Inferring Disease Progressive Stages in Single-Cell Transcriptomics Using Weakly-Supervised Deep Learning Approach
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Background
Application of single-cell/nucleus genomic sequencing to patient-derived tissues offers potential solutions to delineate disease mechanisms in human. However, individual cells in patient-derived tissues are in different pathological stages, and hence such cellular variability impedes subsequent differential gene expression analyses.
Result
To overcome such heterogeneity issue, we present a novel deep learning approach, scIDST, that infers disease progressive levels of individual cells with weak supervision framework. The inferred disease progressive cells displayed significant differential expression of disease-relevant genes, which could not be detected by comparative analysis between patients and healthy donors. In addition, we demonstrated that pre-trained models by scIDST are applicable to multiple independent data resources, and advantageous to infer cells related to certain disease risks and comorbidities.
Conclusion
Taken together, scIDST offers a new strategy of single-cell sequencing analysis to identify bona fide disease-associated molecular features.
