identifier: traitmech:000430
label: DS-6 system
definition: A phage defense system in which an organism possesses the two-gene DefensePredictor-discovered
  system 6 locus cataloged with working_id HIPA 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-6
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: HipAD
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: HIPA
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: DS-6__DS-6A
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
- synonym_text: DS-6__DS-6B
  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: DOI:10.1126/science.adv7924
  snippet: We independently discovered DS-6 (renamed HipAD) recently
  notes: DeWeirdt et al. record HipAD as a name for DS-6.
- reference: DOI:10.1126/science.adv7924
  snippet: When we mutated a key predicted catalytic residue in DS-6A, we observed
    a loss of defense, suggesting that kinase activity is essential for protection.
  notes: DeWeirdt et al. report that mutating a predicted DS-6A catalytic residue
    eliminated defense.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
  snippet: "HIPA\tNZ_QOWQ01000062.1\tGCF_003334335.1\t-\tTrue\tFalse\tTrue\tTrue\t\
    DefensePredictor hits\t1591\t3164\tDUF3037 domain-containing protein, hypothetical\
    \ protein\tWP_000210934.1, WP_000389051.1\t6.427268761356274\t-2.428836967683248\t\
    True\tFalse\tPredicted novel defense gene\tDS-6"
  notes: The final Science supplementary Table S6 maps working_id HIPA to DS_name
    DS-6, marks the cloned transcriptional unit as defensive, and records NZ_QOWQ01000062.1
    positions 1591-3164 with product accessions WP_000210934.1 and WP_000389051.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tHIPA\t24-03-08\t\
    24-03-08_IMPD_DISA_2CM2_MAZF.png\t3\t5\tY\t5000\t3.9030899869919438\tTrue\tTrue\t\
    \tLB\t37"
  notes: The final Science supplementary Table S7 reports a HIPA assay row with a
    Bas1 phage readout, smaller plaques, and a -log(EOP) value of 3.903.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t3000000\t\
    HIPA\t\t24-07-12\t24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png\t\
    1\t2\t\t20\t5.176091259\nBas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
    3000000\tHIPA\tD139A\t24-07-12\t24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png\t\
    5\t4\t\t400000\t0.8750612634"
  notes: The final Science supplementary Table S7 System Mutants sheet pairs wild-type
    HIPA and HIPA D139A in a Bas1 assay panel, with -log(EOP) shifting from 5.176
    to 0.875 for the D139A catalytic mutant.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\tB.1\tMG1655\t24-07-17_MVB1_VPUS_VAME_EV.png\t3000000\tHIPA\t\t24-07-18\t\
    24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png\t2\t10\t\t\
    1000\t3.477121255\nBas1\tB.1\tMG1655\t24-07-17_MVB1_VPUS_VAME_EV.png\t3000000\t\
    HIPA\tD139A\t24-07-18\t24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png\t\
    6\t4\t\t4000000\t-0.1249387366"
  notes: The final Science supplementary Table S7 System Mutants sheet records a second
    HIPA versus HIPA D139A Bas1 panel, with -log(EOP) shifting from 3.477 to -0.125
    for the D139A catalytic mutant.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "HIPA\tDS-6\tTrue"
  notes: The final Science supplementary Table S8 maps HIPA to replicated display
    name DS-6.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "HIPA\t15.0\t248.0\tWP_000389051.1\tHIPA kinase\tPF20613.3\tHipA_2 ; HipA-like\
    \ kinase\thhpred_9120093.hhr\t15.0\t248.0\t1.0\t2024-07-28 00:00:00"
  notes: The final Science supplementary Table S8 reports a HipA-like kinase HHpred
    hit for WP_000389051.1 in HIPA.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "HIPA\t2.0\t275.0\tWP_000210934.1\tDUF3037\tPF11236.12\tDUF3037\thhpred_4386604.hhr\t\
    7.0\t125.0\t0.9987\t2024-04-15 00:00:00"
  notes: The final Science supplementary Table S8 reports a DUF3037 HHpred hit for
    WP_000210934.1 in HIPA.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "HIPA\t2.0\t275.0\tWP_000210934.1\tDUF1829\tPF08862.14\tDUF1829\thhpred_4386604.hhr\t\
    163.0\t260.0\t0.7785\t2024-04-15 00:00:00"
  notes: The final Science supplementary Table S8 reports a DUF1829 HHpred hit for
    WP_000210934.1 in HIPA.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: '| DS-6 | 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-6 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-6__DS-6A                                      |                                                  |
    DS-6                   | Custom                  | 100    |'
  notes: The pinned DefenseFinder HMM inventory records DS-6__DS-6A as a custom DS-6
    profile.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| DS-6__DS-6B                                      |                                                  |
    DS-6                   | Custom                  | 100    |'
  notes: The pinned DefenseFinder HMM inventory records DS-6__DS-6B as a custom DS-6
    profile.
