Background:
BioCyc (https://www.biocyc.org) is a web portal hosting over 20,000 microbial pathway/genome databases (PGDBs), with integrated tools for analysing metabolic reactions and pathways, enzymes, genes, regulation, transport and protein complexes. BioCyc PGDBs are built from annotated genomes using computational inference and imported data sources, with high-priority genomes refined through manual curation. Manual curation corrects computational errors and incorporates experimental evidence, emphasising the notable biology of each organism.
Pathogenic Neisseria are a continuing priority for researchers and public health, driven by rising antimicrobial resistance and the difficulty of maintaining accurate genome annotations in the presence of various phase-variable gene families. In 2024, BioCyc (www.biocyc.org) released a manually curated PGDB for Neisseria gonorrhoeae FA 1090, providing a high-quality genome annotation for the gonococcal research community. Given the epidemiological significance of Neisseria meningitidis, we then implemented an ortholog propagation workflow to aid the manual curation of a PGDB for the reference genome of this species, serogroup B strain MC58.
Aim/Methods:
To generate and manually curate a high-quality BioCyc PGDB for N. meningitidis MC58, leveraging curation efforts on the N. gonorrhoeae FA 1090 PGDB with the aid of an ortholog propagation workflow with curator oversight.
Results:
The PGDB for N. meningitidis MC58 (released Dec 2025) benefited greatly from our ortholog propagation workflow, resulting in the transfer of manually curated data for 243 calculated orthologs. In addition to capturing core metabolism and transport, this PGDB prioritises accurate representation of notable meningococcal biology, particularly genes associated with pathogenesis. As with the manually curated PGDB for N. gonorrhoeae FA 1090, particular attention was given to the correct annotation of phase-variable loci, including the reconstruction of incorrectly annotated pseudogenes.
Critically, in addition to N. meningitidis MC58, curated data was also propagated to all other gonococcal and meningococcal PGDBs (n = 127), significantly improving the quality of all PGDBs for both species.
Conclusions:
Manually curated reference genomes for both N. gonorrhoeae and N. meningitidis should prove a useful resource for researchers working on pathogenic Neisseria. Our ortholog propagation workflow also positions BioCyc's gonococcal and meningococcal PGDBs as an ideal dataset for BioCyc’s powerful built-in comparative genomic analysis tools.