identifier: traitmech:000460
label: DS-38 system
definition: A phage defense system in which an organism possesses the single-gene
  DefensePredictor-discovered system 38 locus cataloged as working transcriptional
  unit HEP2 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-38
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: HEP2
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: DS-38__DS-38
  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: "HEP2\tNZ_QOYR01000034.1\tGCF_003333645.1\t-\tTrue\tFalse\tTrue\tTrue\t\
    DefensePredictor hits\t8089\t9189\thypothetical protein\tWP_001313577.1\t8.026493157403\t\
    2.649821696202418\tTrue\tTrue\tPredicted novel defense gene\tDS-38"
  notes: The final Science supplementary Table S6 maps working_id HEP2 to DS_name
    DS-38, marks the cloned transcriptional unit as defensive, and records NZ_QOYR01000034.1
    positions 8089-9189 with product accession WP_001313577.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas25\t2.2\tpLAND\t24-03-12_EV.png\t500000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
    0\t1\t\t1\t5.698970004336019\t\tTrue\t\tLB\t37"
  notes: The final Science supplementary Table S7 Systems sheet reports an HEP2 assay
    row with a Bas25 phage readout and a -log(EOP) value of 5.699.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas19\t2.2\tpLAND\t24-03-12_EV.png\t15000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
    0\t1\t\t1\t4.176091259055681\t\tTrue\t\tLB\t37"
  notes: The final Science supplementary Table S7 Systems sheet reports an HEP2 assay
    row with a Bas19 phage readout and a -log(EOP) value of 4.176.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "HEP2\tDS-38\tTrue"
  notes: The final Science supplementary Table S8 maps HEP2 to replicated display
    name DS-38.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "HEP2\t1.0\t366.0\tWP_001313577.1\tZF\t8SSU_A\tTranscriptional repressor\
    \ CTCF,LIM domain-binding protein 1; PROTEIN-DNA COMPLEX, DNA BINDING PROTEIN,\
    \ transcription factor, zinc fingers, insulator/chromatin architecture, transcription-dna\
    \ complex, TRANSCRIPTION\thhpred_7553560.hhr\t206.0\t364.0\t0.9902\t2024-04-15\
    \ 00:00:00\t\t"
  notes: The final Science supplementary Table S8 reports a high-probability zinc-finger
    HHpred hit for WP_001313577.1 in HEP2.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "HEP2\t1.0\t366.0\tWP_001313577.1\tHEPN\tPF05168.18\tHEPN ; HEPN domain\t\
    hhpred_7553560.hhr\t22.0\t153.0\t0.9662\t2024-04-15 00:00:00\t\t"
  notes: The final Science supplementary Table S8 reports a high-probability HEPN
    HHpred hit for WP_001313577.1 in HEP2.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: '| DS-38 | 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-38 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-38__DS-38                                     |                                                  |
    DS-38                  | Custom                  | 200    |'
  notes: The pinned DefenseFinder HMM inventory records DS-38__DS-38 as a custom DS-38
    profile.
causal_graphs:
- graph_id: ds_38_locus_reduces_phage_plaquing
  title: DS-38 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the single-gene DS-38 locus
    to reduced bacteriophage plaquing without resolving DS-38 component function or
    molecular output.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-38 as the validated HEP2 transcriptional unit
    with one product accession, high-probability zinc-finger and HEPN HHpred rows
    for WP_001313577.1, and one DefenseFinder DS-38 profile row. It does not assert
    exact profile-to-protein correspondence, HEPN ribonuclease activity, zinc-finger
    DNA-binding activity, native host breadth, DS-38 molecular output, complete phage
    breadth, or DefenseFinder rule-level detection criteria.
  nodes:
  - node_id: ds_38_locus
    label: DS-38 locus
    node_type: GENETIC_ELEMENT
    description: A single-gene DefensePredictor-discovered system 38 locus represented
      in the pinned DefenseFinder HMM inventory by one DS-38 custom profile.
  - node_id: reduced_phage_plaquing
    label: reduced bacteriophage plaquing
    node_type: BIOLOGICAL_PROCESS
    description: Reduced bacteriophage plaquing in cells carrying cloned HEP2.