causal_graphs:
- graph_id: ds_6_locus_reduces_phage_plaquing
  title: DS-6 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the two-gene DS-6 locus to
    reduced bacteriophage plaquing without resolving DS-6 component functions or effector
    activity.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-6 as the validated HIPA transcriptional unit
    with two product accessions and with DefenseFinder DS-6A and DS-6B profile rows.
    It does not assert native host breadth, exact profile-to-protein correspondence,
    the direct viral trigger or substrate, DUF3037 or DUF1829 activity, exact HipA-like
    kinase substrates, phage target breadth, or DefenseFinder rule-level detection
    criteria.
  nodes:
  - node_id: ds_6_locus
    label: DS-6 locus
    node_type: GENETIC_ELEMENT
    description: A two-gene DefensePredictor-discovered system locus represented in
      the pinned DefenseFinder HMM inventory by DS-6A and DS-6B 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 HIPA.
  - node_id: ds_6_system_trait
    label: DS-6 system
    node_type: TRAIT
    grounding: traitmech:000430
    description: Possession of a genome-encoded DS-6 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_6_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-6/HIPA 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: "HIPA\tNZ_QOWQ01000062.1\tGCF_003334335.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t1591\t3164\tDUF3037 domain-containing protein, hypothetical\
        \ protein\tWP_000210934.1, WP_000389051.1\t6.427268761356274\t-2.428836967683248\t\
        True\tFalse\tPredicted novel defense gene\tDS-6"
      notes: The final Science supplementary Table S6 maps working_id HIPA to DS_name
        DS-6, marks the cloned transcriptional unit as defensive, and records NZ_QOWQ01000062.1
        positions 1591-3164 with product accessions WP_000210934.1 and WP_000389051.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tHIPA\t\
        24-03-08\t24-03-08_IMPD_DISA_2CM2_MAZF.png\t3\t5\tY\t5000\t3.9030899869919438\t\
        True\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports a HIPA assay row with
        a Bas1 phage readout, smaller plaques, and a -log(EOP) value of 3.903.
    - reference: DOI:10.1126/science.adv7924
      snippet: When we mutated a key predicted catalytic residue in DS-6A, we observed
        a loss of defense, suggesting that kinase activity is essential for protection.
