{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:00:20Z","timestamp":1783976420835,"version":"3.55.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Cellular heterogeneity is present in almost all gene expression profiles. However, transcriptome analysis of tissue specimens often ignores the cellular heterogeneity present in these samples. Standard deconvolution algorithms require prior knowledge of the cell type frequencies within a tissue or their in vitro expression profiles. Furthermore, these algorithms tend to report biased estimations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Here, we describe a Digital Sorting Algorithm (DSA) for extracting cell-type specific gene expression profiles from mixed tissue samples that is unbiased and does not require prior knowledge of cell type frequencies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The results suggest that DSA is a specific and sensitivity algorithm in gene expression profile deconvolution and will be useful in studying individual cell types of complex tissues.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-14-89","type":"journal-article","created":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T21:30:42Z","timestamp":1362691842000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":196,"title":["Digital sorting of complex tissues for cell type-specific gene expression profiles"],"prefix":"10.1186","volume":"14","author":[{"given":"Yi","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Wooi","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifang","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel ML","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhandong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"5794_CR1","doi-asserted-by":"publisher","first-page":"4801","DOI":"10.1073\/pnas.0409768102","volume":"102","author":"JP Cobb","year":"2005","unstructured":"Cobb JP: Application of genome-wide expression analysis to human health and disease. Proc Natl Acad Sci 2005, 102: 4801-4806. 10.1073\/pnas.0409768102","journal-title":"Proc Natl Acad Sci"},{"key":"5794_CR2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1471-2105-11-27","volume":"11","author":"D Repsilber","year":"2010","unstructured":"Repsilber D, Kern S, Telaar A, Walzl G, Black GF, Selbig J, Parida SK, Kaufmann SH, Jacobsen M: Biomarker discovery in heterogeneous tissue samples -taking the in-silico deconfounding approach. BMC Bioinformatics 2010, 11: 27. 10.1186\/1471-2105-11-27","journal-title":"BMC Bioinformatics"},{"key":"5794_CR3","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/1471-2164-7-115","volume":"7","author":"C Palmer","year":"2006","unstructured":"Palmer C, Diehn M, Alizadeh AA, Brown PO: BMC Genomics. 2006, 7: 115. 10.1186\/1471-2164-7-115","journal-title":"BMC Genomics"},{"key":"5794_CR4","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144: 646-674. 10.1016\/j.cell.2011.02.013","journal-title":"Cell"},{"key":"5794_CR5","doi-asserted-by":"publisher","first-page":"8887","DOI":"10.1158\/0008-5472.CAN-05-1702","volume":"65","author":"F Yang","year":"2005","unstructured":"Yang F: Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res 2005, 65: 8887-8895. 10.1158\/0008-5472.CAN-05-1702","journal-title":"Cancer Res"},{"key":"5794_CR6","first-page":"2912","volume":"8","author":"JA Tuxhorn","year":"2002","unstructured":"Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR: Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 2002, 8: 2912-2923.","journal-title":"Clin Cancer Res"},{"key":"5794_CR7","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/nrc2618","volume":"9","author":"JA Joyce","year":"2008","unstructured":"Joyce JA, Pollard JW: Microenvironmental regulation of metastasis. Nat Rev Cancer 2008, 9: 239-252. 10.1038\/nrg2317","journal-title":"Nat Rev Cancer"},{"key":"5794_CR8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nri1995","volume":"7","author":"H Yu","year":"2007","unstructured":"Yu H, Kortylewski M, Pardoll D: Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007, 7: 41-51. 