DS-38 system

traitmech:000460 · CLASS · PROPOSED

A phage defense system in which an organism possesses the single-gene DefensePredictor-discovered system 38 locus cataloged as working transcriptional unit HEP2 and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing.

Trait evidence (10)

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
HEP2 NZ_QOYR01000034.1 GCF_003333645.1 - True False True True DefensePredictor hits 8089 9189 hypothetical protein WP_001313577.1 8.026493157403 2.649821696202418 True True Predicted novel defense gene DS-38

The final Science supplementary Table S6 maps working_id HEP2 to DS_name DS-38, marks the cloned transcriptional unit as defensive, and records NZ_QOYR01000034.1 positions 8089-9189 with product accession WP_001313577.1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas25 2.2 pLAND 24-03-12_EV.png 500000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 5.698970004336019 True LB 37

The final Science supplementary Table S7 Systems sheet reports an HEP2 assay row with a Bas25 phage readout and a -log(EOP) value of 5.699.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas19 2.2 pLAND 24-03-12_EV.png 15000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 4.176091259055681 True LB 37

The final Science supplementary Table S7 Systems sheet reports an HEP2 assay row with a Bas19 phage readout and a -log(EOP) value of 4.176.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
HEP2 DS-38 True

The final Science supplementary Table S8 maps HEP2 to replicated display name DS-38.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
HEP2 1.0 366.0 WP_001313577.1 ZF 8SSU_A Transcriptional repressor CTCF,LIM domain-binding protein 1; PROTEIN-DNA COMPLEX, DNA BINDING PROTEIN, transcription factor, zinc fingers, insulator/chromatin architecture, transcription-dna complex, TRANSCRIPTION hhpred_7553560.hhr 206.0 364.0 0.9902 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a high-probability zinc-finger HHpred hit for WP_001313577.1 in HEP2.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
HEP2 1.0 366.0 WP_001313577.1 HEPN PF05168.18 HEPN ; HEPN domain hhpred_7553560.hhr 22.0 153.0 0.9662 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a high-probability HEPN HHpred hit for WP_001313577.1 in HEP2.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-38 | 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-38 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-38__DS-38 | | DS-38 | Custom | 200 |

The pinned DefenseFinder HMM inventory records DS-38__DS-38 as a custom DS-38 profile.

DS-38 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the single-gene DS-38 locus to reduced bacteriophage plaquing without resolving DS-38 component function or molecular output.

NONMECHANISTIC · The graph captures DS-38 as the validated HEP2 transcriptional unit with one product accession, high-probability zinc-finger and HEPN HHpred rows for WP_001313577.1, and one DefenseFinder DS-38 profile row. It does not assert exact profile-to-protein correspondence, HEPN ribonuclease activity, zinc-finger DNA-binding activity, native host breadth, DS-38 molecular output, complete phage breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-38 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-38/HEP2 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 HEP2 NZ_QOYR01000034.1 GCF_003333645.1 - True False True True DefensePredictor hits 8089 9189 hypothetical protein WP_001313577.1 8.026493157403 2.649821696202418 True True Predicted novel defense gene DS-38 The final Science supplementary Table S6 maps working_id HEP2 to DS_name DS-38, marks the cloned transcriptional unit as defensive, and records NZ_QOYR01000034.1 positions 8089-9189 with product accession WP_001313577.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas25 2.2 pLAND 24-03-12_EV.png 500000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 5.698970004336019 True LB 37 The final Science supplementary Table S7 Systems sheet reports an HEP2 assay row with a Bas25 phage readout and a -log(EOP) value of 5.699.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas19 2.2 pLAND 24-03-12_EV.png 15000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 4.176091259055681 True LB 37 The final Science supplementary Table S7 Systems sheet reports an HEP2 assay row with a Bas19 phage readout and a -log(EOP) value of 4.176.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx HEP2 DS-38 True The final Science supplementary Table S8 maps HEP2 to replicated display name DS-38.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx HEP2 1.0 366.0 WP_001313577.1 ZF 8SSU_A Transcriptional repressor CTCF,LIM domain-binding protein 1; PROTEIN-DNA COMPLEX, DNA BINDING PROTEIN, transcription factor, zinc fingers, insulator/chromatin architecture, transcription-dna complex, TRANSCRIPTION hhpred_7553560.hhr 206.0 364.0 0.9902 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a high-probability zinc-finger HHpred hit for WP_001313577.1 in HEP2.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx HEP2 1.0 366.0 WP_001313577.1 HEPN PF05168.18 HEPN ; HEPN domain hhpred_7553560.hhr 22.0 153.0 0.9662 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a high-probability HEPN HHpred hit for WP_001313577.1 in HEP2.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-38__DS-38 | | DS-38 | Custom | 200 | The pinned DefenseFinder HMM inventory records DS-38__DS-38 as a custom DS-38 profile.
reduced bacteriophage plaquing confers DS-38 system METPO:2007700
DS-38-mediated phage plaquing reduction realizes the DS-38 system trait.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx HEP2 NZ_QOYR01000034.1 GCF_003333645.1 - True False True True DefensePredictor hits 8089 9189 hypothetical protein WP_001313577.1 8.026493157403 2.649821696202418 True True Predicted novel defense gene DS-38 The final Science supplementary Table S6 maps working_id HEP2 to DS_name DS-38, marks the cloned transcriptional unit as defensive, and records NZ_QOYR01000034.1 positions 8089-9189 with product accession WP_001313577.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas25 2.2 pLAND 24-03-12_EV.png 500000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 5.698970004336019 True LB 37 The final Science supplementary Table S7 Systems sheet reports an HEP2 assay row with a Bas25 phage readout and a -log(EOP) value of 5.699.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas19 2.2 pLAND 24-03-12_EV.png 15000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 4.176091259055681 True LB 37 The final Science supplementary Table S7 Systems sheet reports an HEP2 assay row with a Bas19 phage readout and a -log(EOP) value of 4.176.
- 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-38 system is a phage defense system rdfs:subClassOf
DS-38 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-38 | 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-38 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-38 EXACT_SYNONYM · DOI:10.1126/science.adv7924
HEP2 RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-38__DS-38 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-38 native host breadth, exact component activity, profile-to-protein mapping, HEPN ribonuclease interpretation, zinc-finger DNA-binding interpretation, complete phage breadth, molecular output, and rule-level DefenseFinder criteria before minting narrower DS-38 mechanism children.

