identifier: traitmech:000438
label: DS-15 system
definition: A phage defense system in which an organism possesses the three-gene DefensePredictor-discovered
  system 15 locus cataloged as working transcriptional unit AAA1 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-15
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: AAA1
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: DS-15__DS-15A
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: DS-15__DS-15B
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: DS-15__DS-15C
  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: "AAA1\tNZ_QOXE01000046.1\tGCF_003334165.1\t-\tTrue\tFalse\tTrue\tTrue\t\
    DefensePredictor hits\t29629\t31530\thypothetical protein, hypothetical protein,\
    \ AAA family ATPase\tWP_000957441.1, WP_060581740.1, WP_001619161.1\t11.46862191778244\t\
    2.030866871531279\tTrue\tTrue\tPredicted novel defense gene\tDS-15"
  notes: The final Science supplementary Table S6 maps working_id AAA1 to DS_name
    DS-15, marks the cloned transcriptional unit as defensive, and records NZ_QOXE01000046.1
    positions 29629-31530 with product accessions WP_000957441.1, WP_060581740.1,
    and WP_001619161.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t5000000\tAAA1\t24-05-17\t24-05-17_VAME_AAA1_PD3A_PDP7.png\t\
    2\t100\t\t10000\t2.6989700043360187\t\tTrue\t\tLB\t37"
  notes: The final Science supplementary Table S7 reports an AAA1 assay row with a
    Bas1 phage readout and a -log(EOP) value of 2.699.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "AAA1\tDS-15\tTrue"
  notes: The final Science supplementary Table S8 maps AAA1 to replicated display
    name DS-15.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "AAA1\t1.0\t281.0\tWP_001619161.1\tMinD ATPase\tSCOP_d1hyqa_\tc.37.1.10\
    \ (A:) Cell division regulator MinD {Archaeoglobus fulgidus [TaxId: 2234]} | CLASS:\
    \ Alpha and beta proteins (a/b), FOLD: P-loop containing nucleoside triphosphate\
    \ hydrolases, SUPFAM: P-loop containing nucleoside triphosphate hydrolases, FAM:\
    \ Nitrogenase iron protein-like\thhpred_6736485.hhr\t3.0\t268.0\t1.0\t2024-07-29\
    \ 00:00:00"
  notes: The final Science supplementary Table S8 reports a MinD ATPase HHpred hit
    for WP_001619161.1 in AAA1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "AAA1\t3.0\t221.0\tWP_000957441.1\tDUF6988\tPF22491.1\tDUF6988 ; Family\
    \ of unknown function (DUF6988)\thhpred_7907160.hhr\t68.0\t144.0\t0.94\t2024-07-29\
    \ 00:00:00"
  notes: The final Science supplementary Table S8 reports a DUF6988 HHpred hit for
    WP_000957441.1 in AAA1.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: '| DS-15 | 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-15 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-15__DS-15A                                    |                                                  |
    DS-15                  | Custom                  | 300    |'
  notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15A as a custom
    DS-15 profile.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| DS-15__DS-15B                                    |                                                  |
    DS-15                  | Custom                  | 20     |'
  notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15B as a custom
    DS-15 profile.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| DS-15__DS-15C                                    |                                                  |
    DS-15                  | Custom                  | 20     |'
  notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15C as a custom
    DS-15 profile.
causal_graphs:
- graph_id: ds_15_locus_reduces_phage_plaquing
  title: DS-15 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the three-gene DS-15 locus
    to reduced bacteriophage plaquing without resolving DS-15 component function or
    effector activity.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-15 as the validated AAA1 transcriptional unit
    with three product accessions, final Table S8 MinD ATPase and DUF6988 HHpred-domain
    rows, and three DefenseFinder DS-15 profile rows. It does not assert native host
    breadth, exact profile-to-protein correspondence, the direct viral trigger or
    substrate, exact AAA family ATPase or DUF6988 chemistry, phage target breadth,
    or DefenseFinder rule-level detection criteria.
  nodes:
  - node_id: ds_15_locus
    label: DS-15 locus
    node_type: GENETIC_ELEMENT
    description: A three-gene DefensePredictor-discovered system locus represented
      in the pinned DefenseFinder HMM inventory by DS-15A, DS-15B, and DS-15C custom
      profiles.