  - node_id: ds_38_system_trait
    label: DS-38 system
    node_type: TRAIT
    grounding: traitmech:000460
    description: Possession of a genome-encoded DS-38 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_38_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-38/HEP2 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: "HEP2\tNZ_QOYR01000034.1\tGCF_003333645.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t8089\t9189\thypothetical protein\tWP_001313577.1\t\
        8.026493157403\t2.649821696202418\tTrue\tTrue\tPredicted novel defense gene\t\
        DS-38"
      notes: The final Science supplementary Table S6 maps working_id HEP2 to DS_name
        DS-38, marks the cloned transcriptional unit as defensive, and records NZ_QOYR01000034.1
        positions 8089-9189 with product accession WP_001313577.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas25\t2.2\tpLAND\t24-03-12_EV.png\t500000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
        0\t1\t\t1\t5.698970004336019\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports an HEP2
        assay row with a Bas25 phage readout and a -log(EOP) value of 5.699.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas19\t2.2\tpLAND\t24-03-12_EV.png\t15000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
        0\t1\t\t1\t4.176091259055681\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports an HEP2
        assay row with a Bas19 phage readout and a -log(EOP) value of 4.176.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "HEP2\tDS-38\tTrue"
      notes: The final Science supplementary Table S8 maps HEP2 to replicated display
        name DS-38.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "HEP2\t1.0\t366.0\tWP_001313577.1\tZF\t8SSU_A\tTranscriptional repressor\
        \ CTCF,LIM domain-binding protein 1; PROTEIN-DNA COMPLEX, DNA BINDING PROTEIN,\
        \ transcription factor, zinc fingers, insulator/chromatin architecture, transcription-dna\
        \ complex, TRANSCRIPTION\thhpred_7553560.hhr\t206.0\t364.0\t0.9902\t2024-04-15\
        \ 00:00:00\t\t"
      notes: The final Science supplementary Table S8 reports a high-probability zinc-finger
        HHpred hit for WP_001313577.1 in HEP2.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "HEP2\t1.0\t366.0\tWP_001313577.1\tHEPN\tPF05168.18\tHEPN ; HEPN domain\t\
        hhpred_7553560.hhr\t22.0\t153.0\t0.9662\t2024-04-15 00:00:00\t\t"
      notes: The final Science supplementary Table S8 reports a high-probability HEPN
        HHpred hit for WP_001313577.1 in HEP2.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
      snippet: '| DS-38__DS-38                                     |                                                  |
        DS-38                  | Custom                  | 200    |'
      notes: The pinned DefenseFinder HMM inventory records DS-38__DS-38 as a custom
        DS-38 profile.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_38_system_trait
    description: DS-38-mediated phage plaquing reduction realizes the DS-38 system
      trait.
    evidence:
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "HEP2\tNZ_QOYR01000034.1\tGCF_003333645.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t8089\t9189\thypothetical protein\tWP_001313577.1\t\
        8.026493157403\t2.649821696202418\tTrue\tTrue\tPredicted novel defense gene\t\
        DS-38"
      notes: The final Science supplementary Table S6 maps working_id HEP2 to DS_name
        DS-38, marks the cloned transcriptional unit as defensive, and records NZ_QOYR01000034.1
        positions 8089-9189 with product accession WP_001313577.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas25\t2.2\tpLAND\t24-03-12_EV.png\t500000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
        0\t1\t\t1\t5.698970004336019\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports an HEP2
        assay row with a Bas25 phage readout and a -log(EOP) value of 5.699.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas19\t2.2\tpLAND\t24-03-12_EV.png\t15000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
        0\t1\t\t1\t4.176091259055681\t\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports an HEP2
        assay row with a Bas19 phage readout and a -log(EOP) value of 4.176.
