Fig. 4: Differentially transcribed RiPP families in multi-disease case-control cohorts.

a The bar plot displays the number of RiPP precursor families that are significantly enriched in the healthy group (top) or the disease group (bottom). Statistical significance was determined using criteria of |log2 fold change | ≥1 and adjusted p values ≤ 0.05. b The intersection of differentially transcribed RiPP precursor families that are enriched in healthy groups compared to multiple disease groups. The top bar plot and connecting lines represent the differential RiPP precursor families identified in the corresponding disease case-control cohorts. Precursor families are highlighted in different colors based on their RiPP classes.*Families chosen to tested bioactivity in this study. c The workflow for predicting the mature AIP uses the reported AIP-I from Staphylococcus aureus as an illustrative example (Method). d Chemically synthesized AIPs with antibiofilm or anti-inflammatory activity in this study. Here, the compound name consists of the family name and a specific suffix denoting its characteristics. For example, “et_L1” indicates that the AIP has an exotail with a length of 1 amino acid, “et_free” signifies an AIP without an exotail, “c” denotes cyclopeptides, and “t” represents exotail-free AIPs with a thiolactone group. e, f n = 3 biological samples for each experiment, 2 independent experiments. Significance was determined using one-way ANOVA test. e Anti-biofilm activity of AIPs against pathogenic biofilm by pathogens. n = 3 biologically independent samples. f Anti-inflammatory activity of BF_94_et_L1 in RAW264.7 cell lines. Bars represent mean ± standard error. For all p values, p < 0.05 mean significant difference compared with the control group. Exact adjusted p-values from left to right are: <1e−15, 1.248e−5, 1.866e−5, and 2.706e−12 in TNFα (upper) and <1e−15, 0.0089, 0.0006, and 6.055e−7 in IL-6 (lower).