  - node_id: reduced_phage_plaquing
    label: reduced bacteriophage plaquing
    node_type: BIOLOGICAL_PROCESS
    description: Reduced efficiency of plaquing by bacteriophage Bas1 in cells carrying
      cloned AAA1.
  - node_id: ds_15_system_trait
    label: DS-15 system
    node_type: TRAIT
    grounding: traitmech:000438
    description: Possession of a genome-encoded DS-15 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_15_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-15/AAA1 locus contributes to reduced bacteriophage plaquing
      when plasmid expressed.
    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 validate DefensePredictor-discovered systems
        by assaying cloned transcriptional units against E. coli phages.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "AAA1\tNZ_QOXE01000046.1\tGCF_003334165.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t29629\t31530\thypothetical protein, hypothetical protein,\
        \ AAA family ATPase\tWP_000957441.1, WP_060581740.1, WP_001619161.1\t11.46862191778244\t\
        2.030866871531279\tTrue\tTrue\tPredicted novel defense gene\tDS-15"
      notes: The final Science supplementary Table S6 maps working_id AAA1 to DS_name
        DS-15, marks the cloned transcriptional unit as defensive, and records NZ_QOXE01000046.1
        positions 29629-31530 with product accessions WP_000957441.1, WP_060581740.1,
        and WP_001619161.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t5000000\tAAA1\t24-05-17\t\
        24-05-17_VAME_AAA1_PD3A_PDP7.png\t2\t100\t\t10000\t2.6989700043360187\t\t\
        True\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports an AAA1 assay row with
        a Bas1 phage readout and a -log(EOP) value of 2.699.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| DS-15__DS-15A                                    |                                                  |
        DS-15                  | Custom                  | 300    |'
      notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15A as a custom
        DS-15 profile.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| DS-15__DS-15B                                    |                                                  |
        DS-15                  | Custom                  | 20     |'
      notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15B as a custom
        DS-15 profile.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| DS-15__DS-15C                                    |                                                  |
        DS-15                  | Custom                  | 20     |'
      notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15C as a custom
        DS-15 profile.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_15_system_trait
    description: DS-15-mediated phage plaquing reduction realizes the DS-15 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: "AAA1\tNZ_QOXE01000046.1\tGCF_003334165.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t29629\t31530\thypothetical protein, hypothetical protein,\
        \ AAA family ATPase\tWP_000957441.1, WP_060581740.1, WP_001619161.1\t11.46862191778244\t\
        2.030866871531279\tTrue\tTrue\tPredicted novel defense gene\tDS-15"
      notes: The final Science supplementary Table S6 maps working_id AAA1 to DS_name
        DS-15, marks the cloned transcriptional unit as defensive, and records NZ_QOXE01000046.1
        positions 29629-31530 with product accessions WP_000957441.1, WP_060581740.1,
        and WP_001619161.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t5000000\tAAA1\t24-05-17\t\
        24-05-17_VAME_AAA1_PD3A_PDP7.png\t2\t100\t\t10000\t2.6989700043360187\t\t\
        True\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports an AAA1 assay row with
        a Bas1 phage readout and a -log(EOP) value of 2.699.
  - subject: ds_15_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-15 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-15 | 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-15 source key to
        the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has
        since been published in Science.
