parent-product-relationship-tracking
Summary
Maintain and serialize parent–product relationships when applying biotransformation rules to input molecular structures, enabling traceability of how candidate molecules are derived from anchor compounds. This is essential for validating structure predictions and reconstructing the chemical transformation pathway in untargeted metabolomics annotation.
When to use
When you have applied biotransformation rules to generate candidate product structures from a set of input molecules (represented as SMILES strings) and need to document which product structures were derived from which parent structures. Critical in metabolomics workflows where you must rank or evaluate candidates by their transformation distance from the anchor compound, or when you need to report the applied rule for each transformation.
When NOT to use
- Input molecules are already annotated with known identities and you only need to confirm their structures, not discover new candidates.
- Biotransformation rules are not available or not applicable to your molecule class (e.g., inorganic compounds, non-metabolic transformations).
- You are filtering an existing suspect library rather than generating de novo candidates from input anchors.
Inputs
- SMILES strings for input molecules (parsed and validated by RDKit)
- Biotransformation rules encoded in BAM codebase or loaded from reaction datasets (e.g., KEGG, RetroRules)
- Parent–product pairs from rule application engine
Outputs
- Structured output file (JSON or CSV) with columns: original SMILES, applied rule identifier, product SMILES, transformation metadata
- Deduplicated set of candidate product structures with parent–product relationship graph
How to apply
After applying each biotransformation rule to every input structure using RDKit and the BAM rule engine, collect the transformed structures and maintain an explicit mapping of parent SMILES → applied rule identifier → product SMILES. Deduplicate product structures while preserving all parent–product edges; if multiple rules or parents generate the same product, record each path. Serialize the complete parent–product graph (with rule metadata) to a structured output file (JSON or CSV), ensuring each record contains original SMILES, applied rule identifier, product SMILES, and transformation metadata. This traceability allows downstream ranking algorithms (e.g., GNN-SOM site-of-metabolism prediction) to score candidates by transformation specificity and chemical plausibility.
Related tools
- RDKit (Parse, validate, and manipulate SMILES strings; execute biotransformation rule application on molecular structures)
- HassounLab/BAM (Implement biotransformation rule engine and orchestrate parent–product relationship tracking within the annotation method) — https://github.com/HassounLab/BAM
- HassounLab/GNN-SOM (Predict site-of-metabolism and rank candidate products by their parent–product relationships and transformation plausibility) — https://github.com/HassounLab/GNN-SOM
- KEGG or RetroRules (Provide the biotransformation rules (reaction definitions) applied to generate products from parent structures)
Examples
sh runBAM.sh
Evaluation signals
- Every product SMILES can be traced back to at least one parent SMILES and one applied rule identifier; no orphaned products.
- Deduplicated product set contains no duplicate SMILES entries, but the parent–product mapping records multiple derivation paths when applicable.
- Output file schema conforms to specified columns (original SMILES, rule ID, product SMILES, metadata); all rows are valid and parseable.
- Product SMILES are chemically valid and consistent with the biotransformation rule definitions (spot-check by comparing rule mechanism to product structure).
- Parent–product graph has no cycles (transformations are acyclic, flowing from input anchors outward to products).
Limitations
- Biotransformation rule coverage is limited to the reaction dataset specified (KEGG, RetroRules, or custom); rules absent from the dataset will not generate corresponding products, potentially missing true metabolites.
- SMILES parsing and validation depend on RDKit's chemical inference; invalid or ambiguous SMILES may be silently dropped or misinterpreted, introducing false negatives.
- Parent–product relationships do not themselves rank or prioritize candidates; ranking requires downstream integration with site-of-metabolism prediction (e.g., GNN-SOM) or spectral matching.
- Deduplication of product SMILES is exact-match only; tautomers, stereoisomers, or alternative SMILES representations of the same molecule are treated as distinct, potentially inflating the candidate pool.
Evidence
- [other] Collect and deduplicate the transformed structures, maintaining parent–product relationships.: "Collect and deduplicate the transformed structures, maintaining parent–product relationships."
- [other] Serialize the results as a structured output file (JSON or CSV) containing original SMILES, applied rule identifier, product SMILES, and transformation metadata.: "Serialize the results as a structured output file (JSON or CSV) containing original SMILES, applied rule identifier, product SMILES, and transformation metadata."
- [other] BAM is implemented as a method that uses biotransformation rules and global molecular networking for molecular structure discovery from untargeted metabolomics data.: "BAM is implemented as a method that uses biotransformation rules and global molecular networking for molecular structure discovery from untargeted metabolomics data."
- [readme] To change to using RetroRules reaction data, simply comment the "KEGG biotransformations" block and uncomment the "RetroRules biotransformations" box, and then run the runBAM.sh file.: "To change to using RetroRules reaction data, simply comment the "KEGG biotransformations" block and uncomment the "RetroRules biotransformations" box, and then run the runBAM.sh file."
