BMC Bioinformatics · 2018 · 122 citations · 28 references
Life SciencesBiologyBiostatisticsEpidemiologic MethodsGenomic Data AnalysisGenomicsBatch Effect CorrectionNext-generation SequencingBatch Effect DetectionBatch Effect ModelingBatch Effect RobustnessGenomic BiomarkersSample Size EstimationStatistical Power AnalysisStatistical Power Estimation
BACKGROUND: Combining genomic data sets from multiple studies is advantageous to increase statistical power in studies where logistical considerations restrict sample size or require the sequential generation of data. However, significant technical heterogeneity is commonly observed across multiple batches of data that are generated from different processing or reagent batches, experimenters, protocols, or profiling platforms. These so-called batch effects often confound true biological relationships in the data, reducing the power benefits of combining multiple batches, and may even lead to spurious results in some combined studies. Therefore there is significant need for effective methods and software tools that account for batch effects in high-throughput genomic studies. RESULTS: Here we contribute multiple methods and software tools for improved combination and analysis of data from multiple batches. In particular, we provide batch effect solutions for cases where the severity of the batch effects is not extreme, and for cases where one high-quality batch can serve as a reference, such as the training set in a biomarker study. We illustrate our approaches and software in both simulated and real data scenarios. CONCLUSIONS: We demonstrate the value of these new contributions compared to currently established approaches in the specified batch correction situations.
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Comprehensive molecular portraits of human breast tumours