OmicsTweezer: A distribution-independent cell deconvolution model for multi-omics Data.

Cell deconvolution estimates cell type proportions from bulk omics data, enabling insights into tissue microenvironments and disease. However, practical applications are often hindered by batch effects between bulk data and referenced single-cell data, a challenge that is frequently overlooked. To address this discrepancy, we developed OmicsTweezer, a distribution-independent cell deconvolution model. By integrating optimal transport with deep learning, OmicsTweezer aligns simulated and real data in a shared latent space, effectively mitigating data shifts and inter-omics distribution differences. OmicsTweezer is versatile, capable of deconvolving bulk RNA-seq, bulk proteomics, and spatial transcriptomics. Extensive evaluations on simulated and real-world datasets demonstrate its robustness and accuracy. Furthermore, applications in prostate and colon cancer showcase OmicsTweezer's ability to identify biologically meaningful cell types. As a unified deconvolution framework for multi-omics data, OmicsTweezer offers an efficient and powerful tool for studying disease microenvironments.