DS-21 system

traitmech:000446 · CLASS · PROPOSED

A phage defense system in which an organism possesses the three-gene DefensePredictor-discovered system 21 locus cataloged as working transcriptional unit TOXO and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing.

Trait evidence (8)

DOI:10.1126/science.adv7924
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

DeWeirdt et al. experimentally validated 42 predicted transcriptional units as phage-defense systems in E. coli.
DOI:10.1126/science.adv7924
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.

DeWeirdt et al. name validated transcriptional units as DefensePredictor discovered systems.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
TOXO NZ_QOXJ01000032.1 GCF_003334085.1 - True False False True DefensePredictor hits 7805 9963 hypothetical protein, hypothetical protein, hypothetical protein WP_001532221.1, WP_001557682.1, WP_021552536.1 10.9763556055726 2.883007179633958 True True Predicted novel defense gene DS-21

The final Science supplementary Table S6 maps working_id TOXO to DS_name DS-21, marks the cloned transcriptional unit as defensive, and records NZ_QOXJ01000032.1 positions 7805-9963 with three product accessions.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 6.1 pLAND 24-07-17_MVB1_VPUS_VAME_EV.png 3000000 TOXO 24-07-25 24-07-25_PDX1_TMO1_VANC_TOXO.png 2 1 100 4.477121254719663 True LB 37

The final Science supplementary Table S7 reports a TOXO assay row with a Bas1 phage readout and a -log(EOP) value of 4.477.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
TOXO DS-21 True

The final Science supplementary Table S8 maps TOXO to replicated display name DS-21.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
TOXO 3.0 211.0 WP_001557682.1 PDDEXK PF18742.6 DpnII-MboI ; REase_DpnII-MboI hhpred_4621019.hhr 37.0 160.0 0.96 2024-07-29 00:00:00 121-123 103.0

The final Science supplementary Table S8 reports a PDDEXK HHpred hit for WP_001557682.1 in TOXO.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-21 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems |

The pinned DefenseFinder article registry maps the DS-21 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-21__DS-21A | | DS-21 | Custom | 20 | | DS-21__DS-21B | | DS-21 | Custom | 250 | | DS-21__DS-21C | | DS-21 | Custom | 70 |

The pinned DefenseFinder HMM inventory records three DS-21 custom profiles: DS-21__DS-21A, DS-21__DS-21B, and DS-21__DS-21C.

DS-21 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the three-gene DS-21 locus to reduced bacteriophage plaquing without resolving DS-21 component function or molecular output.

NONMECHANISTIC · The graph captures DS-21 as the validated TOXO transcriptional unit with three product accessions, a PDDEXK HHpred-domain row, and three DefenseFinder DS-21 profile rows. It does not assert native host breadth, exact profile-to-protein correspondence, DS-21 molecular activity, trigger, substrate, complete phage breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-21 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-21/TOXO locus contributes to reduced bacteriophage plaquing in heterologous E. coli MG1655 plasmid-expression assays.
- DOI:10.1126/science.adv7924 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 DeWeirdt et al. describe the plasmid-based phage challenge used to validate predicted transcriptional units.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx TOXO NZ_QOXJ01000032.1 GCF_003334085.1 - True False False True DefensePredictor hits 7805 9963 hypothetical protein, hypothetical protein, hypothetical protein WP_001532221.1, WP_001557682.1, WP_021552536.1 10.9763556055726 2.883007179633958 True True Predicted novel defense gene DS-21 The final Science supplementary Table S6 maps working_id TOXO to DS_name DS-21, marks the cloned transcriptional unit as defensive, and records NZ_QOXJ01000032.1 positions 7805-9963 with three product accessions.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 6.1 pLAND 24-07-17_MVB1_VPUS_VAME_EV.png 3000000 TOXO 24-07-25 24-07-25_PDX1_TMO1_VANC_TOXO.png 2 1 100 4.477121254719663 True LB 37 The final Science supplementary Table S7 reports a TOXO assay row with a Bas1 phage readout and a -log(EOP) value of 4.477.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx TOXO DS-21 True The final Science supplementary Table S8 maps TOXO to replicated display name DS-21.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-21__DS-21A | | DS-21 | Custom | 20 | | DS-21__DS-21B | | DS-21 | Custom | 250 | | DS-21__DS-21C | | DS-21 | Custom | 70 | The pinned DefenseFinder HMM inventory records three DS-21 custom profiles: DS-21__DS-21A, DS-21__DS-21B, and DS-21__DS-21C.
reduced bacteriophage plaquing confers DS-21 system METPO:2007700
DS-21-mediated phage plaquing reduction realizes the DS-21 system trait.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx TOXO NZ_QOXJ01000032.1 GCF_003334085.1 - True False False True DefensePredictor hits 7805 9963 hypothetical protein, hypothetical protein, hypothetical protein WP_001532221.1, WP_001557682.1, WP_021552536.1 10.9763556055726 2.883007179633958 True True Predicted novel defense gene DS-21 The final Science supplementary Table S6 maps working_id TOXO to DS_name DS-21, marks the cloned transcriptional unit as defensive, and records NZ_QOXJ01000032.1 positions 7805-9963 with three product accessions.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 6.1 pLAND 24-07-17_MVB1_VPUS_VAME_EV.png 3000000 TOXO 24-07-25 24-07-25_PDX1_TMO1_VANC_TOXO.png 2 1 100 4.477121254719663 True LB 37 The final Science supplementary Table S7 reports a TOXO assay row with a Bas1 phage readout and a -log(EOP) value of 4.477.
- DOI:10.1126/science.adv7924 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. The DS nomenclature is used for DefensePredictor discovered systems.
DS-21 system is a phage defense system rdfs:subClassOf
DS-21 system possession is a phage-defense-system trait.
- DOI:10.1126/science.adv7924 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. DeWeirdt et al. name validated TUs as DefensePredictor discovered systems.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md | DS-21 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | The pinned DefenseFinder article registry maps the DS-21 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science.

