Table 1 Summary of features used in the prioritization of MS-PRGs and validation
Feature | Description |
|---|---|
Bayesian framework (refined version of iRIGS) features | |
Genetic variants in MS | 200 genetic variants from the currently largest MS GWAS with genome-wide significance |
Functional Annotation of the Mammalian Genome 5 (FANTOM5) | Annotations of mammalian regulatory components, such as promoters, enhancers lncRNAs and miRNAs (provided by original iRIGS analysis) |
Genome-scale chromosome conformation capture (Hi-C) | Brain Hi-C data including both short- and long-range interactions among genomic loci (provided by original iRIGS analysis) |
Expression in MS brain tissue | Differentially expressed genes in MS brain tissue from 21 post-mortem brain samples (11 MS cases and 10 control subjects) |
DNA methylation in MS brain tissue | Differentially methylated genes from epigenome-wide changes in DNA methylation levels of 28 MS cases and 19 control subjects |
Gene–gene relationships | Gene interactions from Gene Ontology (GO) network (provided by original iRIGS analysis) |
Two-sample Mendelian randomization (2SMR) feature | |
Expression quantitative trait loci (eQTL) | Top cis-eQTL of 19 tissues based on tissue expression data from the Genotype-Tissue Expression (GTEx) portal |
Genetic features used in validation | |
Probability of loss of function (LoF) intolerant (pLI) scores | A high pLI score indicates the gene is more likely to be intolerant towards protein-truncating variant(s) |
Evolutionary rate | The ratio of nonsynonymous over synonymous substitution rate (dN/dS) |
Genes of human diseases | From OMIM and ClinVar databases |
Cell type features used in validation | |
Single-nuclei RNA-sequencing (snRNA-seq) | Cell type-specificity enrichment analysis using a snRNA-seq dataset from the brain tissue of 4 progressive MS patients and 5 non-neurological controls |
Drug features used in validation | |
MS drug targets | 32 MS drug targets were collected from the DrugBank database, followed by the enrichment analysis |
Connectivity Map (CMap) drug signatures | The co-expressed gene-set enrichment analysis (Cogena) R package was performed for the downregulated and upregulated 100 CMap gene sets |