1---2name: parent-product-relationship-tracking3description: Use when when you have applied biotransformation rules to generate candidate product structures from a set of input molecules (represented as SMILES strings) and need to document which product structures were derived from which parent structures.4license: CC-BY-4.05---67# parent-product-relationship-tracking89## Summary1011Maintain and serialize parent–product relationships when applying biotransformation rules to input molecular structures, enabling traceability of how candidate molecules are derived from anchor compounds. This is essential for validating structure predictions and reconstructing the chemical transformation pathway in untargeted metabolomics annotation.1213## When to use1415When you have applied biotransformation rules to generate candidate product structures from a set of input molecules (represented as SMILES strings) and need to document which product structures were derived from which parent structures. Critical in metabolomics workflows where you must rank or evaluate candidates by their transformation distance from the anchor compound, or when you need to report the applied rule for each transformation.1617## When NOT to use1819- Input molecules are already annotated with known identities and you only need to confirm their structures, not discover new candidates.20- Biotransformation rules are not available or not applicable to your molecule class (e.g., inorganic compounds, non-metabolic transformations).21- You are filtering an existing suspect library rather than generating de novo candidates from input anchors.2223## Inputs2425- SMILES strings for input molecules (parsed and validated by RDKit)26- Biotransformation rules encoded in BAM codebase or loaded from reaction datasets (e.g., KEGG, RetroRules)27- Parent–product pairs from rule application engine2829## Outputs3031- Structured output file (JSON or CSV) with columns: original SMILES, applied rule identifier, product SMILES, transformation metadata32- Deduplicated set of candidate product structures with parent–product relationship graph3334## How to apply3536After applying each biotransformation rule to every input structure using RDKit and the BAM rule engine, collect the transformed structures and maintain an explicit mapping of parent SMILES → applied rule identifier → product SMILES. Deduplicate product structures while preserving all parent–product edges; if multiple rules or parents generate the same product, record each path. Serialize the complete parent–product graph (with rule metadata) to a structured output file (JSON or CSV), ensuring each record contains original SMILES, applied rule identifier, product SMILES, and transformation metadata. This traceability allows downstream ranking algorithms (e.g., GNN-SOM site-of-metabolism prediction) to score candidates by transformation specificity and chemical plausibility.3738## Related tools3940- **RDKit** (Parse, validate, and manipulate SMILES strings; execute biotransformation rule application on molecular structures)41- **HassounLab/BAM** (Implement biotransformation rule engine and orchestrate parent–product relationship tracking within the annotation method) — https://github.com/HassounLab/BAM42- **HassounLab/GNN-SOM** (Predict site-of-metabolism and rank candidate products by their parent–product relationships and transformation plausibility) — https://github.com/HassounLab/GNN-SOM43- **KEGG or RetroRules** (Provide the biotransformation rules (reaction definitions) applied to generate products from parent structures)4445## Examples4647```48sh runBAM.sh49```5051## Evaluation signals5253- Every product SMILES can be traced back to at least one parent SMILES and one applied rule identifier; no orphaned products.54- Deduplicated product set contains no duplicate SMILES entries, but the parent–product mapping records multiple derivation paths when applicable.55- Output file schema conforms to specified columns (original SMILES, rule ID, product SMILES, metadata); all rows are valid and parseable.56- Product SMILES are chemically valid and consistent with the biotransformation rule definitions (spot-check by comparing rule mechanism to product structure).57- Parent–product graph has no cycles (transformations are acyclic, flowing from input anchors outward to products).5859## Limitations6061- Biotransformation rule coverage is limited to the reaction dataset specified (KEGG, RetroRules, or custom); rules absent from the dataset will not generate corresponding products, potentially missing true metabolites.62- SMILES parsing and validation depend on RDKit's chemical inference; invalid or ambiguous SMILES may be silently dropped or misinterpreted, introducing false negatives.63- Parent–product relationships do not themselves rank or prioritize candidates; ranking requires downstream integration with site-of-metabolism prediction (e.g., GNN-SOM) or spectral matching.64- Deduplication of product SMILES is exact-match only; tautomers, stereoisomers, or alternative SMILES representations of the same molecule are treated as distinct, potentially inflating the candidate pool.6566## Evidence6768- [other] Collect and deduplicate the transformed structures, maintaining parent–product relationships.: "Collect and deduplicate the transformed structures, maintaining parent–product relationships."69- [other] Serialize the results as a structured output file (JSON or CSV) containing original SMILES, applied rule identifier, product SMILES, and transformation metadata.: "Serialize the results as a structured output file (JSON or CSV) containing original SMILES, applied rule identifier, product SMILES, and transformation metadata."70- [other] BAM is implemented as a method that uses biotransformation rules and global molecular networking for molecular structure discovery from untargeted metabolomics data.: "BAM is implemented as a method that uses biotransformation rules and global molecular networking for molecular structure discovery from untargeted metabolomics data."71- [readme] To change to using RetroRules reaction data, simply comment the "KEGG biotransformations" block and uncomment the "RetroRules biotransformations" box, and then run the runBAM.sh file.: "To change to using RetroRules reaction data, simply comment the "KEGG biotransformations" block and uncomment the "RetroRules biotransformations" box, and then run the runBAM.sh file."
HolobiomicsLab 