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Pooling breast cancer datasets has a synergetic effect on classification performance and improves signature stability.

ABSTRACT: BACKGROUND: Michiels et al. (Lancet 2005; 365: 488-92) employed a resampling strategy to show that the genes identified as predictors of prognosis from resamplings of a single gene expression dataset are highly variable. The genes most frequently identified in the separate resamplings were put forward as a 'gold standard'. On a higher level, breast cancer datasets collected by different institutions can be considered as resamplings from the underlying breast cancer population. The limited overlap between published prognostic signatures confirms the trend of signature instability identified by the resampling strategy. Six breast cancer datasets, totaling 947 samples, all measured on the Affymetrix platform, are currently available. This provides a unique opportunity to employ a substantial dataset to investigate the effects of pooling datasets on classifier accuracy, signature stability and enrichment of functional categories. RESULTS: We show that the resampling strategy produces a suboptimal ranking of genes, which can not be considered to be a 'gold standard'. When pooling breast cancer datasets, we observed a synergetic effect on the classification performance in 73% of the cases. We also observe a significant positive correlation between the number of datasets that is pooled, the validation performance, the number of genes selected, and the enrichment of specific functional categories. In addition, we have evaluated the support for five explanations that have been postulated for the limited overlap of signatures. CONCLUSION: The limited overlap of current signature genes can be attributed to small sample size. Pooling datasets results in more accurate classification and a convergence of signature genes. We therefore advocate the analysis of new data within the context of a compendium, rather than analysis in isolation.

SUBMITTER: van Vliet MH

PROVIDER: S-EPMC2527336 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Pooling breast cancer datasets has a synergetic effect on classification performance and improves signature stability.

van Vliet Martin H MH Reyal Fabien F Horlings Hugo M HM van de Vijver Marc J MJ Reinders Marcel J T MJ Wessels Lodewyk F A LF

BMC genomics 20080806

<h4>Background</h4>Michiels et al. (Lancet 2005; 365: 488-92) employed a resampling strategy to show that the genes identified as predictors of prognosis from resamplings of a single gene expression dataset are highly variable. The genes most frequently identified in the separate resamplings were put forward as a 'gold standard'. On a higher level, breast cancer datasets collected by different institutions can be considered as resamplings from the underlying breast cancer population. The limited ...[more]

PMID: 18684329

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Project description:Breast cancer is the second most frequent cancer worldwide, following lung cancer and the fifth leading cause of cancer death and a major cause of cancer death among women. In recent years, convolutional neural networks (CNNs) have been successfully applied for the diagnosis of breast cancer using different imaging modalities. Pooling is a main data processing step in CNN that decreases the feature maps' dimensionality without losing major patterns. However, the effect of pooling layer was not studied efficiently in literature. In this paper, we propose a novel design for the pooling layer called vector pooling block (VPB) for the CCN algorithm. The proposed VPB consists of two data pathways, which focus on extracting features along horizontal and vertical orientations. The VPB makes the CNNs able to collect both global and local features by including long and narrow pooling kernels, which is different from the traditional pooling layer, that gathers features from a fixed square kernel. Based on the novel VPB, we proposed a new pooling module called AVG-MAX VPB. It can collect informative features by using two types of pooling techniques, maximum and average pooling. The VPB and the AVG-MAX VPB are plugged into the backbone CNNs networks, such as U-Net, AlexNet, ResNet18 and GoogleNet, to show the advantages in segmentation and classification tasks associated with breast cancer diagnosis from thermograms. The proposed pooling layer was evaluated using a benchmark thermogram database (DMR-IR) and its results compared with U-Net results which was used as base results. The U-Net results were as follows: global accuracy = 96.6%, mean accuracy = 96.5%, mean IoU = 92.07%, and mean BF score = 78.34%. The VBP-based results were as follows: global accuracy = 98.3%, mean accuracy = 97.9%, mean IoU = 95.87%, and mean BF score = 88.68% while the AVG-MAX VPB-based results were as follows: global accuracy = 99.2%, mean accuracy = 98.97%, mean IoU = 98.03%, and mean BF score = 94.29%. Other network architectures also demonstrate superior improvement considering the use of VPB and AVG-MAX VPB.

Project description:BackgroundOne of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively.Methods and findingsOur results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER- patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome.ConclusionsThe 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic value for both ER-positive and ER-negative breast cancer. The signature was selected using a novel biological approach and hence holds promise to represent the key biological processes of breast cancer.

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Pooling breast cancer datasets has a synergetic effect on classification performance and improves signature stability.

Publications

Pooling breast cancer datasets has a synergetic effect on classification performance and improves signature stability.

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