      notes: DeWeirdt et al. report that DS-6A catalytic residue mutagenesis caused
        loss of defense.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
        3000000\tHIPA\t\t24-07-12\t24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png\t\
        1\t2\t\t20\t5.176091259\nBas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
        3000000\tHIPA\tD139A\t24-07-12\t24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png\t\
        5\t4\t\t400000\t0.8750612634"
      notes: The final Science supplementary Table S7 System Mutants sheet pairs wild-type
        HIPA and HIPA D139A in a Bas1 assay panel, with -log(EOP) shifting from 5.176
        to 0.875 for the D139A catalytic mutant.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\tB.1\tMG1655\t24-07-17_MVB1_VPUS_VAME_EV.png\t3000000\tHIPA\t\
        \t24-07-18\t24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png\t\
        2\t10\t\t1000\t3.477121255\nBas1\tB.1\tMG1655\t24-07-17_MVB1_VPUS_VAME_EV.png\t\
        3000000\tHIPA\tD139A\t24-07-18\t24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png\t\
        6\t4\t\t4000000\t-0.1249387366"
      notes: The final Science supplementary Table S7 System Mutants sheet records
        a second HIPA versus HIPA D139A Bas1 panel, with -log(EOP) shifting from 3.477
        to -0.125 for the D139A catalytic mutant.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_6_system_trait
    description: DS-6-mediated phage plaquing reduction realizes the DS-6 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: "HIPA\tNZ_QOWQ01000062.1\tGCF_003334335.1\t-\tTrue\tFalse\tTrue\tTrue\t\
        DefensePredictor hits\t1591\t3164\tDUF3037 domain-containing protein, hypothetical\
        \ protein\tWP_000210934.1, WP_000389051.1\t6.427268761356274\t-2.428836967683248\t\
        True\tFalse\tPredicted novel defense gene\tDS-6"
      notes: The final Science supplementary Table S6 maps working_id HIPA to DS_name
        DS-6, marks the cloned transcriptional unit as defensive, and records NZ_QOWQ01000062.1
        positions 1591-3164 with product accessions WP_000210934.1 and WP_000389051.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tHIPA\t\
        24-03-08\t24-03-08_IMPD_DISA_2CM2_MAZF.png\t3\t5\tY\t5000\t3.9030899869919438\t\
        True\tTrue\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports a HIPA assay row with
        a Bas1 phage readout, smaller plaques, and a -log(EOP) value of 3.903.
  - subject: ds_6_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-6 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-6 | 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-6 source key to
        the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has
        since been published in Science.
discussions:
- discussion_id: ds-6-defensefinder-model-gap
  prompt: Resolve DS-6 native host breadth, exact two-component activities, DS-6 profile-to-protein
    mapping, sensitive-phage breadth, DUF3037 and DUF1829 activity, HipA-like kinase
    substrates, and rule-level detection criteria before minting narrower DS-6 mechanism
    children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-6 as the defensive HIPA transcriptional unit
    that reduced Bas1 plaquing when cloned in E. coli MG1655, and the pinned DefenseFinder
    HMM inventory records two DS-6 profile rows. The pinned rules table has no DS-6
    row, and the first-pass record does not resolve native host breadth, exact profile-to-protein
    correspondence, DUF3037 or HipA-like kinase activity, phage target breadth, or
    endogenous DS-6 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: DOI:10.1126/science.adv7924
    snippet: We independently discovered DS-6 (renamed HipAD) recently
    notes: DeWeirdt et al. record HipAD as a DS-6 name.
  - reference: DOI:10.1126/science.adv7924
    snippet: When we mutated a key predicted catalytic residue in DS-6A, we observed
      a loss of defense, suggesting that kinase activity is essential for protection.
