Fig. 6: A use case of the Interactive Mapping module using DNMT3A base-editing screens.

a, The user interface of the Interactive Mapping. From ‘start with a gene/protein identifier’, users are asked to select a gene (DNMT3A), structure (PDB 4U7T) and upload annotations (variants, to be shown as spheres; continuous data or scores, to be shown as a heat map; and discrete data or features, to be shown in discrete colors). The selected gene, structure and entered annotations can be edited by going back through the workflow. Finally, in ‘view results’, annotations are visible on sequence (left) and structure (right). The annotation tracks are selectable from the sequence viewer to map specific tracks on the structure. For example, the mapping on the structure viewer (right) is the result of clicking the ‘base-edited position’ and ‘domain’ tracks, where variation data are shown as red spheres and domain annotations are displayed as features in different colors. Colors are editable by the users. b, Illustration of the concurrent mapping of user-uploaded variant annotations and data from additional G2P-provided resources on the structure (‘Resources in the G2P portal’ in Results). Top, the Base-edited positions (red spheres) and the ClinVar PLP variants (orange spheres) are simultaneously mapped on the structure (MORC2, PDB 7PFP). Bottom, the base-edited positions (red spheres) are displayed in the context of secondary structure annotations (as discrete features) available in the portal. c, Illustration of the concurrent mapping of user-uploaded variants, features and scores on the structure. Top, base-edited positions (red spheres) in the context of pLDDT values (four discrete features: very high, confident, low and very low); bottom, user-provided base-edited positions (red spheres) in the context AlphaMissense³⁵ pathogenicity scores (green spectrum) where darker green indicates higher pathogenicity scores. After performing a workflow in the Interactive Mapping, users can download the current mappings as a TSV file (protein residue-wise annotation) and a PyMOL-compatible structure file.