Here, we propose DeCAF (DEconvoluted cell type Allele specific Function), a new method to identify cell-fraction (cf) QTLs in tumors by leveraging both allelic and total expression information. Applying DeCAF to RNA-seq data from TCGA, we identify 3664 genes with cfQTLs (at 10% FDR) in 14 cell types, a 5.63× increase in discovery over conventional interaction-eQTL mapping. cfQTLs replicated in external cell-type-specific eQTL data are more enriched for cancer risk than conventional eQTLs. Our new method, DeCAF, empowers the discovery of biologically meaningful cfQTLs from bulk RNA-seq data in moderately sized studies.
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