    notes: DeWeirdt et al. report loss of defense after mutation of a predicted DS-6A
      catalytic residue.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
    snippet: "HIPA\tNZ_QOWQ01000062.1\tGCF_003334335.1\t-\tTrue\tFalse\tTrue\tTrue\t\
      DefensePredictor hits\t1591\t3164\tDUF3037 domain-containing protein, hypothetical\
      \ protein\tWP_000210934.1, WP_000389051.1\t6.427268761356274\t-2.428836967683248\t\
      True\tFalse\tPredicted novel defense gene\tDS-6"
    notes: The final Science supplementary Table S6 maps working_id HIPA to DS_name
      DS-6, marks the cloned transcriptional unit as defensive, and records NZ_QOWQ01000062.1
      positions 1591-3164 with product accessions WP_000210934.1 and WP_000389051.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tHIPA\t24-03-08\t\
      24-03-08_IMPD_DISA_2CM2_MAZF.png\t3\t5\tY\t5000\t3.9030899869919438\tTrue\t\
      True\t\tLB\t37"
    notes: The final Science supplementary Table S7 reports a HIPA assay row with
      a Bas1 phage readout, smaller plaques, and a -log(EOP) value of 3.903.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      3000000\tHIPA\t\t24-07-12\t24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png\t\
      1\t2\t\t20\t5.176091259\nBas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      3000000\tHIPA\tD139A\t24-07-12\t24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png\t\
      5\t4\t\t400000\t0.8750612634"
    notes: The final Science supplementary Table S7 System Mutants sheet pairs wild-type
      HIPA and HIPA D139A in a Bas1 assay panel, with -log(EOP) shifting from 5.176
      to 0.875 for the D139A catalytic mutant.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\tB.1\tMG1655\t24-07-17_MVB1_VPUS_VAME_EV.png\t3000000\tHIPA\t\t\
      24-07-18\t24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png\t\
      2\t10\t\t1000\t3.477121255\nBas1\tB.1\tMG1655\t24-07-17_MVB1_VPUS_VAME_EV.png\t\
      3000000\tHIPA\tD139A\t24-07-18\t24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png\t\
      6\t4\t\t4000000\t-0.1249387366"
    notes: The final Science supplementary Table S7 System Mutants sheet records a
      second HIPA versus HIPA D139A Bas1 panel, with -log(EOP) shifting from 3.477
      to -0.125 for the D139A catalytic mutant.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "HIPA\tDS-6\tTrue"
    notes: The final Science supplementary Table S8 maps HIPA to replicated display
      name DS-6.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "HIPA\t15.0\t248.0\tWP_000389051.1\tHIPA kinase\tPF20613.3\tHipA_2 ;\
      \ HipA-like kinase\thhpred_9120093.hhr\t15.0\t248.0\t1.0\t2024-07-28 00:00:00"
    notes: The final Science supplementary Table S8 reports a HipA-like kinase HHpred
      hit for WP_000389051.1 in HIPA.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "HIPA\t2.0\t275.0\tWP_000210934.1\tDUF3037\tPF11236.12\tDUF3037\thhpred_4386604.hhr\t\
      7.0\t125.0\t0.9987\t2024-04-15 00:00:00"
    notes: The final Science supplementary Table S8 reports a DUF3037 HHpred hit for
      WP_000210934.1 in HIPA.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "HIPA\t2.0\t275.0\tWP_000210934.1\tDUF1829\tPF08862.14\tDUF1829\thhpred_4386604.hhr\t\
      163.0\t260.0\t0.7785\t2024-04-15 00:00:00"
    notes: The final Science supplementary Table S8 reports a DUF1829 HHpred hit for
      WP_000210934.1 in HIPA.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    snippet: '| DS-6 | 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-6 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-6__DS-6A                                      |                                                  |
      DS-6                   | Custom                  | 100    |'
    notes: The pinned DefenseFinder HMM inventory records DS-6__DS-6A as a custom
      DS-6 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
    snippet: '| DS-6__DS-6B                                      |                                                  |
      DS-6                   | Custom                  | 100    |'
    notes: The pinned DefenseFinder HMM inventory records DS-6__DS-6B as a custom
      DS-6 profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table does not list DS-6, leaving rule-level
      detection criteria unresolved.
  attaches_to:
  - causal_graphs#ds_6_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-28'
curation_history:
- timestamp: '2026-09-28T09:20:00Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-6 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 HIPA transcriptional-unit
    level because the pinned DefenseFinder DS-6 HMM rows are not backed by a rules
    row; proposals/metpo_traitmech_v307 reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-28T09:20:01Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-6 system canonical_examples and left them empty because DeWeirdt
    et al. support cloned HIPA plaquing assays in E. coli MG1655 plus a DefenseFinder
    DS-6 model, but not a direct named native microbial isolate exemplar with experimentally
    verified endogenous DS-6 activity. No paid research was used.
  llm_assisted: true