identifier: traitmech:000472
label: DS-26 system
definition: A phage defense system in which an organism possesses the single-gene
  DefensePredictor-discovered system 26 locus cataloged as working transcriptional
  unit NERD 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-26
  synonym_type: EXACT_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: NERD
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
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: "NERD\tNZ_QOXL01000006.1\tGCF_003334035.1\t-\tTrue\tFalse\tFalse\tTrue\t\
    DefensePredictor hits\t203139\t204737\thypothetical protein\tWP_054626965.1\t\
    9.096479385650875\t4.498799058824351\tTrue\tTrue\tRemote defense homolog\tDS-26"
  notes: The final Science supplementary Table S6 maps working_id NERD to DS_name
    DS-26, marks the cloned transcriptional unit as defensive, and records NZ_QOXL01000006.1
    positions 203139-204737 with product accession WP_054626965.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas25\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t50000000\tNERD\t24-07-17\t\
    24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t3\t\t30\t6.221848749616356\t\t\tTrue\tLB\t\
    37"
  notes: The final Science supplementary Table S7 Systems sheet reports a NERD assay
    row with a Bas25 phage readout and a -log(EOP) value of 6.222.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas19\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t2200000\tNERD\t24-07-17\t\
    24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t2\t\t20\t5.041392685158225\t\t\tTrue\tLB\t\
    37"
  notes: The final Science supplementary Table S7 Systems sheet reports a NERD assay
    row with a Bas19 phage readout and a -log(EOP) value of 5.041.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "NERD\tDS-26\tTrue"
  notes: The final Science supplementary Table S8 maps NERD to replicated display
    name DS-26.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "NERD\t1.0\t532.0\tWP_054626965.1\tPDDEXK\tPF09254.16\tFokI_cleav_dom ;\
    \ FokI, cleavage domain\thhpred_1843394.hhr\t282.0\t459.0\t0.95\t2024-07-29 00:00:00\t\
    77-79\t63.0"
  notes: The final Science supplementary Table S8 reports a PDDEXK/FokI cleavage-domain
    HHpred lead for WP_054626965.1 in NERD; this first-pass record records it as source
    context without resolving DS-26 molecular activity.
causal_graphs:
- graph_id: ds_26_locus_reduces_phage_plaquing
  title: DS-26 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the single-gene DS-26 locus
    to reduced bacteriophage plaquing without resolving DS-26 nuclease chemistry,
    native activity, DefenseFinder model coverage, or molecular output.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-26 as the validated NERD transcriptional unit
    with one product accession, two Table S7 phage-specific readouts, and one Table
    S8 PDDEXK/FokI cleavage-domain HHpred lead for WP_054626965.1. It does not assert
    exact domain interpretation, nuclease chemistry, native host breadth, complete
    phage breadth, DefenseFinder article/HMM/rules coverage, molecular output, or
    endogenous DS-26 activity.
  nodes:
  - node_id: ds_26_locus
    label: DS-26 locus
    node_type: GENETIC_ELEMENT
    description: A single-gene DS-26 locus cataloged as working transcriptional unit
      NERD in final Science supplementary Table S6.
  - node_id: reduced_phage_plaquing
    label: reduced bacteriophage plaquing
    node_type: BIOLOGICAL_PROCESS
    description: Reduced bacteriophage plaquing in cells carrying cloned NERD.
  - node_id: ds_26_system_trait
    label: DS-26 system
    node_type: TRAIT
    grounding: traitmech:000472
    description: Possession of a genome-encoded DS-26 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_26_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-26/NERD 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: "NERD\tNZ_QOXL01000006.1\tGCF_003334035.1\t-\tTrue\tFalse\tFalse\t\
        True\tDefensePredictor hits\t203139\t204737\thypothetical protein\tWP_054626965.1\t\
        9.096479385650875\t4.498799058824351\tTrue\tTrue\tRemote defense homolog\t\
        DS-26"
      notes: The final Science supplementary Table S6 maps working_id NERD to DS_name
        DS-26, marks the cloned transcriptional unit as defensive, and records NZ_QOXL01000006.1
        positions 203139-204737 with product accession WP_054626965.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas25\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t50000000\tNERD\t\
        24-07-17\t24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t3\t\t30\t6.221848749616356\t\
        \t\tTrue\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports a NERD
        assay row with a Bas25 phage readout and a -log(EOP) value of 6.222.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas19\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t2200000\tNERD\t\
        24-07-17\t24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t2\t\t20\t5.041392685158225\t\
        \t\tTrue\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports a NERD
        assay row with a Bas19 phage readout and a -log(EOP) value of 5.041.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "NERD\tDS-26\tTrue"
      notes: The final Science supplementary Table S8 maps NERD to replicated display
        name DS-26.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
      snippet: "NERD\t1.0\t532.0\tWP_054626965.1\tPDDEXK\tPF09254.16\tFokI_cleav_dom\
        \ ; FokI, cleavage domain\thhpred_1843394.hhr\t282.0\t459.0\t0.95\t2024-07-29\
        \ 00:00:00\t77-79\t63.0"
      notes: The final Science supplementary Table S8 reports a PDDEXK/FokI cleavage-domain
        HHpred lead for WP_054626965.1 in NERD; this first-pass record records it
        as source context without resolving DS-26 molecular activity.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_26_system_trait
    description: DS-26-mediated phage plaquing reduction realizes the DS-26 system
      trait.
