Tissue-adjusted pathway analysis of cancer (TPAC): A novel approach for quantifying tumor-specific gene set dysregulation relative to normal tissue.

Autor: H Robert Frost
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS Computational Biology, Vol 20, Iss 1, p e1011717 (2024)
Druh dokumentu: article
ISSN: 1553-734X
1553-7358
DOI: 10.1371/journal.pcbi.1011717&type=printable
Popis: We describe a novel single sample gene set testing method for cancer transcriptomics data named tissue-adjusted pathway analysis of cancer (TPAC). The TPAC method leverages information about the normal tissue-specificity of human genes to compute a robust multivariate distance score that quantifies gene set dysregulation in each profiled tumor. Because the null distribution of the TPAC scores has an accurate gamma approximation, both population and sample-level inference is supported. As we demonstrate through an analysis of gene expression data for 21 solid human cancers from The Cancer Genome Atlas (TCGA) and associated normal tissue expression data from the Human Protein Atlas (HPA), TPAC gene set scores are more strongly associated with patient prognosis than the scores generated by existing single sample gene set testing methods.
Databáze: Directory of Open Access Journals
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