A New Normalizing Algorithm for BAC CGH Arrays with Quality Control Metrics

[摘要] The main focus in pin-tip (or print-tip) microarray analysis is determining which probes, genes, or oligonucleotidesare differentially expressed. Specifically in array comparative genomic hybridization (aCGH) experiments,researchers search for chromosomal imbalances in the genome. To model this data, scientists apply statistical methodsto the structure of the experiment and assume that the data consist of the signal plus random noise. In thispaper we propose “SmoothArray”, a new method to preprocess comparative genomic hybridization (CGH)bacterial artificial chromosome (BAC) arrays and we show the effects on a cancer dataset. As part of our R softwarepackage “aCGHplus,” this freely available algorithm removes the variation due to the intensity effects, pin/print-tip,the spatial location on the microarray chip, and the relative location from the well plate. removal of this variationimproves the downstream analysis and subsequent inferences made on the data. Further, we present measures toevaluate the quality of the dataset according to the arrayer pins, 384-well plates, plate rows, and plate columns. Wecompare our method against competing methods using several metrics to measure the biological signal. With thisnovel normalization algorithm and quality control measures, the user can improve their inferences on datasets andpinpoint problems that may arise in their BAC aCGH technology.

[学科分类] 基础医学