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Background: High-throughput techniques bring novel tools but also statistical challenges to genomic research. Identifying genes with differential expression between different species is an effective way to discover evolutionarily conserved transcriptional responses. To remove systematic variation between different species for a fair comparison, the normalization procedure serves as a crucial pre-processing step that adjusts for the varying sample sequencing depths and other confounding technical effects. Results: In this paper, we propose a scale based normalization (SCBN) method by taking into account the available knowledge of conserved orthologous genes and hypothesis testing framework. Considering the different gene lengths and unmapped genes between different species, we formulate the problem from the perspective of hypothesis testing and search for the optimal scaling factor that minimizes the deviation between the empirical and nominal type I errors. Conclusions: Simulation studies show that the proposed method performs significantly better than the existing competitor in a wide range of settings. An RNA-seq dataset of different species is also analyzed and it coincides with the conclusion that the proposed method outperforms the existing method. For practical applications, we have also developed an R package named SCBN and the software is available at http://www.bioconductor.org/packages/devel/bioc/html/SCBN.html.
Background: Since the invention of next-generation RNA sequencing (RNA-seq) technologies, they have become a powerful tool to study the presence and quantity of RNA molecules in biological samples and have revolutionized transcriptomic studies. The a
Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequentl
It is largely taken for granted that differential abundance analysis is, by default, the best first step when analyzing genomic data. We argue that this is not necessarily the case. In this article, we identify key limitations that are intrinsic to d
Chemical mapping methods probe RNA structure by revealing and leveraging correlations of a nucleotides structural accessibility or flexibility with its reactivity to various chemical probes. Pioneering work by Lucks and colleagues has expanded this m
Next-generation RNA sequencing (RNA-seq) technology has been widely used to assess full-length RNA isoform abundance in a high-throughput manner. RNA-seq data offer insight into gene expression levels and transcriptome structures, enabling us to bett