identifier: traitmech:000462
label: DS-40 system
definition: A phage defense system in which an organism possesses the single-gene
  DefensePredictor-discovered system 40 locus cataloged as working transcriptional
  unit D295 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-40
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: D295
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: DS-40__DS-40
  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: "D295\tNZ_QOYF01000088.1\tGCF_003334585.1\t+\tTrue\tFalse\tTrue\tTrue\t\
    DefensePredictor hits\t10328\t11263\thypothetical protein\tWP_097419291.1\t4.659671153870749\t\
    1.141745659485685\tTrue\tTrue\tPredicted novel defense gene\tDS-40"
  notes: The final Science supplementary Table S6 maps working_id D295 to DS_name
    DS-40, marks the cloned transcriptional unit as defensive, and records NZ_QOYF01000088.1
    positions 10328-11263 with product accession WP_097419291.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas26\t2.2\tpLAND\t24-03-12_EV.png\t2400000000\tD295\t24-03-14\t24-03-14_RED5_D295_6236_D932.png\t\
    3\t100\tY\t100000\t4.380211241711606\t\tTrue\t\tLB\t37"
  notes: The final Science supplementary Table S7 Systems sheet reports a D295 assay
    row with a Bas26 phage readout and a -log(EOP) value of 4.380.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "D295\tDS-40\tTrue"
  notes: The final Science supplementary Table S8 maps D295 to replicated display
    name DS-40.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "D295\t1.0\t311.0\tWP_097419291.1\tDUF6680\tPF20385.2\tDUF6680 ; Family\
    \ of unknown function (DUF6680)\thhpred_5944942.hhr\t27.0\t238.0\t0.7883\t2024-04-15\
    \ 00:00:00\t\t"
  notes: The final Science supplementary Table S8 reports a moderate-probability DUF6680
    HHpred hit for WP_097419291.1 in D295.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: '| DS-40 | 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-40 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-40__DS-40                                     |                                                  |
    DS-40                  | Custom                  | 180    |'
  notes: The pinned DefenseFinder HMM inventory records DS-40__DS-40 as a custom DS-40
    profile.
causal_graphs:
- graph_id: ds_40_locus_reduces_phage_plaquing
  title: DS-40 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the single-gene DS-40 locus
    to reduced bacteriophage plaquing without resolving DS-40 component function or
    molecular output.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-40 as the validated D295 transcriptional unit
    with one product accession, one moderate-probability DUF6680 HHpred row for WP_097419291.1,
    and one DefenseFinder DS-40 profile row. It does not assert exact profile-to-protein
    correspondence, DUF6680 activity, native host breadth, DS-40 molecular output,
    complete phage breadth, or DefenseFinder rule-level detection criteria.
  nodes:
  - node_id: ds_40_locus
    label: DS-40 locus
    node_type: GENETIC_ELEMENT
    description: A single-gene DefensePredictor-discovered system 40 locus represented
      in the pinned DefenseFinder HMM inventory by one DS-40 custom profile.
  - node_id: reduced_phage_plaquing
    label: reduced bacteriophage plaquing
    node_type: BIOLOGICAL_PROCESS
    description: Reduced bacteriophage plaquing in cells carrying cloned D295.
  - node_id: ds_40_system_trait
    label: DS-40 system
    node_type: TRAIT
    grounding: traitmech:000462
    description: Possession of a genome-encoded DS-40 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_40_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-40/D295 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: "D295\tNZ_QOYF01000088.1\tGCF_003334585.1\t+\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t10328\t11263\thypothetical protein\tWP_097419291.1\t\
        4.659671153870749\t1.141745659485685\tTrue\tTrue\tPredicted novel defense\
        \ gene\tDS-40"
      notes: The final Science supplementary Table S6 maps working_id D295 to DS_name
        DS-40, marks the cloned transcriptional unit as defensive, and records NZ_QOYF01000088.1
        positions 10328-11263 with product accession WP_097419291.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas26\t2.2\tpLAND\t24-03-12_EV.png\t2400000000\tD295\t24-03-14\t24-03-14_RED5_D295_6236_D932.png\t\
        3\t100\tY\t100000\t4.380211241711606\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports a D295
        assay row with a Bas26 phage readout and a -log(EOP) value of 4.380.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "D295\tDS-40\tTrue"
      notes: The final Science supplementary Table S8 maps D295 to replicated display
        name DS-40.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "D295\t1.0\t311.0\tWP_097419291.1\tDUF6680\tPF20385.2\tDUF6680 ; Family\
        \ of unknown function (DUF6680)\thhpred_5944942.hhr\t27.0\t238.0\t0.7883\t\
        2024-04-15 00:00:00\t\t"
      notes: The final Science supplementary Table S8 reports a moderate-probability
        DUF6680 HHpred hit for WP_097419291.1 in D295.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| DS-40__DS-40                                     |                                                  |
        DS-40                  | Custom                  | 180    |'
      notes: The pinned DefenseFinder HMM inventory records DS-40__DS-40 as a custom
        DS-40 profile.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_40_system_trait
    description: DS-40-mediated phage plaquing reduction realizes the DS-40 system
      trait.
