High-resolution digital dissociation of brain tumors with deep multimodal autoencoder
Sun, J.; Pan, Y.; Lin, T.; Smith, K.; Onar-Thomas, A.; Robinson, G. W.; Zhang, W.; Northcott, P. A.; Li, Q.
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In single cell biology, the complexity of tissues may hinder lineage cell mapping or tumor microenvi-ronment decomposition, requiring digital dissociation of bulk tissues. Many deconvolution methods focus on transcriptomic assay, not easily applicable to other omics due to ambiguous cell markers and reference-to-target difference. Here, we present MODE, a multimodal autoencoder pipeline linking multi-dimensional features to jointly predict personalized multi-omic profiles and cellular compositions, using pseudo-bulk data constructed by internal non-transcriptomic reference and external scRNA-seq data. MODE was evaluated through rigorous simulation experiments and real multiomic data from multiple tissue types, outperforming nine deconvolution pipelines with superior generalizability and fidelity.
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