discussions:
- discussion_id: ds-15-defensefinder-model-gap
  prompt: Resolve DS-15 native host breadth, exact profile-to-protein mapping, DS-15A/DS-15B/DS-15C
    component activities, sensitive-phage breadth, exact AAA family ATPase and DUF6988
    chemistry, and rule-level DefenseFinder criteria before minting narrower DS-15
    mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-15 as the defensive AAA1 transcriptional unit
    that reduced Bas1 plaquing when cloned in E. coli MG1655, the final Table S8 HHpred
    sheet reports MinD ATPase and DUF6988 hits across two AAA1 products, and the pinned
    DefenseFinder HMM inventory records DS-15A, DS-15B, and DS-15C custom profile
    rows. The pinned rules table has no DS-15 row, and the first-pass record does
    not resolve native host breadth, exact profile-to-protein correspondence, direct
    ATPase or DUF6988 activity, phage target breadth, or endogenous DS-15 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: "AAA1\tNZ_QOXE01000046.1\tGCF_003334165.1\t-\tTrue\tFalse\tTrue\tTrue\t\
      DefensePredictor hits\t29629\t31530\thypothetical protein, hypothetical protein,\
      \ AAA family ATPase\tWP_000957441.1, WP_060581740.1, WP_001619161.1\t11.46862191778244\t\
      2.030866871531279\tTrue\tTrue\tPredicted novel defense gene\tDS-15"
    notes: The final Science supplementary Table S6 maps working_id AAA1 to DS_name
      DS-15, marks the cloned transcriptional unit as defensive, and records NZ_QOXE01000046.1
      positions 29629-31530 with product accessions WP_000957441.1, WP_060581740.1,
      and WP_001619161.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\t4.2\tpLAND\t24-05-17_EV_HHNH.png\t5000000\tAAA1\t24-05-17\t24-05-17_VAME_AAA1_PD3A_PDP7.png\t\
      2\t100\t\t10000\t2.6989700043360187\t\tTrue\t\tLB\t37"
    notes: The final Science supplementary Table S7 reports an AAA1 assay row with
      a Bas1 phage readout and a -log(EOP) value of 2.699.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "AAA1\tDS-15\tTrue"
    notes: The final Science supplementary Table S8 maps AAA1 to replicated display
      name DS-15.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "AAA1\t1.0\t281.0\tWP_001619161.1\tMinD ATPase\tSCOP_d1hyqa_\tc.37.1.10\
      \ (A:) Cell division regulator MinD {Archaeoglobus fulgidus [TaxId: 2234]} |\
      \ CLASS: Alpha and beta proteins (a/b), FOLD: P-loop containing nucleoside triphosphate\
      \ hydrolases, SUPFAM: P-loop containing nucleoside triphosphate hydrolases,\
      \ FAM: Nitrogenase iron protein-like\thhpred_6736485.hhr\t3.0\t268.0\t1.0\t\
      2024-07-29 00:00:00"
    notes: The final Science supplementary Table S8 reports a MinD ATPase HHpred hit
      for WP_001619161.1 in AAA1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "AAA1\t3.0\t221.0\tWP_000957441.1\tDUF6988\tPF22491.1\tDUF6988 ; Family\
      \ of unknown function (DUF6988)\thhpred_7907160.hhr\t68.0\t144.0\t0.94\t2024-07-29\
      \ 00:00:00"
    notes: The final Science supplementary Table S8 reports a DUF6988 HHpred hit for
      WP_000957441.1 in AAA1.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    snippet: '| DS-15 | 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-15 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-15__DS-15A                                    |                                                  |
      DS-15                  | Custom                  | 300    |'
    notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15A as a custom
      DS-15 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
    snippet: '| DS-15__DS-15B                                    |                                                  |
      DS-15                  | Custom                  | 20     |'
    notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15B as a custom
      DS-15 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
    snippet: '| DS-15__DS-15C                                    |                                                  |
      DS-15                  | Custom                  | 20     |'
    notes: The pinned DefenseFinder HMM inventory records DS-15__DS-15C as a custom
      DS-15 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table does not list DS-15, DS-15A, DS-15B,
      or DS-15C, leaving complete component coverage and rule-level detection criteria
      unresolved.
  attaches_to:
  - causal_graphs#ds_15_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-28'
curation_history:
- timestamp: '2026-09-28T16:50:13Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-15 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 AAA1 transcriptional-unit
    level because the pinned DefenseFinder DS-15 HMM rows are not backed by a rules
    row; proposals/metpo_traitmech_v315 reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-28T16:50:14Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-15 system canonical_examples and left them empty because DeWeirdt
    et al. support cloned AAA1 plaquing assays in E. coli MG1655 plus DefenseFinder
    DS-15 models, but not a direct named native microbial isolate exemplar with experimentally
    verified endogenous DS-15 activity. No paid research was used.
  llm_assisted: true