Table 1 Transcriptional features commonly or potentially used to identify malignant cells from scRNA-seq data
From: Identification of malignant cells in single-cell transcriptomics data
Commonly used features | |||
|---|---|---|---|
Feature/aberration | Readout | Comments | |
Expression of cell-of-origin-marker genes | Gene signature score | Not sufficient to distinguish between normal and malignant cells of the same type; usually combined with other features | |
Inter-patient tumor heterogeneity | Index of cluster mixing (e.g. LISI score, entropy) | Requires multiple samples; may be confounded by batch effects | |
Copy-number alterations | Copy-number profile/aneuploidy score | Requires a reference of “normal” ploidy; will not detect malignant cells without chromosomal alterations | |
Supporting features | |||
Feature/aberration | Readout | Comments | |
Single-nucleotide alterations and mutational burden | Mutations in known sites/total number of mutations | Works best when combined with WES of matched samples; limited by low-coverage of scRNA-seq technologies | |
Formation of fusion transcripts | Expression of fused genes | Specific to individual cancer types; limited by low-coverage of scRNA-seq technologies | |
Sustained proliferation | Signature score for cycling gene sets | Commonly measured as cycling enrichment by cluster | |
Pathway dysregulation | Signature score for altered pathway | Specific to individual cancer types | |
Potentially discriminating features | |||
Feature/aberration | Readout | Comments | |
MHC downregulation | Signature score for antigen-presenting machinery | Specific to individual cancer types, TMEs, or individual cancer sub-clones | |
Overexpression of checkpoint molecules | Checkpoint ligand expression | Limited evidence in scRNA-seq | |
Expression of telomerase subunits | Gene or signature score | Limited evidence in scRNA-seq | |
Metabolic signatures | Signature score | Adjacent normal cells may exhibit similar alterations | |
Pro-angiogenic signaling | Gene or signature score | Limited evidence in scRNA-seq | |
Drivers of invasion (EMT) | Signature score | Intermediate EMT states may be difficult to capture | |
Oncofetal reprogramming | Gene or signature score | Specific to individual cancer types | |
Number of unique expressed genes | Gene count | Can be confounded by heterogeneous sequencing depth | |
