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DynaMiCs - Dynamic cell-type deconvolution ensembles for Mapping in mixed Conditions

Seifert, N.; Engel, L.; Tauschke, J.; Sterr, T.; Demmer, J.; Mensching-Buhr, M.; Voelkl, D.; Grellscheid, S. N.; Beissbarth, T.; Goertler, F.; Zacharias, H.; Altenbuchinger, M.

2025-05-14 bioinformatics
10.1101/2025.05.08.652868 bioRxiv
Show abstract

Single-cell techniques facilitate the molecular analysis of individual cells, providing insights into cellular diversity, function, and the complexity of biological systems. However, their application is typically limited to small-scale studies involving individual or a few dozen samples, as a consequence of costs and experimental requirement. This complicates the inference of robust conclusions about populations. Bulk transcriptomics offers cost-efficient measurements with low experimental requirements. However, the cellular resolution is lost and only a complex linear combination of signals from multiple cells is observed. Thus, gene expression changes cannot be attributed to individual cells or cell populations. Cell-type deconvolution methods infer cellular compositions from bulk transcriptomics data. State-of-the-art approaches use single-cell data to build molecular reference profiles and identify powerful cell-type markers for improved deconvolution. In this context, we propose Dynamic cell-type deconvolution ensembles for Mapping in mixed Conditions (DynaMiCs) for the integration of single-cell and bulk transcriptomics data. Specifically, DynaMiCs dynamically extracts information from single-cell experiments to (1) provide more accurate estimates of cellular compositions, and (2) establish a mapping between bulk and single-cell data. Consequently, DynaMiCs enables the investigation of how cell populations change in both quantity and molecular characteristics between different phenotypes, informed by single-cell experiments.

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