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Updated: Aug 13, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
Published on: June 23, 2012
Getting more from digital SNP data
Noureddine El Karoui1, Wei Zhou, Alice S Whittemore
1Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
The digital SNP method has been proposed for identifying loss of heterozygosity (LOH) in tumour tissue and correlating it with patients' clinical characteristics. The method evaluates a tumour's allelic count at a single nucleotide polymorphism (SNP) for which the patient's normal tissue is heterozygous. The count is used to classify the tumour as positive or negative for LOH, using the sequential probability ratio test (SPRT). However, the SPRT was not developed for analysing digital SNP experiments. When applied to digital SNP data, the SPRT has several anomalies that can result in both loss of data and tumour misclassification. The anomalies are caused by discrepancies between the design of digital SNP experiments and the setting for which SPRT was developed. We propose an alternative classification scheme based on the false discovery rate, and show that it outperforms the SPRT when applied to Digital SNP data.
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