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A promising alternative is to base prediction entirely upon the relative expression ordering of a small number of genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We present a three-gene version of \"relative expression analysis\" (<jats:italic>RXA<\/jats:italic>), a rigorous and systematic comparison with earlier approaches in a variety of cancer studies, a clinically relevant application to predicting germline BRCA1 mutations in breast cancer and a cross-study validation for predicting ER status. In the BRCA1 study,<jats:italic>RXA<\/jats:italic>yields high accuracy with a simple decision rule: in tumors carrying mutations, the expression of a \"reference gene\" falls between the expression of two differentially expressed genes,<jats:italic>PPP1CB<\/jats:italic>and<jats:italic>RNF14<\/jats:italic>. An analysis of the protein-protein interactions among the triplet of genes and<jats:italic>BRCA<\/jats:italic>1 suggests that the classifier has a biological foundation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>RXA<\/jats:italic>has the potential to identify genomic \"marker interactions\" with plausible biological interpretation and direct clinical applicability. It provides a general framework for understanding the roles of the genes involved in decision rules, as illustrated for the difficult and clinically relevant problem of identifying<jats:italic>BRCA<\/jats:italic>1 mutation carriers.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-10-256","type":"journal-article","created":{"date-parts":[[2009,8,21]],"date-time":"2009-08-21T06:13:25Z","timestamp":1250835205000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The ordering of expression among a few genes can provide simple cancer biomarkers and signal BRCA1 mutations"],"prefix":"10.1186","volume":"10","author":[{"given":"Xue","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahman","family":"Afsari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Marchionni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Cope","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Parmigiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Naiman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald","family":"Geman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,8,20]]},"reference":[{"issue":"5","key":"2986_CR1","doi-asserted-by":"publisher","first-page":"358","DOI":"10.7326\/0003-4819-148-5-200803040-00208","volume":"148","author":"L Marchionni","year":"2008","unstructured":"Marchionni L, Wilson RF, Wolff AC, Marinopoulos S, Parmigiani G, Bass EB, Goodman SN: Systematic review: gene expression profiling assays in early-stage breast cancer. 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