Supplementary Analyses and Figures Huntington ́s Disease and its therapeutic target genes: A global functional profile based on the HD Research Crossroads database

1. Enrichment analyses of the unfiltered set of genes curated in HD Crossroads For the analysis presented in the main text, a filtered set of genes from HD Crossroads was used. Filtering was performed using the Target Validation Score (TVS). Genes were only included with a corresponding TVS equal or larger than 3.0, i.e. for which a causal relationship has been deduced from experiments in a HD model, or which were indicated in an association or linkage study. In contrast, lower TVS can imply that a gene: has an altered pathway or functional activity in HD (TVS = 2.5); displays altered expression or cellular distribution in HD, or its corresponding protein binds to mutant Htt (TVS= 2.0); is active in HD-relevant brain regions or is linked to HD-associated biological mechanism (TVS=1.0); or is implicated in neurodegeneration based on genome-wide screens (TVS=0). As the inclusion of low-scoring genes may provide indication for additional disease-relevant mechanisms, enrichment analyses for GO categories, KEGG pathways and Pfam families were also carried out on the full list of genes from HD Crossroads. They include 805 genes downloaded from the HD Crossroads web-site (http://www.hdresearchcrossroads.org), as well as 162 genes that were provided directly by the curators of HD Crossroads. The same thresholds for significance and minimum number of genes were applied to these analyses as for those presented in our paper. Our results can be found in the Additional files 2-6.