DS-40 system

traitmech:000462 · CLASS · PROPOSED

A phage defense system in which an organism possesses the single-gene DefensePredictor-discovered system 40 locus cataloged as working transcriptional unit D295 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
D295 NZ_QOYF01000088.1 GCF_003334585.1 + True False True True DefensePredictor hits 10328 11263 hypothetical protein WP_097419291.1 4.659671153870749 1.141745659485685 True True Predicted novel defense gene DS-40

The final Science supplementary Table S6 maps working_id D295 to DS_name DS-40, marks the cloned transcriptional unit as defensive, and records NZ_QOYF01000088.1 positions 10328-11263 with product accession WP_097419291.1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas26 2.2 pLAND 24-03-12_EV.png 2400000000 D295 24-03-14 24-03-14_RED5_D295_6236_D932.png 3 100 Y 100000 4.380211241711606 True LB 37

The final Science supplementary Table S7 Systems sheet reports a D295 assay row with a Bas26 phage readout and a -log(EOP) value of 4.380.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
D295 DS-40 True

The final Science supplementary Table S8 maps D295 to replicated display name DS-40.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
D295 1.0 311.0 WP_097419291.1 DUF6680 PF20385.2 DUF6680 ; Family of unknown function (DUF6680) hhpred_5944942.hhr 27.0 238.0 0.7883 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a moderate-probability DUF6680 HHpred hit for WP_097419291.1 in D295.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-40 | 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-40 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-40__DS-40 | | DS-40 | Custom | 180 |

The pinned DefenseFinder HMM inventory records DS-40__DS-40 as a custom DS-40 profile.

DS-40 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the single-gene DS-40 locus to reduced bacteriophage plaquing without resolving DS-40 component function or molecular output.

NONMECHANISTIC · The graph captures DS-40 as the validated D295 transcriptional unit with one product accession, one moderate-probability DUF6680 HHpred row for WP_097419291.1, and one DefenseFinder DS-40 profile row. It does not assert exact profile-to-protein correspondence, DUF6680 activity, native host breadth, DS-40 molecular output, complete phage breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-40 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-40/D295 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 D295 NZ_QOYF01000088.1 GCF_003334585.1 + True False True True DefensePredictor hits 10328 11263 hypothetical protein WP_097419291.1 4.659671153870749 1.141745659485685 True True Predicted novel defense gene DS-40 The final Science supplementary Table S6 maps working_id D295 to DS_name DS-40, marks the cloned transcriptional unit as defensive, and records NZ_QOYF01000088.1 positions 10328-11263 with product accession WP_097419291.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas26 2.2 pLAND 24-03-12_EV.png 2400000000 D295 24-03-14 24-03-14_RED5_D295_6236_D932.png 3 100 Y 100000 4.380211241711606 True LB 37 The final Science supplementary Table S7 Systems sheet reports a D295 assay row with a Bas26 phage readout and a -log(EOP) value of 4.380.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx D295 DS-40 True The final Science supplementary Table S8 maps D295 to replicated display name DS-40.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx D295 1.0 311.0 WP_097419291.1 DUF6680 PF20385.2 DUF6680 ; Family of unknown function (DUF6680) hhpred_5944942.hhr 27.0 238.0 0.7883 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a moderate-probability DUF6680 HHpred hit for WP_097419291.1 in D295.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-40__DS-40 | | DS-40 | Custom | 180 | The pinned DefenseFinder HMM inventory records DS-40__DS-40 as a custom DS-40 profile.
reduced bacteriophage plaquing confers DS-40 system METPO:2007700
DS-40-mediated phage plaquing reduction realizes the DS-40 system trait.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx D295 NZ_QOYF01000088.1 GCF_003334585.1 + True False True True DefensePredictor hits 10328 11263 hypothetical protein WP_097419291.1 4.659671153870749 1.141745659485685 True True Predicted novel defense gene DS-40 The final Science supplementary Table S6 maps working_id D295 to DS_name DS-40, marks the cloned transcriptional unit as defensive, and records NZ_QOYF01000088.1 positions 10328-11263 with product accession WP_097419291.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas26 2.2 pLAND 24-03-12_EV.png 2400000000 D295 24-03-14 24-03-14_RED5_D295_6236_D932.png 3 100 Y 100000 4.380211241711606 True LB 37 The final Science supplementary Table S7 Systems sheet reports a D295 assay row with a Bas26 phage readout and a -log(EOP) value of 4.380.
- 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-40 system is a phage defense system rdfs:subClassOf
DS-40 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-40 | 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-40 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 (3)

DS-40 EXACT_SYNONYM · DOI:10.1126/science.adv7924
D295 RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-40__DS-40 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-40 native host breadth, exact component activity, profile-to-protein mapping, DUF6680 interpretation, complete phage breadth, molecular output, and rule-level DefenseFinder criteria before minting narrower DS-40 mechanism children.

KNOWLEDGE GAP OPEN ds-40-defensefinder-model-gap · raised by codex · 2026-09-29

Attached to causal_graphs#ds_40_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-40 as the defensive D295 transcriptional unit and final Science Tables S6/S7/S8 map it to one product accession, a Bas26 phage readout, display name DS-40, and a moderate-probability DUF6680 HHpred row. The pinned DefenseFinder HMM inventory records one DS-40 custom profile row. The pinned rules table has no DS-40 row, and the first-pass record does not resolve native host breadth, complete phage breadth, direct profile-to-protein correspondence, DUF6680 activity, molecular output, or endogenous DS-40 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
D295 NZ_QOYF01000088.1 GCF_003334585.1 + True False True True DefensePredictor hits 10328 11263 hypothetical protein WP_097419291.1 4.659671153870749 1.141745659485685 True True Predicted novel defense gene DS-40
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas26 2.2 pLAND 24-03-12_EV.png 2400000000 D295 24-03-14 24-03-14_RED5_D295_6236_D932.png 3 100 Y 100000 4.380211241711606 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
D295 DS-40 True
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
D295 1.0 311.0 WP_097419291.1 DUF6680 PF20385.2 DUF6680 ; Family of unknown function (DUF6680) hhpred_5944942.hhr 27.0 238.0 0.7883 2024-04-15 00:00:00
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-40 | 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-40__DS-40 | | DS-40 | Custom | 180 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-29T12:02:12Z · MINTED_TRAITMECH_ID · codex
Minted DS-40 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 D295 transcriptional-unit level because DUF6680 activity and rule rows remain unresolved, and proposals/metpo_traitmech_v339 reserves the replacement placeholder.
2026-09-29T12:02:13Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-40 system canonical_examples and left them empty because DeWeirdt et al. directly support cloned D295 assays in E. coli MG1655 and a DefenseFinder DS-40 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-40 activity. No paid research was used.