High-resolution deconvolution of cell-type specific transcriptional regulatory signals from bulk sequencing samples – 

Abstract: Biological systems exhibit remarkable heterogeneity, orchestrated by the complex interplay among diverse cell types. Gaining insight into the regulatory processes within these cells is crucial for understanding both developmental mechanisms and disease etiologies. Although single-cell sequencing has greatly enhanced our knowledge of individual cellular functions, most sequencing assays optimized to capture regulatory signals are designed for bulk samples. Here, we introduce a novel computational framework, DEconvolution of Tissue profiles with Accurate Interpretation of Locus-specific Signals (DETAILS), that enables the reconstruction of cell-type-specific genomic signals at high resolution from bulk sequencing samples. Our results demonstrate the adaptability of DETAILS across various omics datasets, including nascent transcript sequencing and ChIP-seq for chromatin modifications.