Comparison of CNV-level and marker-level tests for the Gemcitabine data.

<p>number of CNV calls in that region. If , no association test was carried out, hence the blank entries. For the marker-level tests, a FWER of 0.01–0.05 means that controlling the FWER at the level, we obtain a segmentation in this region, but that if we control the FWER at the level, we do not.</p

Effect of CNV-calling threshold () on the power to detect a CNV.

<p>Continuous outcome, 10,000 replications per cell, CNV size = 30 markers).</p

Example of LRR data for a putative CNV on Chromosome 3 for a cell line in the gemcitabine study.

<p>The gray region denotes the estimated boundary of the CNV. The points in the gray region have a mean LRR of −0.98; the surrounding points have a mean of −0.11.</p

Plot of from Gemcitabine marker-level tests as a function of position along the chromosome.

<p>The shaded region denotes a region of significant elevation, as detected by the methods described in “Marker-level testing”. The top of the plot contains annotations describing the results of the CNV-level analysis in three distinct regions. is the mean adjusted IC50 for cell lines with a called CNV in that region; is the mean adjusted IC50 for cell lines without a called CNV in that region.</p

Effect of various transformations of -value prior to application of CBS on the power to detect a CNV.

<p>Continuous outcome, 10,000 replications per cell, CNV size = 30 markers. “Power” here refers to the probability that a segment in which low -values have aggregated can be separated from the test results from surrounding markers. The “no pooling” analysis (which implements a Bonferroni correction to maintain the correct overall type I error rate) is included to illustrate the power gained by pooling information across nearby markers.</p

Power as a function of method and CNV size.

<p>The CNV-level testing approach uses a false positive CNV call rate of 0.01; the marker-level approach uses the probit transformation. The lower dashed line represents the type I error rate, while the upper dashed line represents the “oracle” power that would be possible if the true CNV status were known, with no measurement error.</p

Illustration of marker-level testing.

<p><i>Top:</i> Marker-level tests at three markers for the gemcitabine study. The phenotype (IC50, a continuous outcome described in “Gemcitabine pharmacogenomic study”) is plotted as a function of LRR, along with the regression line. The -values for the three -tests are, respectively, from left to right. 0.25, 0.0008, and 0.0008, respectively, from left to right. <i>Bottom:</i> Plot of from the marker-level tests as a function of position along the chromosome. The three tests from the top part of the figure are plotted in red.</p

Example of LRR data for a simulated CNV.

<p><i>Left:</i> The noise, randomly drawn from among the observed measurement errors for a single subject. <i>Middle:</i> The spiked-in signal. <i>Right:</i> The resulting simulated data, which looks qualitatively similar to the real CNV in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034262#pone-0034262-g001" target="_blank">Figure 1</a>.</p

Supplementary Data from Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study

Supplementary Tables 1-3</p

Supplementary Figures and Tables from Randomized Phase IIB Trial of the Lignan Secoisolariciresinol Diglucoside in Premenopausal Women at Increased Risk for Development of Breast Cancer

Supplementary Figures and Tables</p