A statistical normalization method and differential expression analysis for RNA-seq data between different species

Yan Zhou, Jiadi Zhu, Tiejun TONG, Junhui Wang, Bingqing Lin, Jun Zhang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

19 Citations (Scopus)


Background: High-throughput techniques bring novel tools and 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, normalization 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 by using the 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", which is freely available at http://www.bioconductor.org/packages/devel/bioc/html/SCBN.html.

Original languageEnglish
Article number163
JournalBMC Bioinformatics
Issue number1
Publication statusPublished - 29 Mar 2019

Scopus Subject Areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

User-Defined Keywords

  • Differential expression
  • Hypothesis test
  • Normalization
  • Orthologous genes
  • RNA-seq


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