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