ISLET

ISLET estimates individual-specific and cell-type-specific transcriptome reference panels from repeatedly measured bulk gene expression data to improve signal deconvolution and enable cell-type-specific differential expression analysis.

Key Features:

• Individual-Specific Reference Panels: Constructs personalized reference panels for subjects with multiple observed samples to improve deconvolution of bulk gene expression data.
• Cell-Type-Specific Inference: Estimates cell-type-specific reference profiles enabling identification of expression patterns unique to specific cell types.
• Integration with Mixture Proportions: Integrates personalized reference panels with sample-by-cell-type mixture proportions to enhance accuracy of estimated cell type mixture proportions.
• Cell-Type-Specific Differential Expression (csDE) Testing: Performs tests to identify cell-type-specific differentially expressed genes.
• Modeling Repeated Measurements: Models repeatedly measured bulk gene expression to optimize sharing of information within each subject.
• Required Inputs: Accepts an observed mixture data matrix (features by samples), a sample-by-cell-type mixture proportions matrix, and sample-to-subject mapping information.

Scientific Applications:

• Longitudinal blood transcriptome studies: Applied to longitudinal transcriptome profiles from blood samples in a large observational study of young children to confirm cell-type-specific gene signatures associated with pancreatic islet autoantibodies.
• Method validation: Simulation studies validated performance for reference estimation and downstream cell-type-specific differential expression testing.

Methodology:

Models repeatedly measured bulk gene expression using inputs of an observed mixture data matrix (features by samples), a sample-by-cell-type mixture proportions matrix, and sample-to-subject mapping, and optimizes sharing of information within subjects to derive individual- and cell-type-specific reference panels and to conduct cell-type-specific differential expression tests.