KNOWLEDGE GAP OPEN ds-38-defensefinder-model-gap · raised by codex · 2026-09-29

Attached to causal_graphs#ds_38_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-38 as the defensive HEP2 transcriptional unit and final Science Tables S6/S7/S8 map it to one product accession, Bas25 and Bas19 phage readouts, display name DS-38, and high-probability HEPN and zinc-finger HHpred rows. The pinned DefenseFinder HMM inventory records one DS-38 custom profile row. The pinned rules table has no DS-38 row, and the first-pass record does not resolve native host breadth, complete phage breadth, direct profile-to-protein correspondence, HEPN ribonuclease activity, zinc-finger DNA-binding activity, molecular output, or endogenous DS-38 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
HEP2 NZ_QOYR01000034.1 GCF_003333645.1 - True False True True DefensePredictor hits 8089 9189 hypothetical protein WP_001313577.1 8.026493157403 2.649821696202418 True True Predicted novel defense gene DS-38
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas25 2.2 pLAND 24-03-12_EV.png 500000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 5.698970004336019 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas19 2.2 pLAND 24-03-12_EV.png 15000 HEP2 24-03-15 24-03-15_GPEH_HEP2_PDO1_PDP6.png 0 1 1 4.176091259055681 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
HEP2 DS-38 True
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
HEP2 1.0 366.0 WP_001313577.1 ZF 8SSU_A Transcriptional repressor CTCF,LIM domain-binding protein 1; PROTEIN-DNA COMPLEX, DNA BINDING PROTEIN, transcription factor, zinc fingers, insulator/chromatin architecture, transcription-dna complex, TRANSCRIPTION hhpred_7553560.hhr 206.0 364.0 0.9902 2024-04-15 00:00:00
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
HEP2 1.0 366.0 WP_001313577.1 HEPN PF05168.18 HEPN ; HEPN domain hhpred_7553560.hhr 22.0 153.0 0.9662 2024-04-15 00:00:00
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-38 | 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-38__DS-38 | | DS-38 | Custom | 200 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-29T10:59:36Z · MINTED_TRAITMECH_ID · codex
Minted DS-38 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 HEP2 transcriptional-unit level because the HEPN and zinc-finger rows and rule rows remain unresolved, and proposals/metpo_traitmech_v337 reserves the replacement placeholder.
2026-09-29T10:59:37Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-38 system canonical_examples and left them empty because DeWeirdt et al. directly support cloned HEP2 assays in E. coli MG1655 and a DefenseFinder DS-38 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-38 activity. No paid research was used.