Outcome signature genes in breast cancer: is there a unique set? Export

@article{citeulike:78312, abstract = {MOTIVATION: Predicting the metastatic potential of primary malignant tissues has direct bearing on the choice of therapy. Several microarray studies yielded gene sets whose expression profiles successfully predicted survival. Nevertheless, the overlap between these gene sets is almost zero. Such small overlaps were observed also in other complex diseases, and the variables that could account for the differences had evoked a wide interest. One of the main open questions in this context is whether the disparity can be attributed only to trivial reasons such as different technologies, different patients and different types of analyses. RESULTS: To answer this question, we concentrated on a single breast cancer dataset, and analyzed it by a single method, the one which was used by van't Veer et al. to produce a set of outcome-predictive genes. We showed that, in fact, the resulting set of genes is not unique; it is strongly influenced by the subset of patients used for gene selection. Many equally predictive lists could have been produced from the same analysis. Three main properties of the data explain this sensitivity: (1) many genes are correlated with survival; (2) the differences between these correlations are small; (3) the correlations fluctuate strongly when measured over different subsets of patients. A possible biological explanation for these properties is discussed. CONTACT: eytan.domany@weizmann.ac.il SUPPLEMENTARY INFORMATION: http://www.weizmann.ac.il/physics/complex/compphys/downloads/liate/}, author = {Ein-Dor, Liat and Kela, Itai and Domany, Eytan}, citeulike-article-id = {78312}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/bioinformatics/bth469}, citeulike-linkout-1 = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/21/2/171}, citeulike-linkout-2 = {http://www.ingentaconnect.com/content/oup/cabios/2005/00000021/00000002/art00171}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15308542}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15308542}, day = {15}, doi = {10.1093/bioinformatics/bth469}, issn = {1367-4803}, journal = {Bioinformatics (Oxford, England)}, keywords = {70-gene, 76-gene, amsterdam, breast-cancer, rotterdam, signature}, month = {January}, number = {2}, pages = {171--178}, posted-at = {2008-03-27 12:00:14}, priority = {2}, publisher = {Oxford University Press}, title = {Outcome signature genes in breast cancer: is there a unique set?}, url = {http://dx.doi.org/10.1093/bioinformatics/bth469}, volume = {21}, year = {2005} }

TY - JOUR ID - citeulike:78312 L3 - citeulike-article-id:78312 N2 - MOTIVATION: Predicting the metastatic potential of primary malignant tissues has direct bearing on the choice of therapy. Several microarray studies yielded gene sets whose expression profiles successfully predicted survival. Nevertheless, the overlap between these gene sets is almost zero. Such small overlaps were observed also in other complex diseases, and the variables that could account for the differences had evoked a wide interest. One of the main open questions in this context is whether the disparity can be attributed only to trivial reasons such as different technologies, different patients and different types of analyses. RESULTS: To answer this question, we concentrated on a single breast cancer dataset, and analyzed it by a single method, the one which was used by van't Veer et al. to produce a set of outcome-predictive genes. We showed that, in fact, the resulting set of genes is not unique; it is strongly influenced by the subset of patients used for gene selection. Many equally predictive lists could have been produced from the same analysis. Three main properties of the data explain this sensitivity: (1) many genes are correlated with survival; (2) the differences between these correlations are small; (3) the correlations fluctuate strongly when measured over different subsets of patients. A possible biological explanation for these properties is discussed. CONTACT: eytan.domany@weizmann.ac.il SUPPLEMENTARY INFORMATION: http://www.weizmann.ac.il/physics/complex/compphys/downloads/liate/ IS - 2 JF - Bioinformatics (Oxford, England) SN - 1367-4803 EP - 178 TI - Outcome signature genes in breast cancer: is there a unique set? PB - Oxford University Press VL - 21 SP - 171 KW - 70-gene KW - 76-gene KW - amsterdam KW - breast-cancer KW - rotterdam KW - signature AU - Ein-Dor, Liat AU - Kela, Itai AU - Domany, Eytan PY - 2005/01/15/ UR - http://dx.doi.org/10.1093/bioinformatics/bth469 ER -