Provenance

Identifier source: TraitMech local identifier
Definition source: DOI:10.1126/science.adv7924

Parent traits (1)

phage defense system traitmech:000209

Synonyms (5)

DS-21 EXACT_SYNONYM · DOI:10.1126/science.adv7924
TOXO RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-21__DS-21A RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-21__DS-21B RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-21__DS-21C RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md

kg-microbe context

No kg-microbe node embedding matched this record in the 2026-04-25 deepwalk.

Discussions and Knowledge Gaps (1)

Open questions attached to this trait. Seeded by just knowledge-gap-scan and curated; see the corpus-wide index.

Resolve DS-21 native host breadth, exact profile-to-protein mapping, HHpred-domain interpretation, component chemistry, complete phage breadth, molecular output, and rule-level DefenseFinder criteria before minting narrower DS-21 mechanism children.

KNOWLEDGE GAP OPEN ds-21-defensefinder-model-gap · raised by codex · 2026-09-28

Attached to causal_graphs#ds_21_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-21 as the defensive TOXO transcriptional unit and final Science Tables S6/S7/S8 map it to three product accessions, a Bas1 phage readout, display name DS-21, and a PDDEXK HHpred row. The pinned DefenseFinder HMM inventory records three DS-21 custom profile rows. The pinned rules table has no DS-21 row, and the first-pass record does not resolve native host breadth, complete phage breadth, direct profile-to-protein correspondence, PDDEXK nuclease activity, molecular output, or endogenous DS-21 activity.

Evidence

DOI:10.1126/science.adv7924
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.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
TOXO NZ_QOXJ01000032.1 GCF_003334085.1 - True False False True DefensePredictor hits 7805 9963 hypothetical protein, hypothetical protein, hypothetical protein WP_001532221.1, WP_001557682.1, WP_021552536.1 10.9763556055726 2.883007179633958 True True Predicted novel defense gene DS-21
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 6.1 pLAND 24-07-17_MVB1_VPUS_VAME_EV.png 3000000 TOXO 24-07-25 24-07-25_PDX1_TMO1_VANC_TOXO.png 2 1 100 4.477121254719663 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
TOXO DS-21 True
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
TOXO 3.0 211.0 WP_001557682.1 PDDEXK PF18742.6 DpnII-MboI ; REase_DpnII-MboI hhpred_4621019.hhr 37.0 160.0 0.96 2024-07-29 00:00:00 121-123 103.0
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-21 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-21__DS-21A | | DS-21 | Custom | 20 | | DS-21__DS-21B | | DS-21 | Custom | 250 | | DS-21__DS-21C | | DS-21 | Custom | 70 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-28T22:17:01Z · MINTED_TRAITMECH_ID · codex
Minted DS-21 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 TOXO transcriptional-unit level because PDDEXK chemistry and rule rows remain unresolved, and proposals/metpo_traitmech_v323 reserves the replacement placeholder.
2026-09-28T22:17:02Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-21 system canonical_examples and left them empty because DeWeirdt et al. directly support cloned TOXO assays in E. coli MG1655 and DefenseFinder DS-21 models, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-21 activity. No paid research was used.