Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Prototypes for 4x44K PAM50 Subtyping

ABSTRACT: PAM50 intrinsic subtype classification (Parker JS, Mullins M, Cheang MCU, et al: Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes. J Clin Oncol 27:1160-1167, 2009) was used for the Z1031 patient cohort. However, to account for potential technical biases such as differences in platforms and laboratory protocols between the Z1031 data set and the PAM50 training set2, we normalized the Z1301 data set before applying the PAM50 algorithm. This is a critical step that must be taken into consideration for appropriate subtype predictions as our group and others have previously shown3,4. To appropriately normalize the Z1301 microarray data, which is entirely composed of ER-positive tumors, we needed to estimate technical bias from a cohort with equivalent subtype representation as the PAM50 training set. A set including ER-negative, HER2-positive and true normal breast samples were profiled under the same platform, protocol and laboratory (i.e. WashU) as the Z1301 data set. A total of 40 prototypic samples of the various molecular subtypes were selected to match the distribution in the PAM50 training set. The mean expression of each PAM50 gene was calculated in this set of 40. These values obtained from the prototypical sample set were used for calibration purposes and were included as a new WashU_4X44K_Calibration column in the CalibrationParameter file, which has been already provided in the PAM50 algorithm2. This adjustment step assures that each sample is placed in the appropriate ‘prototypic space’ by subtracting the calibration value of each PAM50 gene from the expression value of the corresponding gene in each tested sample. Finally, single sample predictions were performed in every Z1301 sample using the WashU_4X44K_Calibration parameter. The complete data set for the 40 prototypic arrays is submitted under GSE26082. 40 experiments were used as prototypical cases for subtype calibration purposes.

ORGANISM(S): Homo sapiens

SUBMITTER: Jeremy Hoog

PROVIDER: E-GEOD-26082 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031.

Ellis Matthew J MJ Suman Vera J VJ Hoog Jeremy J Lin Li L Snider Jacqueline J Prat Aleix A Parker Joel S JS Luo Jingqin J DeSchryver Katherine K Allred D Craig DC Esserman Laura J LJ Unzeitig Gary W GW Margenthaler Julie J Babiera Gildy V GV Marcom P Kelly PK Guenther Joseph M JM Watson Mark A MA Leitch Marilyn M Hunt Kelly K Olson John A JA

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20110509 17

<h4>Purpose</h4>Preoperative aromatase inhibitor (AI) treatment promotes breast-conserving surgery (BCS) for estrogen receptor (ER)-positive breast cancer. To study this treatment option, responses to three AIs were compared in a randomized phase II neoadjuvant trial designed to select agents for phase III investigations.<h4>Patients and methods</h4>Three hundred seventy-seven postmenopausal women with clinical stage II to III ER-positive (Allred score 6-8) breast cancer were randomly assigned t ...[more]

PMID: 21555689

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Project description:The experiment was designed to enable validation of pre-processing and test algorithms. The in-house produced cDNA-array contains 44 clones: 19 clones from mice, 4 clones from Pine (involved in photosynthesis) and 21 artificial clones from the Lucidea Universal ScoreCard (Amersham Bioscienses), where each clone was printed 480 times in 48 identically designed sub-grids. The experiment contains eight arrays with identical experimental design. Total RNA from murine cell line was divided in two samples; the reference sample was labeled with the fluorophore Cy5 and spiked with the Lucidea Universal ScoreCard reference reaction, the test sample was labeled with Cy3 and spiked with the Lucidea Universal ScoreCard test reaction. The concentrations of the Lucidea reactions are known and consequently so are the true ratios between the reference and test channels. Approximately 40% of the artificial genes were differentially expressed. The particular design of the experiment makes the data suitable for validating algorithms for pre-processing and tests for identifying differentially expressed genes. - The 80.I.1 normalization algorithm : all spots flagged as not found during image analysis considered missing values (complete filtration). Print-tip MA-loess dye normalization based on the calibration clones was applied to the raw data and the B-statistic was calculated. - The 80.II.1 normalization algorithm : all spots flagged as not found during image analysis considered missing values (complete filtration). Local background correction was applied and all spots with negative values were excluded. Print-tip MA-loess dye normalization based on the calibration clones was applied to the background corrected data and the B-statistic was calculated. - The 80.II.64 normalization algorithm : all spots flagged as not found during image analysis considered missing values (complete filtration). Local background correction was applied, negative values were excluded and all spots with a value below 64 were set to 64 (censored). Print-tip MA-loess dye normalization based on the calibration clones was applied to the background corrected data and the B-statistic was calculated. - The 80.V.1 normalization algorithm : The intensities of all spots flagged not found were treated as missing values during normalization, but prior to calculating test-statistics the spot's log-ratios were set to zero. In the special case when all arrays generated not-found spots, the gene was removed from the experiment (Partial filtration). Local background correction was applied and all negative values were considered missing values. Print-tip MA-loess dye normalization based on the calibration clones was applied to the background corrected data and the B-statistic was calculated. The experiment contains eight arrays with identical experimental design. The reference sample was labeled with the fluorophore Cy5 and spiked with the Lucidea Universal ScoreCard reference reaction, the test sample was labeled with Cy3 and spiked with the Lucidea Universal ScoreCard test reaction.

Dataset Information

Prototypes for 4x44K PAM50 Subtyping

Publications

Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031.

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