Abstract
BackgroundHigh-throughput technology could generate thousands to millions biomarker measurements in one experiment. However, results from high throughput analysis are often barely reproducible due to small sample size. Different statistical methods have been proposed to tackle this “small n and large p” scenario, for example different datasets could be pooled or integrated together to provide an effective way to improve reproducibility. However, the raw data is either unavailable or hard to integrate due to different experimental conditions, thus there is an emerging need to develop a method for “knowledge integration” in high-throughput data analysis.ResultsIn this study, we proposed an integrative prescreening approach, SKI, for high-throughput data analysis. A new rank is generated based on two initial ranks: (1) knowledge based rank; and (2) marginal correlation based rank. Our simulation shows the SKI outperforms other methods without knowledge-integration in terms of higher true positive rate given the same number of variables selected. We also applied our method in a drug response study and found its performance to be better than regular screening methods.ConclusionThe proposed method provides an effective way to integrate knowledge for high-throughput analysis. It could easily implemented with our provided R package named SKI.
Highlights
High-throughput technology could generate thousands to millions biomarker measurements in one experiment
In genome-wide association studies (GWAS), single nucleotide polymorphisms (SNPs) are screened site-by-site to test the association between diseases and complex traits
The goal of this study is to develop a general procedure for variable selection with knowledge integration
Summary
High-throughput technology could generate thousands to millions biomarker measurements in one experiment. Results from high throughput analysis are often barely reproducible due to small sample size. The raw data is either unavailable or hard to integrate due to different experimental conditions, there is an emerging need to develop a method for “knowledge integration” in high-throughput data analysis. As large numbers of biomarkers can be measured simultaneously at a relative small cost, the bottleneck for such omics studies has become the expansion of the number of samples collected. In genome-wide association studies (GWAS), single nucleotide polymorphisms (SNPs) are screened site-by-site to test the association between diseases and complex traits. This approach ignores the underlying correlation structure between genomic markers, leading to the absence of
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