Jonckheere-Terpstra-Kendall-based non-parametric analysis of temporal differential gene expression

Hitoshi Iuchi*, Michiaki Hamada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Time-course experiments using parallel sequencers have the potential to uncover gradual changes in cells over time that cannot be observed in a two-point comparison. An essential step in time-series data analysis is the identification of temporal differentially expressed genes (TEGs) under two conditions (e.g. control versus case). Model-based approaches, which are typical TEG detection methods, often set one parameter (e.g. degree or degree of freedom) for one dataset. This approach risks modeling of linearly increasing genes with higher-order functions, or fitting of cyclic gene expression with linear functions, thereby leading to false positives/negatives. Here, we present a Jonckheere-Terpstra-Kendall (JTK)-based non-parametric algorithm for TEG detection. Benchmarks, using simulation data, show that the JTK-based approach outperforms existing methods, especially in long time-series experiments. Additionally, application of JTK in the analysis of time-series RNA-seq data from seven tissue types, across developmental stages in mouse and rat, suggested that the wave pattern contributes to the TEG identification of JTK, not the difference in expression levels. This result suggests that JTK is a suitable algorithm when focusing on expression patterns over time rather than expression levels, such as comparisons between different species. These results show that JTK is an excellent candidate for TEG detection.

Original languageEnglish
Article numberlqab021
JournalNAR Genomics and Bioinformatics
Volume3
Issue number1
DOIs
Publication statusPublished - 2021 Mar 1

ASJC Scopus subject areas

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

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