Fig. 2: RiPP precursor peptides present a hypervariable chemical diversity and novelty.

a RiPP precursors retained for downstream analysis. Upper: Two circles in different colors represent the RiPP precursor peptides identified by DeepRiPP and TrRiPP. The red-circled area highlights the precursors that were retained for downstream analysis. Bottom: The stacked barplot illustrates the proportion of RiPP precursors retained for analysis. b The outer barplot displays the count of precursor sequences for nine RiPP classes, while the inner stacked barplot represents the distribution of precursor length. c Uniform Manifold Approximation and Projection (UMAP) plot showing the chemical space of RiPP precursors obtained from the human microbiome (black dots) and experimentally validated RiPP precursors deposited in the MIBiG 3.0 database (red dots). d Multi-Dimensional Scaling (MDS) plot displays the chemical diversity of predicted mature precursors within and between RiPP classes. Dot size signifies the count of unique precursor sequences per class, color indicates median Tanimoto coefficient reflecting class similarity, and distance between dots represents similarity among different RiPP classes. e, f Classify the novelty of RiPP families based on their precursor and genomic neighborhood (Supplementary Information). e The chord diagram illustrates the novelty of identified precursor families (left panel) for nine different RiPP classes (right panel). The novelty of RiPP precursor families into “MIBiG” (homologous to characterized precursors in MIBiG), families with RiPP-associated domains (1, Graspetide (3 families), 2, Lanthipeptide (31 families), 3, Lassopeptide (26 families), 4, Thiopeptide (5 families), 5, RiPP-like (25 families), 6, LAP (19 families), and 7, other known RiPPs (2 families)), and “Uncharacterized RiPP” families. Numbers in brackets indicate the count per category. f RiPP families are classified as Classic RiPP (known precursor homology and defined genomic neighborhood), Uncharacterized RiPP (no known precursor homology or novel genomic neighborhood), and Others (remaining families).