DS-4 system

traitmech:000427 · CLASS · PROPOSED

A phage defense system in which an organism possesses the five-gene DefensePredictor-discovered system 4 locus cataloged as working transcriptional unit NTTI and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing.

Trait evidence (11)

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
NTTI NZ_QOYB01000018.1 GCF_003333785.1 + True False True True DefensePredictor hits 32107 36002 thymidylate synthase, adenylate kinase, putative DNA base hypermodification protein, TIR domain-containing protein, hypothetical protein WP_087900468.1, WP_087900469.1, WP_087900470.1, WP_072044445.1, WP_047174762.1 8.47705415994386 4.820281565605036 True True Predicted novel defense gene DS-4

The final Science supplementary Table S6 maps working_id NTTI to DS_name DS-4, marks the cloned transcriptional unit as defensive, and records NZ_QOYB01000018.1 positions 32107-36002 with product accessions WP_087900468.1, WP_087900469.1, WP_087900470.1, WP_072044445.1, and WP_047174762.1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Lambda 1.1 pLAND 24-03-08_NYND_PIN2_MHAD_EV.png 60000000 NTTI 24-03-12 24-03-12_NTTI_PN12_SVIR_D390.png 6 7 Y 7000000 0.9330532103693868 True True LB 37

The final Science supplementary Table S7 reports an NTTI assay row with a lambda phage readout, smaller plaque size marked Y, and a -log(EOP) value of 0.933.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
NTTI DS-4 True

The final Science supplementary Table S8 maps NTTI to replicated display name DS-4.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-4 | 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-4 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-4__DS-4A | | DS-4 | Custom | 150 |

The pinned DefenseFinder HMM inventory records DS-4__DS-4A as a custom DS-4 profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4B | | DS-4 | Custom | 200 |

The pinned DefenseFinder HMM inventory records DS-4__DS-4B as a custom DS-4 profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4C | | DS-4 | Custom | 150 |

The pinned DefenseFinder HMM inventory records DS-4__DS-4C as a custom DS-4 profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4D | | DS-4 | Custom | 100 |

The pinned DefenseFinder HMM inventory records DS-4__DS-4D as a custom DS-4 profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4E | | DS-4 | Custom | 50 |

The pinned DefenseFinder HMM inventory records DS-4__DS-4E as a custom DS-4 profile.

DS-4 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the five-gene DS-4 locus to reduced bacteriophage plaquing without resolving DS-4 component functions or effector activity.

NONMECHANISTIC · The graph captures DS-4 as the validated NTTI transcriptional unit with five product accessions and with DefenseFinder DS-4A, DS-4B, DS-4C, DS-4D, and DS-4E profile rows. It does not assert native host breadth, exact profile-to-protein correspondence, the direct viral trigger or substrate, exact molecular output, phage target breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-4 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-4/NTTI locus contributes to reduced bacteriophage plaquing when plasmid expressed.
- 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 validate DefensePredictor-discovered systems by assaying cloned transcriptional units against E. coli phages.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx NTTI NZ_QOYB01000018.1 GCF_003333785.1 + True False True True DefensePredictor hits 32107 36002 thymidylate synthase, adenylate kinase, putative DNA base hypermodification protein, TIR domain-containing protein, hypothetical protein WP_087900468.1, WP_087900469.1, WP_087900470.1, WP_072044445.1, WP_047174762.1 8.47705415994386 4.820281565605036 True True Predicted novel defense gene DS-4 The final Science supplementary Table S6 maps working_id NTTI to DS_name DS-4, marks the cloned transcriptional unit as defensive, and records NZ_QOYB01000018.1 positions 32107-36002 with product accessions WP_087900468.1, WP_087900469.1, WP_087900470.1, WP_072044445.1, and WP_047174762.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Lambda 1.1 pLAND 24-03-08_NYND_PIN2_MHAD_EV.png 60000000 NTTI 24-03-12 24-03-12_NTTI_PN12_SVIR_D390.png 6 7 Y 7000000 0.9330532103693868 True True LB 37 The final Science supplementary Table S7 reports an NTTI assay row with a lambda phage readout, smaller plaque size marked Y, and a -log(EOP) value of 0.933.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-4__DS-4A | | DS-4 | Custom | 150 | The pinned DefenseFinder HMM inventory records DS-4__DS-4A as a custom DS-4 profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-4__DS-4B | | DS-4 | Custom | 200 | The pinned DefenseFinder HMM inventory records DS-4__DS-4B as a custom DS-4 profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-4__DS-4C | | DS-4 | Custom | 150 | The pinned DefenseFinder HMM inventory records DS-4__DS-4C as a custom DS-4 profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-4__DS-4D | | DS-4 | Custom | 100 | The pinned DefenseFinder HMM inventory records DS-4__DS-4D as a custom DS-4 profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-4__DS-4E | | DS-4 | Custom | 50 | The pinned DefenseFinder HMM inventory records DS-4__DS-4E as a custom DS-4 profile.
reduced bacteriophage plaquing confers DS-4 system METPO:2007700
DS-4-mediated phage plaquing reduction realizes the DS-4 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 each validated transcriptional unit as a DefensePredictor discovered system.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx NTTI NZ_QOYB01000018.1 GCF_003333785.1 + True False True True DefensePredictor hits 32107 36002 thymidylate synthase, adenylate kinase, putative DNA base hypermodification protein, TIR domain-containing protein, hypothetical protein WP_087900468.1, WP_087900469.1, WP_087900470.1, WP_072044445.1, WP_047174762.1 8.47705415994386 4.820281565605036 True True Predicted novel defense gene DS-4 The final Science supplementary Table S6 maps working_id NTTI to DS_name DS-4, marks the cloned transcriptional unit as defensive, and records NZ_QOYB01000018.1 positions 32107-36002 with product accessions WP_087900468.1, WP_087900469.1, WP_087900470.1, WP_072044445.1, and WP_047174762.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Lambda 1.1 pLAND 24-03-08_NYND_PIN2_MHAD_EV.png 60000000 NTTI 24-03-12 24-03-12_NTTI_PN12_SVIR_D390.png 6 7 Y 7000000 0.9330532103693868 True True LB 37 The final Science supplementary Table S7 reports an NTTI assay row with a lambda phage readout, smaller plaque size marked Y, and a -log(EOP) value of 0.933.
DS-4 system is a phage defense system rdfs:subClassOf
DS-4 system possession is a phage-defense-system trait.
- 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. validate DSs as anti-phage systems.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md | DS-4 | 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-4 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 (7)

