Genet."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/21\/2658\/48838319\/bioinformatics_22_21_2658.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/21\/2658\/48838319\/bioinformatics_22_21_2658.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T18:59:48Z","timestamp":1736535588000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/22\/21\/2658\/252091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,1]]},"references-count":30,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2006,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btl455","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"type":"electronic","value":"1367-4811"},{"type":"print","value":"1367-4803"}],"subject":[],"published-other":{"date-parts":[[2006,11,1]]},"published":{"date-parts":[[2006,9,1]]}}}