DS-42 system

traitmech:000464 · CLASS · PROPOSED

A phage defense system in which an organism possesses the three-gene DefensePredictor-discovered system 42 locus cataloged as working transcriptional unit PRO1 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
PRO1 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 661 3061 MBL fold metallo-hydrolase, hypothetical protein, hypothetical protein WP_001198055.1, WP_001024069.1, WP_249925928.1 4.870544869418898 6.906754778648663 True True Predicted novel defense gene DS-42

The final Science supplementary Table S6 maps working_id PRO1 to DS_name DS-42, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 661-3061 with product accessions WP_001198055.1, WP_001024069.1, and WP_249925928.1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 PRO1 24-04-13 24-04-13_PRO1_CBT2_AAA4_TMRA.png 5 4 Y 400000 1.0969100130080565 True LB 37

The final Science supplementary Table S7 Systems sheet reports a PRO1 assay row with a Bas1 phage readout and a -log(EOP) value of 1.097.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PRO1 DS-42 True

The final Science supplementary Table S8 maps PRO1 to replicated display name DS-42.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PRO1 3.0 363.0 WP_001198055.1 MBL hydrolase cd07731 ComA-like_MBL-fold; Competence protein ComA, ComEC and related proteins hhpred_9048500.hhr 12.0 251.0 0.998 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a high-probability MBL hydrolase HHpred hit for WP_001198055.1 in PRO1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PRO1 2.0 190.0 WP_001024069.1 Dimerization PF16892.9 CHS5_N ; Chitin biosynthesis protein CHS5 N-terminus hhpred_3514574.hhr 108.0 166.0 0.7787 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a moderate-probability CHS5_N/Dimerization HHpred hit for WP_001024069.1 in PRO1.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-42 | 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-42 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-42__DS-42A | | DS-42 | Custom | 70 |

The pinned DefenseFinder HMM inventory records DS-42__DS-42A as a custom DS-42 profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-42__DS-42B | | DS-42 | Custom | 20 |

The pinned DefenseFinder HMM inventory records DS-42__DS-42B as a custom DS-42 profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-42__DS-42C | | DS-42 | Custom | 200 |

The pinned DefenseFinder HMM inventory records DS-42__DS-42C as a custom DS-42 profile.

DS-42 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the three-gene DS-42 locus to reduced bacteriophage plaquing without resolving DS-42 component function or molecular output.