    evidence:
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "D295\tNZ_QOYF01000088.1\tGCF_003334585.1\t+\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t10328\t11263\thypothetical protein\tWP_097419291.1\t\
        4.659671153870749\t1.141745659485685\tTrue\tTrue\tPredicted novel defense\
        \ gene\tDS-40"
      notes: The final Science supplementary Table S6 maps working_id D295 to DS_name
        DS-40, marks the cloned transcriptional unit as defensive, and records NZ_QOYF01000088.1
        positions 10328-11263 with product accession WP_097419291.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas26\t2.2\tpLAND\t24-03-12_EV.png\t2400000000\tD295\t24-03-14\t24-03-14_RED5_D295_6236_D932.png\t\
        3\t100\tY\t100000\t4.380211241711606\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports a D295
        assay row with a Bas26 phage readout and a -log(EOP) value of 4.380.
    - 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_40_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-40 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-40 | 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-40 source key to
        the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has
        since been published in Science.
discussions:
- discussion_id: ds-40-defensefinder-model-gap
  prompt: Resolve DS-40 native host breadth, exact component activity, profile-to-protein
    mapping, DUF6680 interpretation, complete phage breadth, molecular output, and
    rule-level DefenseFinder criteria before minting narrower DS-40 mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-40 as the defensive D295 transcriptional unit
    and final Science Tables S6/S7/S8 map it to one product accession, a Bas26 phage
    readout, display name DS-40, and a moderate-probability DUF6680 HHpred row. The
    pinned DefenseFinder HMM inventory records one DS-40 custom profile row. The pinned
    rules table has no DS-40 row, and the first-pass record does not resolve native
    host breadth, complete phage breadth, direct profile-to-protein correspondence,
    DUF6680 activity, molecular output, or endogenous DS-40 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: "D295\tNZ_QOYF01000088.1\tGCF_003334585.1\t+\tTrue\tFalse\tTrue\tTrue\t\
      DefensePredictor hits\t10328\t11263\thypothetical protein\tWP_097419291.1\t\
      4.659671153870749\t1.141745659485685\tTrue\tTrue\tPredicted novel defense gene\t\
      DS-40"
    notes: The final Science supplementary Table S6 maps working_id D295 to DS_name
      DS-40, marks the cloned transcriptional unit as defensive, and records NZ_QOYF01000088.1
      positions 10328-11263 with product accession WP_097419291.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas26\t2.2\tpLAND\t24-03-12_EV.png\t2400000000\tD295\t24-03-14\t24-03-14_RED5_D295_6236_D932.png\t\
      3\t100\tY\t100000\t4.380211241711606\t\tTrue\t\tLB\t37"
    notes: The final Science supplementary Table S7 Systems sheet reports a D295 assay
      row with a Bas26 phage readout and a -log(EOP) value of 4.380.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "D295\tDS-40\tTrue"
    notes: The final Science supplementary Table S8 maps D295 to replicated display
      name DS-40.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "D295\t1.0\t311.0\tWP_097419291.1\tDUF6680\tPF20385.2\tDUF6680 ; Family\
      \ of unknown function (DUF6680)\thhpred_5944942.hhr\t27.0\t238.0\t0.7883\t2024-04-15\
      \ 00:00:00\t\t"
    notes: The final Science supplementary Table S8 reports a moderate-probability
      DUF6680 HHpred hit for WP_097419291.1 in D295.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    snippet: '| DS-40 | 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-40 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-40__DS-40                                     |                                                  |
      DS-40                  | Custom                  | 180    |'
    notes: The pinned DefenseFinder HMM inventory records DS-40__DS-40 as a custom
      DS-40 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table does not list DS-40, leaving rule-level
      detection criteria unresolved.
  attaches_to:
  - causal_graphs#ds_40_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-29'
curation_history:
- timestamp: '2026-09-29T12:02:12Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-40 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 D295 transcriptional-unit
    level because DUF6680 activity and rule rows remain unresolved, and proposals/metpo_traitmech_v339
    reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-29T12:02:13Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-40 system canonical_examples and left them empty because DeWeirdt
    et al. directly support cloned D295 assays in E. coli MG1655 and a DefenseFinder
    DS-40 model, but not a direct named native microbial isolate exemplar with experimentally
    verified endogenous DS-40 activity. No paid research was used.
  llm_assisted: true