10.1038\/nri1995","journal-title":"Nat Rev Immunol"},{"key":"5794_CR9","doi-asserted-by":"publisher","first-page":"e20267","DOI":"10.1371\/journal.pone.0020267","volume":"6","author":"VS Salsman","year":"2011","unstructured":"Salsman VS, Chow KKH, Shaffer DR, Kadikoy H, Li X-N, Gerken C, Perlaky L, Metelitsa LS, Gao X, Bhattacharjee M, Hirschi K, Heslop HE, Gottschalk S, Ahmed N: Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironment. PLoS One 2011, 6: e20267. 10.1371\/journal.pone.0020267","journal-title":"PLoS One"},{"key":"5794_CR10","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nature10138","volume":"475","author":"B-Z Qian","year":"2011","unstructured":"Qian B-Z, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW: CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 2011, 475: 222-225. 10.1038\/nature10138","journal-title":"Nature"},{"key":"5794_CR11","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1593\/neo.07871","volume":"10","author":"JC Pahler","year":"2008","unstructured":"Pahler JC, Tazzyman S, Erez N, Chen Y-Y, Murdoch C, Nozawa H, Lewis CE, Hanahan D: Plasticity in tumor-promoting inflammation: impairment of macrophage recruitment evokes a compensatory neutrophil response. Neoplasia (New York, NY) 2008, 10: 329-340.","journal-title":"Neoplasia (New York, NY)"},{"key":"5794_CR12","doi-asserted-by":"publisher","first-page":"e16493","DOI":"10.1371\/journal.pone.0016493","volume":"6","author":"BW Okaty","year":"2011","unstructured":"Okaty BW, Sugino K, Nelson SB: A quantitative comparison of cell-type-specific microarray gene expression profiling methods in the mouse brain. PLoS One 2011, 6: e16493. 10.1371\/journal.pone.0016493","journal-title":"PLoS One"},{"key":"5794_CR13","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s11060-007-9480-6","volume":"86","author":"DB Hoelzinger","year":"2007","unstructured":"Hoelzinger DB, Nakada M, Demuth T, Rosensteel T, Reavie LB, Berens ME: Autotaxin: a secreted autocrine\/paracrine factor that promotes glioma invasion. J Neurooncol 2007, 86: 297-309.","journal-title":"J Neurooncol"},{"key":"5794_CR14","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1093\/bioinformatics\/btp378","volume":"25","author":"G Quon","year":"2009","unstructured":"Quon G, Morris Q: ISOLATE: a computational strategy for identifying the primary origin of cancers using high-throughput sequencing. Bioinformatics 2009, 25: 2882-2889. 10.1093\/bioinformatics\/btp378","journal-title":"Bioinformatics"},{"key":"5794_CR15","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/1471-2105-11-42","volume":"11","author":"R Schwartz","year":"2010","unstructured":"Schwartz R, Shackney SE: Applying unmixing to gene expression data for tumor phylogeny inference. BMC Bioinformatics 2010, 11: 42. 10.1186\/1471-2105-11-42","journal-title":"BMC Bioinformatics"},{"key":"5794_CR16","doi-asserted-by":"publisher","first-page":"e1002838","DOI":"10.1371\/journal.pcbi.1002838","volume":"8","author":"W Qiao","year":"2012","unstructured":"Qiao W, Quon G, Csaszar E, Yu M, Morris Q, Zandstra PW: PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions. PLoS Comput Biol 2012, 8: e1002838. 10.1371\/journal.pcbi.1002838","journal-title":"PLoS Comput Biol"},{"key":"5794_CR17","doi-asserted-by":"publisher","first-page":"10370","DOI":"10.1073\/pnas.1832361100","volume":"100","author":"P Lu","year":"2003","unstructured":"Lu P: Expression deconvolution: a reinterpretation of DNA microarray data reveals dynamic changes in cell populations. Proc Natl Acad Sci 2003, 100: 10370-10375. 10.1073\/pnas.1832361100","journal-title":"Proc Natl Acad Sci"},{"key":"5794_CR18","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1186\/1471-2105-7-328","volume":"7","author":"M Wang","year":"2006","unstructured":"Wang M, Master SR, Chodosh LA: BMC Bioinformatics. 2006, 7: 328. 