SUM: a new way to incorporate mismatch probe measurements

Affymetrix's high-density oligonucleotide arrays offer an exciting technology in biomedical research. With more and more statistical involvement in every step of the process, there has been a constant effort to make sure that the expression data are appropriately extracted in the first place. According to Affymetrix GeneChip technology, each gene is represented by 11-20 oligo probe pairs; the challenge is how to extract one meaningful number, expression, from the 11-20 pairs of numbers. More specifically, there is first a need to differentiate the components of specific binding, nonspecific binding, and optical background noise in both PM and MM probes, and then an expression measure that is proportional to the true abundance of transcripts is to be derived. A new method, SUM, which sums up PM and MM values and then follows a process similar to that of RMA, is considered. The performance of SUM is investigated and compared to the three most popular methods, MAS5, Whip, and RMA. The assessments are based on a well-controlled experiment dataset that is publicly available. The results show that in several respects the performance of SUM is comparable to that of RMA and Whip, and all three of these methods show some advantages over MAS5. There is some evidence showing that SUM has higher differential sensitivity than other methods in certain situations. (C) 2004 Elsevier Inc. All rights reserved.