identifier: traitmech:000464 label: DS-42 system definition: A phage defense system in which an organism possesses the three-gene DefensePredictor-discovered system 42 locus cataloged as working transcriptional unit PRO1 and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing. definition_source: DOI:10.1126/science.adv7924 trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000209 synonyms: - synonym_text: DS-42 synonym_type: EXACT_SYNONYM source: DOI:10.1126/science.adv7924 - synonym_text: PRO1 synonym_type: RELATED_SYNONYM source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx - synonym_text: DS-42__DS-42A synonym_type: RELATED_SYNONYM source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md - synonym_text: DS-42__DS-42B synonym_type: RELATED_SYNONYM source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md - synonym_text: DS-42__DS-42C synonym_type: RELATED_SYNONYM source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md evidence: - reference: DOI:10.1126/science.adv7924 snippet: To test for anti-phage defense, we placed each TU with its predicted native promoter region on a low-copy number plasmid in E. coli MG1655 and challenged these strains with a panel of 24 diverse E. coli phages (Fig. 3; fig. S2). In total, 42 (45% of 94) of the cloned TUs produced smaller plaque sizes or reduced the efficiency of plating (EOP) at least ten-fold relative to an empty vector control strain notes: DeWeirdt et al. experimentally validated 42 predicted transcriptional units as phage-defense systems in E. coli. - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: DeWeirdt et al. name validated transcriptional units as DefensePredictor discovered systems. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "PRO1\tNZ_QOXO01000016.1\tGCF_003334005.1\t-\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t661\t3061\tMBL fold metallo-hydrolase, hypothetical protein,\ \ hypothetical protein\tWP_001198055.1, WP_001024069.1, WP_249925928.1\t4.870544869418898\t\ 6.906754778648663\tTrue\tTrue\tPredicted novel defense gene\tDS-42" notes: The final Science supplementary Table S6 maps working_id PRO1 to DS_name DS-42, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 661-3061 with product accessions WP_001198055.1, WP_001024069.1, and WP_249925928.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tPRO1\t24-04-13\t\ 24-04-13_PRO1_CBT2_AAA4_TMRA.png\t5\t4\tY\t400000\t1.0969100130080565\t\tTrue\t\ \tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports a PRO1 assay row with a Bas1 phage readout and a -log(EOP) value of 1.097. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\tDS-42\tTrue" notes: The final Science supplementary Table S8 maps PRO1 to replicated display name DS-42. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\t3.0\t363.0\tWP_001198055.1\tMBL hydrolase\tcd07731\tComA-like_MBL-fold;\ \ Competence protein ComA, ComEC and related proteins\thhpred_9048500.hhr\t12.0\t\ 251.0\t0.998\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a high-probability MBL hydrolase HHpred hit for WP_001198055.1 in PRO1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\t2.0\t190.0\tWP_001024069.1\tDimerization\tPF16892.9\tCHS5_N ; Chitin\ \ biosynthesis protein CHS5 N-terminus\thhpred_3514574.hhr\t108.0\t166.0\t0.7787\t\ 2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a moderate-probability CHS5_N/Dimerization HHpred hit for WP_001024069.1 in PRO1. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| DS-42 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | ' notes: The pinned DefenseFinder article registry maps the DS-42 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42A | | DS-42 | Custom | 70 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42A as a custom DS-42 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42B | | DS-42 | Custom | 20 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42B as a custom DS-42 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42C | | DS-42 | Custom | 200 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42C as a custom DS-42 profile. causal_graphs: - graph_id: ds_42_locus_reduces_phage_plaquing title: DS-42 locus reduces bacteriophage plaquing description: Conservative system-level sketch linking the three-gene DS-42 locus to reduced bacteriophage plaquing without resolving DS-42 component function or molecular output. scope_status: NONMECHANISTIC scope_notes: The graph captures DS-42 as the validated PRO1 transcriptional unit with three product accessions, a high-probability MBL hydrolase HHpred row for WP_001198055.1, a moderate-probability CHS5_N/Dimerization HHpred row for WP_001024069.1, and three DefenseFinder DS-42 profile rows. It does not assert native host breadth, exact profile-to-protein correspondence, MBL hydrolase or CHS5_N interpretation, WP_249925928.1 function, DS-42 molecular activity, complete phage breadth, or DefenseFinder rule-level detection criteria. nodes: - node_id: ds_42_locus label: DS-42 locus node_type: GENETIC_ELEMENT description: A three-gene