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Why do pathway methods work better than they should?
Author(s) -
Szalai Bence,
SaezRodriguez Julio
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14011
Subject(s) - biological pathway , pathway analysis , gene , signal transduction , gene expression , biology , transcription factor , computational biology , metabolic pathway , regulation of gene expression , genetics
Pathway analysis methods are frequently applied to cancer gene expression data to identify dysregulated pathways. These methods often infer pathway activity based on the expression of genes belonging to a given pathway, even though the proteins ultimately determine the activity of a given pathway. Furthermore, the association between gene expression levels and protein activities is not well‐characterized. Here, we posit that pathway‐based methods are effective not because of the correlation between expression and activity of members of a given pathway, but because pathway gene sets overlap with the genes regulated by transcription factors (TFs). Thus, pathway‐based methods do not inform about the activity of the pathway of interest but rather reflect changes in TF activities.