CATH (https://www.cathdb.info) identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural and functional annotations. There are two levels: CATH-B, a daily snapshot of the latest domain structures and superfamily assignments, and CATH+, with additional derived data, such as predicted sequence domains, and functionally coherent sequence subsets (Functional Families or FunFams). The latest CATH+ release, version 4.3, significantly increases coverage of structural and sequence data, with an addition of 65,351 fully-classified domains structures (+15%), providing 500 238 structural domains, and 151 million predicted sequence domains (+59%) assigned to 5481 superfamilies. The FunFam generation pipeline has been re-engineered to cope with the increased influx of data. Three times more sequences are captured in FunFams, with a concomitant increase in functional purity, information content and structural coverage. FunFam expansion increases the structural annotations provided for experimental GO terms (+59%). We also present CATH-FunVar web-pages displaying variations in protein sequences and their proximity to known or predicted functional sites. We present two case studies (1) putative cancer drivers and (2) SARS-CoV-2 proteins. Finally, we have improved links to and from CATH including SCOP, InterPro, Aquaria and 2DProt.

Women with Systemic Lupus Erythematosus (SLE) show significantly increased cardiovascular risk compared to the general population. However, despite CVD being a major cause of morbidity and mortality for these women, this increased risk is not managed clinically and tools to dissect and predict their cardiovascular risk are lacking. Notably, this elevated CVD risk is not captured by traditional risk factors. To explore molecular programs underlying asymptomatic atherosclerosis in SLE we used a well-characterised cohort of CVD-free women with SLE, scanned for asymptomatic atherosclerotic plaques using non-invasive ultrasound imaging of the carotid and femoral arteries. We investigated the transcriptomic profiles of CD14+ circulating monocytes in women with SLE with or without preclinical atherosclerosis. We identified unique monocytic gene expression profiles that distinguished the presence of preclinical plaques in women with SLE. In addition, advanced bioinformatic analysis revealed functional pathways and interactions between the genes identified that could explain mechanistic differences in plaque formation. We propose that these molecular signatures could help understand why a subset of women with SLE are predisposed to develop atherosclerosis and at higher risk of developing clinical CVD. Collectively with other efforts, these molecular insights will help to better define atherosclerosis in the context of SLE which will be critical for future patient stratification and identification of anti-atherosclerotic therapies.