DefensePredictor-discovered system 42 locus represented in the pinned DefenseFinder HMM inventory by three DS-42 custom profiles. - node_id: reduced_phage_plaquing label: reduced bacteriophage plaquing node_type: BIOLOGICAL_PROCESS description: Reduced bacteriophage plaquing in cells carrying cloned PRO1. - node_id: ds_42_system_trait label: DS-42 system node_type: TRAIT grounding: traitmech:000464 description: Possession of a genome-encoded DS-42 phage-defense system. - node_id: phage_defense_system label: phage defense system node_type: TRAIT grounding: traitmech:000209 description: Possession of one or more genome-encoded immune systems that inhibit bacteriophage infection. edges: - subject: ds_42_locus predicate: contributes to predicate_id: RO:0002326 object: reduced_phage_plaquing description: The DS-42/PRO1 locus contributes to reduced bacteriophage plaquing in heterologous E. coli MG1655 plasmid-expression assays. evidence: - reference: DOI:10.1126/science.adv7924 snippet: To test for anti-phage defense, we placed each TU with its predicted native promoter region on a low-copy number plasmid in E. coli MG1655 and challenged these strains with a panel of 24 diverse E. coli phages (Fig. 3; fig. S2). In total, 42 (45% of 94) of the cloned TUs produced smaller plaque sizes or reduced the efficiency of plating (EOP) at least ten-fold relative to an empty vector control strain notes: DeWeirdt et al. describe the plasmid-based phage challenge used to validate predicted transcriptional units. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "PRO1\tNZ_QOXO01000016.1\tGCF_003334005.1\t-\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t661\t3061\tMBL fold metallo-hydrolase, hypothetical\ \ protein, hypothetical protein\tWP_001198055.1, WP_001024069.1, WP_249925928.1\t\ 4.870544869418898\t6.906754778648663\tTrue\tTrue\tPredicted novel defense\ \ gene\tDS-42" notes: The final Science supplementary Table S6 maps working_id PRO1 to DS_name DS-42, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 661-3061 with product accessions WP_001198055.1, WP_001024069.1, and WP_249925928.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tPRO1\t\ 24-04-13\t24-04-13_PRO1_CBT2_AAA4_TMRA.png\t5\t4\tY\t400000\t1.0969100130080565\t\ \tTrue\t\tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports a PRO1 assay row with a Bas1 phage readout and a -log(EOP) value of 1.097. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\tDS-42\tTrue" notes: The final Science supplementary Table S8 maps PRO1 to replicated display name DS-42. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\t3.0\t363.0\tWP_001198055.1\tMBL hydrolase\tcd07731\tComA-like_MBL-fold;\ \ Competence protein ComA, ComEC and related proteins\thhpred_9048500.hhr\t\ 12.0\t251.0\t0.998\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a high-probability MBL hydrolase HHpred hit for WP_001198055.1 in PRO1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\t2.0\t190.0\tWP_001024069.1\tDimerization\tPF16892.9\tCHS5_N\ \ ; Chitin biosynthesis protein CHS5 N-terminus\thhpred_3514574.hhr\t108.0\t\ 166.0\t0.7787\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a moderate-probability CHS5_N/Dimerization HHpred hit for WP_001024069.1 in PRO1. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42A | | DS-42 | Custom | 70 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42A as a custom DS-42 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42B | | DS-42 | Custom | 20 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42B as a custom DS-42 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42C | | DS-42 | Custom | 200 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42C as a custom DS-42 profile. - subject: reduced_phage_plaquing predicate: confers predicate_id: METPO:2007700 object: ds_42_system_trait description: DS-42-mediated phage plaquing reduction realizes the DS-42 system trait. evidence: - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "PRO1\tNZ_QOXO01000016.1\tGCF_003334005.1\t-\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t661\t3061\tMBL fold metallo-hydrolase, hypothetical\ \ protein, hypothetical protein\tWP_001198055.1, WP_001024069.1, WP_249925928.1\t\ 4.870544869418898\t6.906754778648663\tTrue\tTrue\tPredicted novel defense\ \ gene\tDS-42" notes: The final Science supplementary Table S6 maps working_id PRO1 to DS_name DS-42, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 661-3061 with product accessions WP_001198055.1, WP_001024069.1, and WP_249925928.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tPRO1\t\ 24-04-13\t24-04-13_PRO1_CBT2_AAA4_TMRA.png\t5\t4\tY\t400000\t1.0969100130080565\t\ \tTrue\t\tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports a PRO1 assay row with a Bas1 phage readout and a -log(EOP) value of 1.097. - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: The DS nomenclature is used for DefensePredictor discovered systems. - subject: ds_42_system_trait predicate: is a predicate_id: rdfs:subClassOf object: phage_defense_system description: DS-42 system possession is a phage-defense-system trait. evidence: - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: DeWeirdt et al. name validated TUs as DefensePredictor discovered systems. