Pep2Path

Pep2Path automates the matching of tandem mass spectrometry-derived mass shift sequences to biosynthetic gene clusters to link nonribosomally and ribosomally synthesized bioactive peptides to their genomic origins for peptidogenomics-driven natural product discovery.

Key Features:

• Automated Matching: Automates matching of mass shift sequences from tandem mass spectra to corresponding biosynthetic gene clusters (BGCs).
• Bayesian Probabilistic Approach: Employs a rapid Bayesian probabilistic method to score and match identified mass spectra with candidate BGCs.
• Mass-spectrometry-based Peptidogenomics: Integrates peptidogenomics by linking MS-derived peptide evidence to genomic BGCs for peptidic metabolite identification.
• High-Throughput Capability: Handles large datasets, including hundreds of genomes, enabling large-scale correlation of spectra and BGCs.
• Cross-Species Identification: Identifies candidate biosynthetic gene clusters across different bacterial subphyla, for example detecting a cluster in a Proteobacteria genome distinct from the source organism.

Scientific Applications:

• Biosynthetic Gene Cluster Identification: Connects nonribosomal and ribosomally synthesized peptides to their BGCs to reveal biosynthetic origins of bioactive peptides.
• Natural Product Discovery: Facilitates discovery of novel peptidic metabolites and potential therapeutic compounds such as antibiotics, immunosuppressants, and cytostatics.
• Comparative Genomics and Microbial Diversity Exploration: Enables matching of compounds from unsequenced organisms to closely related BGCs in sequenced genomes to explore biosynthetic diversity.

Methodology:

Integrates tandem mass spectrometry data (mass shift sequences from tandem mass spectra) with genomic information using a rapid Bayesian probabilistic framework to automate matching of spectra to biosynthetic gene clusters across large genome datasets.