    evidence:
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "NERD\tNZ_QOXL01000006.1\tGCF_003334035.1\t-\tTrue\tFalse\tFalse\t\
        True\tDefensePredictor hits\t203139\t204737\thypothetical protein\tWP_054626965.1\t\
        9.096479385650875\t4.498799058824351\tTrue\tTrue\tRemote defense homolog\t\
        DS-26"
      notes: The final Science supplementary Table S6 maps working_id NERD to DS_name
        DS-26, marks the cloned transcriptional unit as defensive, and records NZ_QOXL01000006.1
        positions 203139-204737 with product accession WP_054626965.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas25\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t50000000\tNERD\t\
        24-07-17\t24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t3\t\t30\t6.221848749616356\t\
        \t\tTrue\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports a NERD
        assay row with a Bas25 phage readout and a -log(EOP) value of 6.222.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas19\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t2200000\tNERD\t\
        24-07-17\t24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t2\t\t20\t5.041392685158225\t\
        \t\tTrue\tLB\t37"
      notes: The final Science supplementary Table S7 Systems sheet reports a NERD
        assay row with a Bas19 phage readout and a -log(EOP) value of 5.041.
    - 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_26_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-26 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 DSs.
discussions:
- discussion_id: ds-26-defensefinder-model-gap
  prompt: Resolve DS-26 native host breadth, exact component activity, PDDEXK/FokI
    HHpred-domain interpretation, nuclease chemistry, complete phage breadth, molecular
    output, and DefenseFinder model coverage before minting narrower DS-26 mechanism
    children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-26 as the defensive NERD transcriptional unit
    and final Science Tables S6/S7/S8 map it to one product accession, Bas25 and Bas19
    phage readouts, display name DS-26, and a PDDEXK/FokI cleavage-domain HHpred row.
    A first-pass pinned DefenseFinder review found no exact DS-26 article, HMM, or
    rules row, and the first-pass record therefore does not resolve native host breadth,
    complete phage breadth, domain interpretation, nuclease chemistry, molecular output,
    or endogenous DS-26 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: "NERD\tNZ_QOXL01000006.1\tGCF_003334035.1\t-\tTrue\tFalse\tFalse\tTrue\t\
      DefensePredictor hits\t203139\t204737\thypothetical protein\tWP_054626965.1\t\
      9.096479385650875\t4.498799058824351\tTrue\tTrue\tRemote defense homolog\tDS-26"
    notes: The final Science supplementary Table S6 maps working_id NERD to DS_name
      DS-26, marks the cloned transcriptional unit as defensive, and records NZ_QOXL01000006.1
      positions 203139-204737 with product accession WP_054626965.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas25\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t50000000\tNERD\t\
      24-07-17\t24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t3\t\t30\t6.221848749616356\t\t\
      \tTrue\tLB\t37"
    notes: The final Science supplementary Table S7 Systems sheet reports a NERD assay
      row with a Bas25 phage readout and a -log(EOP) value of 6.222.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas19\t6.1\tpLAND\t24-07-17_MVB1_VPUS_VAME_EV.png\t2200000\tNERD\t24-07-17\t\
      24-07-17_AAA2_RMOR_NERD_NUCS.png\t1\t2\t\t20\t5.041392685158225\t\t\tTrue\t\
      LB\t37"
    notes: The final Science supplementary Table S7 Systems sheet reports a NERD assay
      row with a Bas19 phage readout and a -log(EOP) value of 5.041.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "NERD\tDS-26\tTrue"
    notes: The final Science supplementary Table S8 maps NERD to replicated display
      name DS-26.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "NERD\t1.0\t532.0\tWP_054626965.1\tPDDEXK\tPF09254.16\tFokI_cleav_dom\
      \ ; FokI, cleavage domain\thhpred_1843394.hhr\t282.0\t459.0\t0.95\t2024-07-29\
      \ 00:00:00\t77-79\t63.0"
    notes: The final Science supplementary Table S8 reports a PDDEXK/FokI cleavage-domain
      HHpred lead for WP_054626965.1 in NERD; this first-pass record records it as
      source context without resolving DS-26 molecular activity.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    notes: The pinned DefenseFinder article registry has no exact DS-26 or source-key
      NERD row.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
    notes: The pinned DefenseFinder HMM inventory has no exact DS-26 or DS-26__DS-26
      profile row; the NERD substring occurs only in an unrelated UG34__NERD_Helicase
      profile row.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table has no exact DS-26 or source-key NERD
      model row.
  attaches_to:
  - causal_graphs#ds_26_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-29'
curation_history:
- timestamp: '2026-09-29T19:30:01Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-26 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 NERD transcriptional-unit
    level because native host breadth, exact component activity, complete phage breadth,
    DefenseFinder model coverage, nuclease chemistry, and molecular output remain
    unresolved, and proposals/metpo_traitmech_v349 reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-29T19:30:02Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-26 system canonical_examples and left them empty because DeWeirdt
    et al. directly support cloned NERD assays in E. coli MG1655, but not a direct
    named native microbial isolate exemplar with experimentally verified endogenous
    DS-26 activity. No paid research was used.
  llm_assisted: true