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| DS-42 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | ' notes: The pinned DefenseFinder article registry maps the DS-42 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science. discussions: - discussion_id: ds-42-defensefinder-model-gap prompt: Resolve DS-42 native host breadth, exact component activity, profile-to-protein mapping, MBL hydrolase and CHS5_N interpretations, WP_249925928.1 function, complete phage breadth, molecular output, and rule-level DefenseFinder criteria before minting narrower DS-42 mechanism children. kind: KNOWLEDGE_GAP status: OPEN rationale: DeWeirdt et al. support DS-42 as the defensive PRO1 transcriptional unit and final Science Tables S6/S7/S8 map it to three product accessions, a Bas1 phage readout, display name DS-42, a high-probability MBL hydrolase HHpred row, and a moderate-probability CHS5_N/Dimerization HHpred row. The pinned DefenseFinder HMM inventory records three DS-42 custom profile rows. The pinned rules table has no DS-42 row, and the first-pass record does not resolve native host breadth, complete phage breadth, direct profile-to-protein correspondence, component activities, molecular output, or endogenous DS-42 activity. evidence: - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: DeWeirdt et al. name validated TUs as DSs. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "PRO1\tNZ_QOXO01000016.1\tGCF_003334005.1\t-\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t661\t3061\tMBL fold metallo-hydrolase, hypothetical protein,\ \ hypothetical protein\tWP_001198055.1, WP_001024069.1, WP_249925928.1\t4.870544869418898\t\ 6.906754778648663\tTrue\tTrue\tPredicted novel defense gene\tDS-42" notes: The final Science supplementary Table S6 maps working_id PRO1 to DS_name DS-42, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 661-3061 with product accessions WP_001198055.1, WP_001024069.1, and WP_249925928.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tPRO1\t24-04-13\t\ 24-04-13_PRO1_CBT2_AAA4_TMRA.png\t5\t4\tY\t400000\t1.0969100130080565\t\tTrue\t\ \tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports a PRO1 assay row with a Bas1 phage readout and a -log(EOP) value of 1.097. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\tDS-42\tTrue" notes: The final Science supplementary Table S8 maps PRO1 to replicated display name DS-42. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\t3.0\t363.0\tWP_001198055.1\tMBL hydrolase\tcd07731\tComA-like_MBL-fold;\ \ Competence protein ComA, ComEC and related proteins\thhpred_9048500.hhr\t\ 12.0\t251.0\t0.998\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a high-probability MBL hydrolase HHpred hit for WP_001198055.1 in PRO1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "PRO1\t2.0\t190.0\tWP_001024069.1\tDimerization\tPF16892.9\tCHS5_N ;\ \ Chitin biosynthesis protein CHS5 N-terminus\thhpred_3514574.hhr\t108.0\t166.0\t\ 0.7787\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a moderate-probability CHS5_N/Dimerization HHpred hit for WP_001024069.1 in PRO1. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| DS-42 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | ' notes: The pinned DefenseFinder article registry maps the DS-42 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42A | | DS-42 | Custom | 70 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42A as a custom DS-42 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42B | | DS-42 | Custom | 20 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42B as a custom DS-42 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-42__DS-42C | | DS-42 | Custom | 200 |' notes: The pinned DefenseFinder HMM inventory records DS-42__DS-42C as a custom DS-42 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv notes: The pinned DefenseFinder rules table does not list DS-42, leaving rule-level detection criteria unresolved. attaches_to: - causal_graphs#ds_42_locus_reduces_phage_plaquing posed_by: codex posed_date: '2026-09-29' curation_history: - timestamp: '2026-09-29T13:30:52Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted DS-42 system as a DOI-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, history, or prior proposal record; kept the graph at PRO1 transcriptional-unit level because component activities and rule rows remain unresolved, and proposals/metpo_traitmech_v341 reserves the replacement placeholder. llm_assisted: true - timestamp: '2026-09-29T13:30:53Z' curator: codex action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP changes: Reviewed DS-42 system canonical_examples and left them empty because DeWeirdt et al. directly support cloned PRO1 assays in E. coli MG1655 and a DefenseFinder DS-42 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-42 activity. No paid research was used. llm_assisted: true