Guided-topic modelling of single-cell transcriptomes enables joint cell-type-specific and disease-subtype deconvolution of bulk transcriptomes with a focus on cancer studies
Swapna, L. S.; Huang, M.; Li, Y.
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Cell-type composition is an important indicator of health. We present Guided Topic Model for deconvolution (GTM-decon) to automatically infer cell-type-specific gene topic distributions from single-cell RNA-seq data for deconvolving bulk transcriptomes. GTM-decon performs competitively on deconvolving simulated and real bulk data compared with the state-of-the-art methods. Moreover, as demonstrated in deconvolving disease transcriptomes, GTM-decon can infer multiple cell-type-specific gene topic distributions per cell type, which captures sub-cell-type variations. GTM-decon can also use phenotype labels from single-cell or bulk data as a guide to infer phenotype-specific gene distributions. In a nested-guided design, GTM-decon identified cell-type-specific differentially expressed genes from bulk breast cancer transcriptomes.
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