10.1186\/1471-2105-7-328","journal-title":"BMC Bioinformatics"},{"key":"5794_CR19","doi-asserted-by":"publisher","first-page":"e6098","DOI":"10.1371\/journal.pone.0006098","volume":"4","author":"AR Abbas","year":"2009","unstructured":"Abbas AR, Wolslegel K, Seshasayee D, Modrusan Z, Clark HF: Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus. PLoS One 2009, 4: e6098. 10.1371\/journal.pone.0006098","journal-title":"PLoS One"},{"key":"5794_CR20","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/nmeth.1439","volume":"7","author":"SS Shen-Orr","year":"2010","unstructured":"Shen-Orr SS, Tibshirani R, Khatri P, Bodian DL, Staedtler F, Perry NM, Hastie T, Sarwal MM, Davis MM, Butte AJ: Cell type-specific gene expression differences in complex tissues. Nat Methods 2010, 7: 287-289. 10.1038\/nmeth.1439","journal-title":"Nat Methods"},{"key":"5794_CR21","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.meegid.2011.08.014","volume":"12","author":"R Gaujoux","year":"2012","unstructured":"Gaujoux R, Seoighe C: Semi-supervised nonnegative matrix factorization for gene expression deconvolution: a case study. Infect Genet Evol 2012, 12: 913-921. 10.1016\/j.meegid.2011.08.014","journal-title":"Infect Genet Evol"},{"key":"5794_CR22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/nmeth.1830","volume":"9","author":"Y Zhong","year":"2012","unstructured":"Zhong Y, Liu Z: Gene expression deconvolution in linear space. Nat Methods 2012, 9: 8-9. author reply 9 author reply 9","journal-title":"Nat Methods"},{"key":"5794_CR23","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1186\/1471-2105-9-271","volume":"9","author":"X Liu","year":"2008","unstructured":"Liu X, Yu X, Zack DJ, Zhu H, Qian J: TiGER: a database for tissue-specific gene expression and regulation. BMC Bioinformatics 2008, 9: 271. 10.1186\/1471-2105-9-271","journal-title":"BMC Bioinformatics"},{"key":"5794_CR24","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1093\/bioinformatics\/bti042","volume":"21","author":"I Yanai","year":"2005","unstructured":"Yanai I, Benjamin H, Shmoish M, Chalifa-Caspi V, Shklar M, Ophir R, Bar-Even A, Horn-Saban S, Safran M, Domany E, Lancet D, Shmueli O: Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification. Bioinformatics 2005, 21: 650-659. 10.1093\/bioinformatics\/bti042","journal-title":"Bioinformatics"},{"key":"5794_CR25","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.ygeno.2005.01.009","volume":"85","author":"J Kelley","year":"2005","unstructured":"Kelley J, de Bono B, Trowsdale J: IRIS: a database surveying known human immune system genes. Genomics 2005, 85: 503-511. 10.1016\/j.ygeno.2005.01.009","journal-title":"Genomics"},{"key":"5794_CR26","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/nmeth.1710","volume":"8","author":"A Kuhn","year":"2011","unstructured":"Kuhn A, Thu D, Waldvogel HJ, Faull RLM, Luthi-Carter R: Population-specific expression analysis (PSEA) reveals molecular changes in diseased brain. Nat Methods 2011, 8: 945-947. 10.1038\/nmeth.1710","journal-title":"Nat Methods"},{"key":"5794_CR27","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1093\/bioinformatics\/bti623","volume":"21","author":"T Sing","year":"2005","unstructured":"Sing T, Sander O, Beerenwinkel N, Lengauer T: ROCR: visualizing classifier performance in R. Bioinformatics 2005, 21: 3940-3941. 10.1093\/bioinformatics\/bti623","journal-title":"Bioinformatics"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-14-89.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T23:00:11Z","timestamp":1630537211000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-14-89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,7]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["5794"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-14-89","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,7]]},"assertion":[{"value":"13 September 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"89"}}