identifier: traitmech:000436
label: DS-12 system
definition: A phage defense system in which an organism possesses the two-gene DefensePredictor-discovered
  system 12 locus cataloged as working transcriptional unit PD3A 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-12
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: PD3A
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: DS-12__DS-12B
  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: "PD3A\tNZ_RRVF01000002.1\tGCF_003886115.1\t-\tTrue\tFalse\tTrue\tTrue\t\
    DefensePredictor hits\t104144\t108678\trestriction endonuclease, AAA family ATPase\t\
    WP_059339975.1, WP_064766070.1\t14.31811904122612\t6.906754778648663\tTrue\tTrue\t\
    Remote defense homolog\tDS-12"
  notes: The final Science supplementary Table S6 maps working_id PD3A to DS_name
    DS-12, marks the cloned transcriptional unit as defensive, and records NZ_RRVF01000002.1
    positions 104144-108678 with product accessions WP_059339975.1 and WP_064766070.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas25\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t200000000\tPD3A\t24-05-17\t24-05-17_VAME_AAA1_PD3A_PDP7.png\t\
    3\t2\t\t2000\t5\t\tTrue\t\tLB\t37"
  notes: The final Science supplementary Table S7 reports a PD3A assay row with a
    Bas25 phage readout and a -log(EOP) value of 5.0.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "PD3A\tDS-12\tTrue"
  notes: The final Science supplementary Table S8 maps PD3A to replicated display
    name DS-12.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "PD3A\t1.0\t750.0\tWP_064766070.1\tABC ATPase\t3ZGX_B\tCHROMOSOME PARTITION\
    \ PROTEIN SMC; CELL CYCLE; 3.4A {BACILLUS SUBTILIS}\thhpred_5638008.hhr\t495.0\t\
    581.0\t1.0\t2024-05-21 00:00:00"
  notes: The final Science supplementary Table S8 reports an ABC ATPase HHpred hit
    for WP_064766070.1 in PD3A.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "PD3A\t2.0\t761.0\tWP_059339975.1\tPDDEXK\tcd22335\tMspjI-like; Modification-dependent\
    \ restriction endonuclease MspjI and similar endonucleases.\thhpred_5143119.hhr\t\
    4.0\t129.0\t0.98\t2024-07-30 00:00:00\t335-337\t322.0"
  notes: The final Science supplementary Table S8 reports a PDDEXK HHpred hit for
    WP_059339975.1 in PD3A.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "PD3A\t2.0\t761.0\tWP_059339975.1\tNACHT\tPF20720.2\tnSTAND3 ; Novel STAND\
    \ NTPase 3\thhpred_5143119.hhr\t174.0\t327.0\t0.99\t2024-07-30 00:00:00"
  notes: The final Science supplementary Table S8 reports a NACHT HHpred hit for WP_059339975.1
    in PD3A.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: '| DS-12B | 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-12B 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-12__DS-12B                                    |                                                  |
    DS-12                  | Custom                  | 100    |'
  notes: The pinned DefenseFinder HMM inventory records DS-12__DS-12B as a custom
    DS-12 profile.
causal_graphs:
- graph_id: ds_12_locus_reduces_phage_plaquing
  title: DS-12 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the two-gene DS-12 locus to
    reduced bacteriophage plaquing without resolving DS-12 component function or effector
    activity.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-12 as the validated PD3A transcriptional unit
    with two product accessions, final Table S8 ABC ATPase, PDDEXK, and NACHT HHpred-domain
    rows, and one DefenseFinder DS-12B profile row. It does not assert native host
    breadth, DS-12A model coverage, exact DS-12B profile-to-protein correspondence,
    the direct viral trigger or substrate, exact ABC ATPase or nuclease chemistry,
    phage target breadth, or DefenseFinder rule-level detection criteria.
  nodes:
  - node_id: ds_12_locus
    label: DS-12 locus
    node_type: GENETIC_ELEMENT
    description: A two-gene DefensePredictor-discovered system locus represented in
      the pinned DefenseFinder HMM inventory by one DS-12B custom profile.
  - node_id: reduced_phage_plaquing
    label: reduced bacteriophage plaquing
    node_type: BIOLOGICAL_PROCESS
    description: Reduced bacteriophage plaquing by cells carrying cloned PD3A.
  - node_id: ds_12_system_trait
    label: DS-12 system
    node_type: TRAIT
    grounding: traitmech:000436
    description: Possession of a genome-encoded DS-12 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_12_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-12/PD3A locus contributes to reduced bacteriophage plaquing
      when plasmid expressed.
    evidence:
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "PD3A\tNZ_RRVF01000002.1\tGCF_003886115.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t104144\t108678\trestriction endonuclease, AAA family\
        \ ATPase\tWP_059339975.1, WP_064766070.1\t14.31811904122612\t6.906754778648663\t\
        True\tTrue\tRemote defense homolog\tDS-12"
      notes: The final Science supplementary Table S6 maps working_id PD3A to DS_name
        DS-12, marks the cloned transcriptional unit as defensive, and records NZ_RRVF01000002.1
        positions 104144-108678 with product accessions WP_059339975.1 and WP_064766070.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas25\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t200000000\tPD3A\t24-05-17\t\
        24-05-17_VAME_AAA1_PD3A_PDP7.png\t3\t2\t\t2000\t5\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports a PD3A assay row with
        a Bas25 phage readout and a -log(EOP) value of 5.0.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_12_system_trait
    description: DS-12-mediated phage plaquing reduction realizes the DS-12 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 each validated transcriptional unit as a DefensePredictor
        discovered system.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "PD3A\tNZ_RRVF01000002.1\tGCF_003886115.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t104144\t108678\trestriction endonuclease, AAA family\
        \ ATPase\tWP_059339975.1, WP_064766070.1\t14.31811904122612\t6.906754778648663\t\
        True\tTrue\tRemote defense homolog\tDS-12"
      notes: The final Science supplementary Table S6 maps working_id PD3A to DS_name
        DS-12, marks the cloned transcriptional unit as defensive, and records NZ_RRVF01000002.1
        positions 104144-108678 with product accessions WP_059339975.1 and WP_064766070.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas25\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t200000000\tPD3A\t24-05-17\t\
        24-05-17_VAME_AAA1_PD3A_PDP7.png\t3\t2\t\t2000\t5\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports a PD3A assay row with
        a Bas25 phage readout and a -log(EOP) value of 5.0.