    - 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_38_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-38 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-38 | 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-38 source key to
        the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has
        since been published in Science.
discussions:
- discussion_id: ds-38-defensefinder-model-gap
  prompt: Resolve DS-38 native host breadth, exact component activity, profile-to-protein
    mapping, HEPN ribonuclease interpretation, zinc-finger DNA-binding interpretation,
    complete phage breadth, molecular output, and rule-level DefenseFinder criteria
    before minting narrower DS-38 mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-38 as the defensive HEP2 transcriptional unit
    and final Science Tables S6/S7/S8 map it to one product accession, Bas25 and Bas19
    phage readouts, display name DS-38, and high-probability HEPN and zinc-finger
    HHpred rows. The pinned DefenseFinder HMM inventory records one DS-38 custom profile
    row. The pinned rules table has no DS-38 row, and the first-pass record does not
    resolve native host breadth, complete phage breadth, direct profile-to-protein
    correspondence, HEPN ribonuclease activity, zinc-finger DNA-binding activity,
    molecular output, or endogenous DS-38 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: "HEP2\tNZ_QOYR01000034.1\tGCF_003333645.1\t-\tTrue\tFalse\tTrue\tTrue\t\
      DefensePredictor hits\t8089\t9189\thypothetical protein\tWP_001313577.1\t8.026493157403\t\
      2.649821696202418\tTrue\tTrue\tPredicted novel defense gene\tDS-38"
    notes: The final Science supplementary Table S6 maps working_id HEP2 to DS_name
      DS-38, marks the cloned transcriptional unit as defensive, and records NZ_QOYR01000034.1
      positions 8089-9189 with product accession WP_001313577.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas25\t2.2\tpLAND\t24-03-12_EV.png\t500000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
      0\t1\t\t1\t5.698970004336019\t\tTrue\t\tLB\t37"
    notes: The final Science supplementary Table S7 Systems sheet reports an HEP2
      assay row with a Bas25 phage readout and a -log(EOP) value of 5.699.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas19\t2.2\tpLAND\t24-03-12_EV.png\t15000\tHEP2\t24-03-15\t24-03-15_GPEH_HEP2_PDO1_PDP6.png\t\
      0\t1\t\t1\t4.176091259055681\t\tTrue\t\tLB\t37"
    notes: The final Science supplementary Table S7 Systems sheet reports an HEP2
      assay row with a Bas19 phage readout and a -log(EOP) value of 4.176.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "HEP2\tDS-38\tTrue"
    notes: The final Science supplementary Table S8 maps HEP2 to replicated display
      name DS-38.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "HEP2\t1.0\t366.0\tWP_001313577.1\tZF\t8SSU_A\tTranscriptional repressor\
      \ CTCF,LIM domain-binding protein 1; PROTEIN-DNA COMPLEX, DNA BINDING PROTEIN,\
      \ transcription factor, zinc fingers, insulator/chromatin architecture, transcription-dna\
      \ complex, TRANSCRIPTION\thhpred_7553560.hhr\t206.0\t364.0\t0.9902\t2024-04-15\
      \ 00:00:00\t\t"
    notes: The final Science supplementary Table S8 reports a high-probability zinc-finger
      HHpred hit for WP_001313577.1 in HEP2.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "HEP2\t1.0\t366.0\tWP_001313577.1\tHEPN\tPF05168.18\tHEPN ; HEPN domain\t\
      hhpred_7553560.hhr\t22.0\t153.0\t0.9662\t2024-04-15 00:00:00\t\t"
    notes: The final Science supplementary Table S8 reports a high-probability HEPN
      HHpred hit for WP_001313577.1 in HEP2.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    snippet: '| DS-38 | 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-38 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-38__DS-38                                     |                                                  |
      DS-38                  | Custom                  | 200    |'
    notes: The pinned DefenseFinder HMM inventory records DS-38__DS-38 as a custom
      DS-38 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table does not list DS-38, leaving rule-level
      detection criteria unresolved.
  attaches_to:
  - causal_graphs#ds_38_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-29'
curation_history:
- timestamp: '2026-09-29T10:59:36Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-38 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 HEP2 transcriptional-unit
    level because the HEPN and zinc-finger rows and rule rows remain unresolved, and
    proposals/metpo_traitmech_v337 reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-29T10:59:37Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-38 system canonical_examples and left them empty because DeWeirdt
    et al. directly support cloned HEP2 assays in E. coli MG1655 and a DefenseFinder
    DS-38 model, but not a direct named native microbial isolate exemplar with experimentally
    verified endogenous DS-38 activity. No paid research was used.
  llm_assisted: true