identifier: traitmech:000441
label: DS-18 system
definition: A phage defense system in which an organism possesses the single-gene
  DefensePredictor-discovered system 18 locus cataloged as working transcriptional
  unit 6602 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-18
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: '6602'
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: DS-18__DS-18
  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: "6602\tNZ_QOWV01000002.1\tGCF_003334785.1\t-\tTrue\tFalse\tFalse\tTrue\t\
    DefensePredictor hits\t550816\t551577\thypothetical protein\tWP_021529611.1\t\
    11.52849398343986\t1.909829572490831\tTrue\tTrue\tRemote defense homolog\tDS-18"
  notes: The final Science supplementary Table S6 maps working_id 6602 to DS_name
    DS-18, marks the cloned transcriptional unit as defensive, and records NZ_QOWV01000002.1
    positions 550816-551577 with product accession WP_021529611.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Candy\t6.2\tpLAND\t24-07-17_AAA2_VPUS_VAME_EV.png\t50000000\t6602\t24-07-24\t\
    24-07-24_6602_TRNA_SC24_2CMP.png\t2\t10\t\t1000\t4.698970004336019\t\t\tTrue\t\
    LB\t37"
  notes: The final Science supplementary Table S7 reports a 6602 assay row with a
    Candy phage readout and a -log(EOP) value of 4.699.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "6602.0\tDS-18\tTrue"
  notes: The final Science supplementary Table S8 maps working identifier 6602 to
    replicated display name DS-18.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "6602\t1.0\t253.0\tWP_021529611.1\tPDDEXK\tPF15516.11\tBpuSI_N ; BpuSI\
    \ N-terminal domain\thhpred_6067831.hhr\t99.0\t197.0\t0.9417\t2024-07-28 00:00:00\t\
    54-56\t41.0"
  notes: The final Science supplementary Table S8 reports a PDDEXK HHpred hit for
    WP_021529611.1 in 6602.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: '| DS-18 | 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-18 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-18__DS-18                                     |                                                  |
    DS-18                  | Custom                  | 30     |'
  notes: The pinned DefenseFinder HMM inventory records DS-18__DS-18 as a custom DS-18
    profile.
causal_graphs:
- graph_id: ds_18_locus_reduces_phage_plaquing
  title: DS-18 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the single-gene DS-18 locus
    to reduced bacteriophage plaquing without resolving DS-18 component function or
    molecular output.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-18 as the validated 6602 transcriptional unit
    with one product accession, one PDDEXK HHpred-domain row, and one DefenseFinder
    DS-18 profile row. It does not assert native host breadth, exact profile-to-protein
    correspondence, DS-18 molecular activity, trigger, substrate, phage breadth, or
    DefenseFinder rule-level detection criteria.
  nodes:
  - node_id: ds_18_locus
    label: DS-18 locus
    node_type: GENETIC_ELEMENT
    description: A single-gene DefensePredictor-discovered system 18 locus represented
      in the pinned DefenseFinder HMM inventory by one DS-18 custom profile.
  - node_id: reduced_phage_plaquing
    label: reduced bacteriophage plaquing
    node_type: BIOLOGICAL_PROCESS
    description: Reduced bacteriophage plaquing in cells carrying cloned 6602.
  - node_id: ds_18_system_trait
    label: DS-18 system
    node_type: TRAIT
    grounding: traitmech:000441
    description: Possession of a genome-encoded DS-18 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_18_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-18/6602 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: "6602\tNZ_QOWV01000002.1\tGCF_003334785.1\t-\tTrue\tFalse\tFalse\t\
        True\tDefensePredictor hits\t550816\t551577\thypothetical protein\tWP_021529611.1\t\
        11.52849398343986\t1.909829572490831\tTrue\tTrue\tRemote defense homolog\t\
        DS-18"
      notes: The final Science supplementary Table S6 maps working_id 6602 to DS_name
        DS-18, marks the cloned transcriptional unit as defensive, and records NZ_QOWV01000002.1
        positions 550816-551577 with product accession WP_021529611.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Candy\t6.2\tpLAND\t24-07-17_AAA2_VPUS_VAME_EV.png\t50000000\t6602\t\
        24-07-24\t24-07-24_6602_TRNA_SC24_2CMP.png\t2\t10\t\t1000\t4.698970004336019\t\
        \t\tTrue\tLB\t37"
      notes: The final Science supplementary Table S7 reports a 6602 assay row with
        a Candy phage readout and a -log(EOP) value of 4.699.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "6602.0\tDS-18\tTrue"
      notes: The final Science supplementary Table S8 maps working identifier 6602
        to replicated display name DS-18.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| DS-18__DS-18                                     |                                                  |
        DS-18                  | Custom                  | 30     |'
      notes: The pinned DefenseFinder HMM inventory records DS-18__DS-18 as a custom
        DS-18 profile.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_18_system_trait
    description: DS-18-mediated phage plaquing reduction realizes the DS-18 system
      trait.
