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Pathway‐based meta‐analysis for partially paired transcriptomics analysis
Author(s) -
Fung Wing Tung,
Wu Joseph T.,
Chan Wai Man Mandy,
Chan Henry H.,
Pang Herbert
Publication year - 2020
Publication title -
research synthesis methods
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.376
H-Index - 35
eISSN - 1759-2887
pISSN - 1759-2879
DOI - 10.1002/jrsm.1381
Subject(s) - transcriptome , computational biology , meta analysis , pathway analysis , computer science , replication (statistics) , bioinformatics , biology , gene , gene expression , genetics , medicine , pathology , virology
Pathway‐based differential expression analysis allows the incorporation of biological domain knowledge into transcriptomics analysis to enhance our understanding of disease mechanisms. To integrate information among multiple studies at the pathway level, pathway‐based meta‐analysis can be performed. Paired or partially paired samples are common in biomedical research. However, there are currently no existing pathway‐based meta‐analysis methods appropriate for paired or partially paired study designs. In this study, we developed a pathway‐based meta‐analysis approach for paired or partially paired samples. Meta‐analysis on the transcriptomics profiles were conducted using p‐value‐based, rank‐based, and effect size‐based algorithms. The application of our approach was demonstrated using partially paired data from psoriasis transcriptomics studies. Upon combining six transcriptomics studies, genes related to the cell cycle and DNA replication pathways are found to be highly perturbed in psoriatic lesional skin samples. Results were validated externally with independent RNA‐Seq data. Comparison with existing pathway meta‐analysis methods revealed consistent results, with our method showing higher detection power. This study demonstrated the utility of our newly developed pathway‐based meta‐analysis that allows the incorporation of partially paired or paired samples. The proposed framework can be applied to omics data including but not limited to transcriptomics data.