Fig. 4

The TGex analysis screen (SVs). SV analysis is exemplified by a list of recurrently mutated regulatory elements discovered in a cohort of patients with neurodevelopmental disorders [63]. The highlighted element overlaps the GH17J002188 GeneHancer, an intronic enhancer of the gene SMG6. Remarkably, this enhancer also targets the WDR81 gene (over ~ 476 kb), with a higher VarElect score for the relevant phenotype (neurodevelopmental, “developmental delay”, etc') than SMG6. a The main analysis area for SVs is divided into 3 sections, including the main section listing the SV events (left), the detailed event section (top, right) presenting a detailed view of the list of genes and GeneHancer regulatory elements that are affected by the event, and the genomic view section (bottom, right) allowing visual examination of the genomic context of each event. b Expanded view of the event genomic context. c Clicking on the Phenotype score for a given GeneHancer opens the VarElect MiniCard for the element-gene-phenotype association. At the top part of the MiniCard, evidence describing the GeneHancer and its association with the gene target is detailed. This includes a list of sources for the identification of the element; a list of transcription factors found to have binding sites within the element; a detailed view of the evidence for element-gene associations. Below the GeneHancer details appear the classic gene-phenotype MiniCards as described in Fig. 3. Importantly, the score used for prioritization in the SV module is calculated by combining the GeneHancer confidence score of the element and of the element-gene association, with the classic VarElect gene-phenotype score of the element target gene