    evidence:
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "6602\tNZ_QOWV01000002.1\tGCF_003334785.1\t-\tTrue\tFalse\tFalse\t\
        True\tDefensePredictor hits\t550816\t551577\thypothetical protein\tWP_021529611.1\t\
        11.52849398343986\t1.909829572490831\tTrue\tTrue\tRemote defense homolog\t\
        DS-18"
      notes: The final Science supplementary Table S6 maps working_id 6602 to DS_name
        DS-18, marks the cloned transcriptional unit as defensive, and records NZ_QOWV01000002.1
        positions 550816-551577 with product accession WP_021529611.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Candy\t6.2\tpLAND\t24-07-17_AAA2_VPUS_VAME_EV.png\t50000000\t6602\t\
        24-07-24\t24-07-24_6602_TRNA_SC24_2CMP.png\t2\t10\t\t1000\t4.698970004336019\t\
        \t\tTrue\tLB\t37"
      notes: The final Science supplementary Table S7 reports a 6602 assay row with
        a Candy phage readout and a -log(EOP) value of 4.699.
    - 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_18_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-18 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-18 | 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-18 source key to
        the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has
        since been published in Science.
discussions:
- discussion_id: ds-18-defensefinder-model-gap
  prompt: Resolve DS-18 native host breadth, exact profile-to-protein mapping, component
    chemistry, sensitive-phage breadth, molecular output, and rule-level DefenseFinder
    criteria before minting narrower DS-18 mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-18 as the defensive 6602 transcriptional unit
    and final Science Tables S6/S7/S8 map it to product accession WP_021529611.1,
    a Candy phage readout, display name DS-18, and a PDDEXK HHpred row. The pinned
    DefenseFinder HMM inventory records one DS-18 custom profile row. The pinned rules
    table has no DS-18 row, and the first-pass record does not resolve native host
    breadth, phage breadth, direct profile-to-protein correspondence, PDDEXK nuclease
    activity, molecular output, or endogenous DS-18 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: "6602\tNZ_QOWV01000002.1\tGCF_003334785.1\t-\tTrue\tFalse\tFalse\tTrue\t\
      DefensePredictor hits\t550816\t551577\thypothetical protein\tWP_021529611.1\t\
      11.52849398343986\t1.909829572490831\tTrue\tTrue\tRemote defense homolog\tDS-18"
    notes: The final Science supplementary Table S6 maps working_id 6602 to DS_name
      DS-18, marks the cloned transcriptional unit as defensive, and records NZ_QOWV01000002.1
      positions 550816-551577 with product accession WP_021529611.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Candy\t6.2\tpLAND\t24-07-17_AAA2_VPUS_VAME_EV.png\t50000000\t6602\t\
      24-07-24\t24-07-24_6602_TRNA_SC24_2CMP.png\t2\t10\t\t1000\t4.698970004336019\t\
      \t\tTrue\tLB\t37"
    notes: The final Science supplementary Table S7 reports a 6602 assay row with
      a Candy phage readout and a -log(EOP) value of 4.699.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "6602.0\tDS-18\tTrue"
    notes: The final Science supplementary Table S8 maps working identifier 6602 to
      replicated display name DS-18.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "6602\t1.0\t253.0\tWP_021529611.1\tPDDEXK\tPF15516.11\tBpuSI_N ; BpuSI\
      \ N-terminal domain\thhpred_6067831.hhr\t99.0\t197.0\t0.9417\t2024-07-28 00:00:00\t\
      54-56\t41.0"
    notes: The final Science supplementary Table S8 reports a PDDEXK HHpred hit for
      WP_021529611.1 in 6602.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    snippet: '| DS-18 | 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-18 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-18__DS-18                                     |                                                  |
      DS-18                  | Custom                  | 30     |'
    notes: The pinned DefenseFinder HMM inventory records DS-18__DS-18 as a custom
      DS-18 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table does not list DS-18, leaving rule-level
      detection criteria unresolved.
  attaches_to:
  - causal_graphs#ds_18_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-28'
curation_history:
- timestamp: '2026-09-28T18:54:30Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-18 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 6602 transcriptional-unit
    level because PDDEXK chemistry and rule rows remain unresolved, and proposals/metpo_traitmech_v318
    reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-28T18:54:31Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-18 system canonical_examples and left them empty because DeWeirdt
    et al. directly support cloned 6602 assays in E. coli MG1655 and a DefenseFinder
    DS-18 model, but not a direct named native microbial isolate exemplar with experimentally
    verified endogenous DS-18 activity. No paid research was used.
  llm_assisted: true