NONMECHANISTIC · The graph captures DS-42 as the validated PRO1 transcriptional unit with three product accessions, a high-probability MBL hydrolase HHpred row for WP_001198055.1, a moderate-probability CHS5_N/Dimerization HHpred row for WP_001024069.1, and three DefenseFinder DS-42 profile rows. It does not assert native host breadth, exact profile-to-protein correspondence, MBL hydrolase or CHS5_N interpretation, WP_249925928.1 function, DS-42 molecular activity, complete phage breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-42 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-42/PRO1 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 PRO1 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 661 3061 MBL fold metallo-hydrolase, hypothetical protein, hypothetical protein WP_001198055.1, WP_001024069.1, WP_249925928.1 4.870544869418898 6.906754778648663 True True Predicted novel defense gene DS-42 The final Science supplementary Table S6 maps working_id PRO1 to DS_name DS-42, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 661-3061 with product accessions WP_001198055.1, WP_001024069.1, and WP_249925928.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 PRO1 24-04-13 24-04-13_PRO1_CBT2_AAA4_TMRA.png 5 4 Y 400000 1.0969100130080565 True LB 37 The final Science supplementary Table S7 Systems sheet reports a PRO1 assay row with a Bas1 phage readout and a -log(EOP) value of 1.097.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx PRO1 DS-42 True The final Science supplementary Table S8 maps PRO1 to replicated display name DS-42.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx PRO1 3.0 363.0 WP_001198055.1 MBL hydrolase cd07731 ComA-like_MBL-fold; Competence protein ComA, ComEC and related proteins hhpred_9048500.hhr 12.0 251.0 0.998 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a high-probability MBL hydrolase HHpred hit for WP_001198055.1 in PRO1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx PRO1 2.0 190.0 WP_001024069.1 Dimerization PF16892.9 CHS5_N ; Chitin biosynthesis protein CHS5 N-terminus hhpred_3514574.hhr 108.0 166.0 0.7787 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a moderate-probability CHS5_N/Dimerization HHpred hit for WP_001024069.1 in PRO1.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-42__DS-42A | | DS-42 | Custom | 70 | The pinned DefenseFinder HMM inventory records DS-42__DS-42A as a custom DS-42 profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-42__DS-42B | | DS-42 | Custom | 20 | The pinned DefenseFinder HMM inventory records DS-42__DS-42B as a custom DS-42 profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-42__DS-42C | | DS-42 | Custom | 200 | The pinned DefenseFinder HMM inventory records DS-42__DS-42C as a custom DS-42 profile.
reduced bacteriophage plaquing confers DS-42 system METPO:2007700
DS-42-mediated phage plaquing reduction realizes the DS-42 system trait.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx PRO1 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 661 3061 MBL fold metallo-hydrolase, hypothetical protein, hypothetical protein WP_001198055.1, WP_001024069.1, WP_249925928.1 4.870544869418898 6.906754778648663 True True Predicted novel defense gene DS-42 The final Science supplementary Table S6 maps working_id PRO1 to DS_name DS-42, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 661-3061 with product accessions WP_001198055.1, WP_001024069.1, and WP_249925928.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 PRO1 24-04-13 24-04-13_PRO1_CBT2_AAA4_TMRA.png 5 4 Y 400000 1.0969100130080565 True LB 37 The final Science supplementary Table S7 Systems sheet reports a PRO1 assay row with a Bas1 phage readout and a -log(EOP) value of 1.097.
- 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-42 system is a phage defense system rdfs:subClassOf
DS-42 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-42 | 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-42 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-42 EXACT_SYNONYM · DOI:10.1126/science.adv7924
PRO1 RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-42__DS-42A RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-42__DS-42B RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-42__DS-42C 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-42 native host breadth, exact component activity, profile-to-protein mapping, MBL hydrolase and CHS5_N interpretations, WP_249925928.1 function, complete phage breadth, molecular output, and rule-level DefenseFinder criteria before minting narrower DS-42 mechanism children.

KNOWLEDGE GAP OPEN ds-42-defensefinder-model-gap · raised by codex · 2026-09-29

Attached to causal_graphs#ds_42_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-42 as the defensive PRO1 transcriptional unit and final Science Tables S6/S7/S8 map it to three product accessions, a Bas1 phage readout, display name DS-42, a high-probability MBL hydrolase HHpred row, and a moderate-probability CHS5_N/Dimerization HHpred row. The pinned DefenseFinder HMM inventory records three DS-42 custom profile rows. The pinned rules table has no DS-42 row, and the first-pass record does not resolve native host breadth, complete phage breadth, direct profile-to-protein correspondence, component activities, molecular output, or endogenous DS-42 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
PRO1 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 661 3061 MBL fold metallo-hydrolase, hypothetical protein, hypothetical protein WP_001198055.1, WP_001024069.1, WP_249925928.1 4.870544869418898 6.906754778648663 True True Predicted novel defense gene DS-42
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 PRO1 24-04-13 24-04-13_PRO1_CBT2_AAA4_TMRA.png 5 4 Y 400000 1.0969100130080565 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PRO1 DS-42 True
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PRO1 3.0 363.0 WP_001198055.1 MBL hydrolase cd07731 ComA-like_MBL-fold; Competence protein ComA, ComEC and related proteins hhpred_9048500.hhr 12.0 251.0 0.998 2024-04-15 00:00:00
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PRO1 2.0 190.0 WP_001024069.1 Dimerization PF16892.9 CHS5_N ; Chitin biosynthesis protein CHS5 N-terminus hhpred_3514574.hhr 108.0 166.0 0.7787 2024-04-15 00:00:00
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-42 | 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-42__DS-42A | | DS-42 | Custom | 70 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-42__DS-42B | | DS-42 | Custom | 20 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-42__DS-42C | | DS-42 | Custom | 200 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-29T13:30:52Z · MINTED_TRAITMECH_ID · codex
Minted DS-42 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 PRO1 transcriptional-unit level because component activities and rule rows remain unresolved, and proposals/metpo_traitmech_v341 reserves the replacement placeholder.
2026-09-29T13:30:53Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-42 system canonical_examples and left them empty because DeWeirdt et al. directly support cloned PRO1 assays in E. coli MG1655 and a DefenseFinder DS-42 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-42 activity. No paid research was used.