scSemiProfiler: Advancing large-scale single-cell studies through semi-profiling with deep generative models and active learning

Jingtao Wang, Gregory J. Fonseca and Jun Ding ()
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Jingtao Wang: Research Institute of McGill University Health Centre
Gregory J. Fonseca: Research Institute of McGill University Health Centre
Jun Ding: Research Institute of McGill University Health Centre

Nature Communications, 2024, vol. 15, issue 1, 1-27

Abstract: Abstract Single-cell sequencing is a crucial tool for dissecting the cellular intricacies of complex diseases. Its prohibitive cost, however, hampers its application in expansive biomedical studies. Traditional cellular deconvolution approaches can infer cell type proportions from more affordable bulk sequencing data, yet they fall short in providing the detailed resolution required for single-cell-level analyses. To overcome this challenge, we introduce “scSemiProfiler”, an innovative computational framework that marries deep generative models with active learning strategies. This method adeptly infers single-cell profiles across large cohorts by fusing bulk sequencing data with targeted single-cell sequencing from a few rigorously chosen representatives. Extensive validation across heterogeneous datasets verifies the precision of our semi-profiling approach, aligning closely with true single-cell profiling data and empowering refined cellular analyses. Originally developed for extensive disease cohorts, “scSemiProfiler” is adaptable for broad applications. It provides a scalable, cost-effective solution for single-cell profiling, facilitating in-depth cellular investigation in various biological domains.

Date: 2024
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DOI: 10.1038/s41467-024-50150-1

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