Fig. 3

GenePy score profiles for seven independent patients diagnosed with IBD across selected genes from the NOD2 and TLR pathways. GenePy scores shown were implemented using the M-CAP deleteriousness (D) metric. To facilitate plotting, raw GenePy scores were transformed to Z-scores for each gene. Different colours depict individual patient profiles. Despite being diagnosed with the same disease, all individuals exhibit distinctive profiles across key genes implicated in key immune pathways. Some individuals have evidence of gene pathogenicity within the same pathway (e.g. IBD5 and IBD6) this is conferred through accumulated mutation in different genes – IBD6 has elevated gene-level scores for TAB1, CARD6 and MAPK3 while IBD5 may have impaired function in this pathway due to combined mutation in MAPK13, BP1 and NFKB1. Similarly, IBD1, IBD3 and IBD4 exhibit pathogenic profiles in TLR pathway genes only. These individual level data can be combined with disease phenotype, severity and treatment outcome data in machine learning models to better stratify patient cohorts and realise the promise of personalised medicine