  - subject: ds_12_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-12 system possession is a phage-defense-system trait.
    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. validate DSs as anti-phage systems.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
      snippet: '| DS-12B | 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-12B source key
        to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which
        has since been published in Science.
discussions:
- discussion_id: ds-12-defensefinder-model-gap
  prompt: Resolve DS-12 native host breadth, DS-12A model coverage, DS-12B profile-to-protein
    mapping, sensitive-phage breadth, direct viral trigger or substrate, exact ABC
    ATPase and PDDEXK/nSTAND nuclease chemistry, and rule-level detection criteria
    before minting narrower DS-12 mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-12 as the defensive PD3A transcriptional unit
    that reduced Bas25 plaquing when cloned in E. coli MG1655, and the final Table
    S8 HHpred sheet reports ABC ATPase, PDDEXK, and NACHT hits across the two PD3A
    products. The pinned DefenseFinder HMM inventory records one DS-12B profile row,
    the pinned article registry names DS-12B rather than DS-12, the pinned rules table
    has no DS-12 row, and the first-pass record does not resolve native host breadth,
    DS-12A model coverage, exact profile-to-protein correspondence, direct ATPase
    or nuclease activity, phage target breadth, or endogenous DS-12 activity.
  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. validate predicted transcriptional units by measuring plaquing
      relative to an empty vector control strain.
  - 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: "PD3A\tNZ_RRVF01000002.1\tGCF_003886115.1\t-\tTrue\tFalse\tTrue\tTrue\t\
      DefensePredictor hits\t104144\t108678\trestriction endonuclease, AAA family\
      \ ATPase\tWP_059339975.1, WP_064766070.1\t14.31811904122612\t6.906754778648663\t\
      True\tTrue\tRemote defense homolog\tDS-12"
    notes: The final Science supplementary Table S6 maps working_id PD3A to DS_name
      DS-12, marks the cloned transcriptional unit as defensive, and records NZ_RRVF01000002.1
      positions 104144-108678 with product accessions WP_059339975.1 and WP_064766070.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas25\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t200000000\tPD3A\t24-05-17\t\
      24-05-17_VAME_AAA1_PD3A_PDP7.png\t3\t2\t\t2000\t5\t\tTrue\t\tLB\t37"
    notes: The final Science supplementary Table S7 reports a PD3A assay row with
      a Bas25 phage readout and a -log(EOP) value of 5.0.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "PD3A\tDS-12\tTrue"
    notes: The final Science supplementary Table S8 maps PD3A to replicated display
      name DS-12.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "PD3A\t1.0\t750.0\tWP_064766070.1\tABC ATPase\t3ZGX_B\tCHROMOSOME PARTITION\
      \ PROTEIN SMC; CELL CYCLE; 3.4A {BACILLUS SUBTILIS}\thhpred_5638008.hhr\t495.0\t\
      581.0\t1.0\t2024-05-21 00:00:00"
    notes: The final Science supplementary Table S8 reports an ABC ATPase HHpred hit
      for WP_064766070.1 in PD3A.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "PD3A\t2.0\t761.0\tWP_059339975.1\tPDDEXK\tcd22335\tMspjI-like; Modification-dependent\
      \ restriction endonuclease MspjI and similar endonucleases.\thhpred_5143119.hhr\t\
      4.0\t129.0\t0.98\t2024-07-30 00:00:00\t335-337\t322.0"
    notes: The final Science supplementary Table S8 reports a PDDEXK HHpred hit for
      WP_059339975.1 in PD3A.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "PD3A\t2.0\t761.0\tWP_059339975.1\tNACHT\tPF20720.2\tnSTAND3 ; Novel\
      \ STAND NTPase 3\thhpred_5143119.hhr\t174.0\t327.0\t0.99\t2024-07-30 00:00:00"
    notes: The final Science supplementary Table S8 reports a NACHT HHpred hit for
      WP_059339975.1 in PD3A.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    snippet: '| DS-12B | 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-12B 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-12__DS-12B                                    |                                                  |
      DS-12                  | Custom                  | 100    |'
    notes: The pinned DefenseFinder HMM inventory records DS-12__DS-12B as a custom
      DS-12 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table does not list DS-12, DS-12B, PD3A,
      or the PD3A product accessions, leaving complete component coverage and rule-level
      detection criteria unresolved.
  attaches_to:
  - causal_graphs#ds_12_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-28'
curation_history:
- timestamp: '2026-09-28T15:20:46Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-12 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 cloned PD3A transcriptional-unit
    level because the pinned DefenseFinder DS-12B HMM row leaves DS-12A coverage unresolved
    and proposals/metpo_traitmech_v313 reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-28T15:20:47Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-12 system canonical_examples and left them empty because DeWeirdt
    et al. support cloned PD3A plaquing assays in E. coli MG1655 plus a partial DefenseFinder
    DS-12B model, but not a direct named native microbial isolate exemplar with experimentally
    verified endogenous DS-12 activity. No paid research was used.
  llm_assisted: true