Why do pathway methods work better than they should?

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. F...

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Main Authors: Szalai, Bence (Author) , Sáez Rodríguez, Julio (Author)
Format: Article (Journal)
Language:English
Published: 14 December 2020
In: FEBS letters
Year: 2020, Volume: 594, Issue: 24, Pages: 4189-4200
ISSN:1873-3468
DOI:10.1002/1873-3468.14011
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/1873-3468.14011
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/1873-3468.14011
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Author Notes:Bence Szalai and Julio Saez-Rodriguez

MARC

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520 |a 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. 
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