DS-4 EXACT_SYNONYM · DOI:10.1126/science.adv7924
NTTI RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-4__DS-4A RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-4__DS-4B RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-4__DS-4C RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-4__DS-4D RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-4__DS-4E 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-4 native host breadth, exact five-component activities, DS-4 profile-to-protein mapping, sensitive-phage breadth, molecular output, and rule-level detection criteria before minting narrower DS-4 mechanism children.

KNOWLEDGE GAP OPEN ds-4-defensefinder-model-gap · raised by codex · 2026-09-28

Attached to causal_graphs#ds_4_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-4 as the defensive NTTI transcriptional unit that reduced plaquing when cloned in E. coli MG1655, and the pinned DefenseFinder HMM inventory records five DS-4 profile rows. The pinned rules table has no DS-4 row, and the first-pass record does not resolve native host breadth, exact component activities, profile-to-protein mapping, phage target breadth, or endogenous DS-4 activity.

Evidence

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
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
NTTI NZ_QOYB01000018.1 GCF_003333785.1 + True False True True DefensePredictor hits 32107 36002 thymidylate synthase, adenylate kinase, putative DNA base hypermodification protein, TIR domain-containing protein, hypothetical protein WP_087900468.1, WP_087900469.1, WP_087900470.1, WP_072044445.1, WP_047174762.1 8.47705415994386 4.820281565605036 True True Predicted novel defense gene DS-4
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Lambda 1.1 pLAND 24-03-08_NYND_PIN2_MHAD_EV.png 60000000 NTTI 24-03-12 24-03-12_NTTI_PN12_SVIR_D390.png 6 7 Y 7000000 0.9330532103693868 True True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
NTTI DS-4 True
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-4 | 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-4__DS-4A | | DS-4 | Custom | 150 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4B | | DS-4 | Custom | 200 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4C | | DS-4 | Custom | 150 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4D | | DS-4 | Custom | 100 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-4__DS-4E | | DS-4 | Custom | 50 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-28T06:12:08Z · MINTED_TRAITMECH_ID · codex
Minted DS-4 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 NTTI transcriptional-unit level because the pinned DefenseFinder DS-4 HMM rows are not backed by a rules row; proposals/metpo_traitmech_v304 reserves the replacement placeholder.
2026-09-28T06:12:09Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-4 system canonical_examples and left them empty because DeWeirdt et al. support cloned NTTI plaquing assays in E. coli MG1655 plus a DefenseFinder DS-4 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-4 activity. No paid research was used.