MS data linked to manuscript: https://doi.org/10.1101/2025.08.11.669102

26 SUPPLEMENTARY MATERIAL 702 FIGURES 703 704 705 Supplementary Figure 1: Histograms showing the number of BGCs per GCF across the dataset. a GCF size distribution plotted on a logarithmic x-axis to highlight the longtail structure of large families. b The same distribution shown on a linear scale, excluding singletons. The majority of GCFs consist of only a few BGCs, while a small subset include GCFs with hundreds of BGCs. a b 27 706 Supplementary Figure 2: Correlation between GCF size and PanBGC openness (γ-value). Scatterplot showing the relationship between the number of BGCs per gene cluster family (GCF size) and the corresponding gamma (γ) value calculated by the PanBGC framework, which quantifies openness based on Heaps’ law. Each point represents a GCF. A sligh t positive trend is observed (Spearman’s ρ = 0.029), indicating minimal correlation between family size and openness. The black line represents a linear regression fit with a 95% confidence interval (shaded area). 28 707 Supplementary Figure 3: Cblaster database construction pipeline and user query. Multiple GCFs results from ZOL are processed using a Python script (Max_BGC.py) to create a theoretical maximum BGC for each family. These maximum BGCs are then used to build a searchable DIAMOND database using the cblaster makedb module. A userprovided query BGC is subsequently searched against this database using cblaster search. The result identifies the best-matching family based on sequence similarity and hit coverage, which is displayed in a ranked table of candidate families. 29 TABLES 708 Supplementary Table 1: Overview of json, excel and nexus files used for data storage. 709 File Description Overview.json Contains summary information about all GCFs. Used for overview table creation. mibig_compound.json Contains information about mibig compounds and their family. Used for Compound overview table. BGC_analysis_results.xlsx Contains statistics of pfam domains found in each class. Gamma_value_bgc_data.json Contains summary information about the gamma calculation of each GCF. gbk_inf.json Available for each GCF. Contains information about each cluster in the GCF, and stores domain structure of each BGC genbank_data.json Available for each GCF. Contains different annotations for each gene and cluster part of the GCF Heaps_law.json Available for some GCF. Contains simulation order for heap’s law calculation Nexus.nex Available for some GCF. Stores OG trees and the coalescent tree in nexus format. Used for tanglegram creation. Report.json Available for each GCF. Contains summary of ZOL run for the GCF. The files can be found under: https://github.com/ZiemertLab/PanBGC-710 DB/tree/master/Website_code/public/data 711