Multimodal joint deconvolution and integrative signature selection in proteomics

Deconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL. Presenting a deconvolution algorithm to dissect the bulk proteome by leveraging the information shared between the transcriptome and proteome, the output can be used for further downstream analyses, such as cs-protein Quantitative Trait Loci (cspQTL) mapping and cell type-specific pathology.