DS-35 system

traitmech:000458 · CLASS · PROPOSED

A phage defense system in which an organism possesses the single-gene DefensePredictor-discovered system 35 locus cataloged as working transcriptional unit RED5 and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing.

Trait evidence (9)

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
RED5 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 25863 26705 hypothetical protein WP_087906371.1 8.022232609988304 2.666159259393051 True True Remote defense homolog DS-35

The final Science supplementary Table S6 maps working_id RED5 to DS_name DS-35, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 25863-26705 with product accession WP_087906371.1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
RB69 2.1 pLAND 24-03-12_EV.png 200000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 0 1 1 5.301029995663981 True LB 37

The final Science supplementary Table S7 reports a RED5 assay row with an RB69 phage readout and a -log(EOP) value of 5.301.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
T4 2.1 pLAND 24-03-12_EV.png 200000000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 2 10 1000 5.301029995663981 True LB 37

The final Science supplementary Table S7 reports a RED5 assay row with a T4 phage readout and a -log(EOP) value of 5.301.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
RED5 DS-35 True

The final Science supplementary Table S8 maps RED5 to replicated display name DS-35.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
RED5 1.0 280.0 WP_087906371.1 PDDEXK PF18742.5 DpnII-MboI ; REase_DpnII-MboI hhpred_9496458.hhr 142.0 278.0 1.0 2024-04-15 00:00:00 346-348 333.0

The final Science supplementary Table S8 reports a high-probability PDDEXK HHpred hit for WP_087906371.1 in RED5.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-35 | 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-35 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-35__DS-35 | | DS-35 | Custom | 100 |

The pinned DefenseFinder HMM inventory records DS-35__DS-35 as a custom DS-35 profile.

DS-35 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the single-gene DS-35 locus to reduced bacteriophage plaquing without resolving DS-35 component function or molecular output.

NONMECHANISTIC · The graph captures DS-35 as the validated RED5 transcriptional unit with one product accession, one high-probability PDDEXK HHpred row for WP_087906371.1 in Table S8, and one DefenseFinder DS-35 profile row. It does not assert exact profile-to-protein correspondence, PDDEXK domain interpretation, nuclease chemistry, native host breadth, DS-35 molecular output, complete phage breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-35 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-35/RED5 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 RED5 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 25863 26705 hypothetical protein WP_087906371.1 8.022232609988304 2.666159259393051 True True Remote defense homolog DS-35 The final Science supplementary Table S6 maps working_id RED5 to DS_name DS-35, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 25863-26705 with product accession WP_087906371.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx RB69 2.1 pLAND 24-03-12_EV.png 200000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 0 1 1 5.301029995663981 True LB 37 The final Science supplementary Table S7 reports a RED5 assay row with an RB69 phage readout and a -log(EOP) value of 5.301.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx T4 2.1 pLAND 24-03-12_EV.png 200000000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 2 10 1000 5.301029995663981 True LB 37 The final Science supplementary Table S7 reports a RED5 assay row with a T4 phage readout and a -log(EOP) value of 5.301.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx RED5 DS-35 True The final Science supplementary Table S8 maps RED5 to replicated display name DS-35.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx RED5 1.0 280.0 WP_087906371.1 PDDEXK PF18742.5 DpnII-MboI ; REase_DpnII-MboI hhpred_9496458.hhr 142.0 278.0 1.0 2024-04-15 00:00:00 346-348 333.0 The final Science supplementary Table S8 reports a high-probability PDDEXK HHpred hit for WP_087906371.1 in RED5.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-35__DS-35 | | DS-35 | Custom | 100 | The pinned DefenseFinder HMM inventory records DS-35__DS-35 as a custom DS-35 profile.
reduced bacteriophage plaquing confers DS-35 system METPO:2007700
DS-35-mediated phage plaquing reduction realizes the DS-35 system trait.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx RED5 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 25863 26705 hypothetical protein WP_087906371.1 8.022232609988304 2.666159259393051 True True Remote defense homolog DS-35 The final Science supplementary Table S6 maps working_id RED5 to DS_name DS-35, marks the cloned transcriptional unit as defensive, and records NZ_QOXO01000016.1 positions 25863-26705 with product accession WP_087906371.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx RB69 2.1 pLAND 24-03-12_EV.png 200000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 0 1 1 5.301029995663981 True LB 37 The final Science supplementary Table S7 reports a RED5 assay row with an RB69 phage readout and a -log(EOP) value of 5.301.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx T4 2.1 pLAND 24-03-12_EV.png 200000000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 2 10 1000 5.301029995663981 True LB 37 The final Science supplementary Table S7 reports a RED5 assay row with a T4 phage readout and a -log(EOP) value of 5.301.
- 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-35 system is a phage defense system rdfs:subClassOf
DS-35 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-35 | 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-35 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-35 EXACT_SYNONYM · DOI:10.1126/science.adv7924
RED5 RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-35__DS-35 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-35 native host breadth, exact component activity, profile-to-protein mapping, PDDEXK HHpred-domain interpretation, nuclease chemistry, complete phage breadth, molecular output, and rule-level DefenseFinder criteria before minting narrower DS-35 mechanism children.

KNOWLEDGE GAP OPEN ds-35-defensefinder-model-gap · raised by codex · 2026-09-29

Attached to causal_graphs#ds_35_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-35 as the defensive RED5 transcriptional unit and final Science Tables S6/S7/S8 map it to one product accession, RB69 and T4 phage readouts, display name DS-35, and one PDDEXK HHpred row. The pinned DefenseFinder HMM inventory records one DS-35 custom profile row. The pinned rules table has no DS-35 row, and the first-pass record does not resolve native host breadth, complete phage breadth, direct profile-to-protein correspondence, PDDEXK domain interpretation, nuclease chemistry, molecular output, or endogenous DS-35 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
RED5 NZ_QOXO01000016.1 GCF_003334005.1 - True False True True DefensePredictor hits 25863 26705 hypothetical protein WP_087906371.1 8.022232609988304 2.666159259393051 True True Remote defense homolog DS-35
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
RB69 2.1 pLAND 24-03-12_EV.png 200000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 0 1 1 5.301029995663981 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
T4 2.1 pLAND 24-03-12_EV.png 200000000 RED5 24-03-14 24-03-14_RED5_TNEC_6236_RED2.png 2 10 1000 5.301029995663981 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
RED5 DS-35 True
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
RED5 1.0 280.0 WP_087906371.1 PDDEXK PF18742.5 DpnII-MboI ; REase_DpnII-MboI hhpred_9496458.hhr 142.0 278.0 1.0 2024-04-15 00:00:00 346-348 333.0
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-35 | 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-35__DS-35 | | DS-35 | Custom | 100 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-29T09:12:09Z · MINTED_TRAITMECH_ID · codex
Minted DS-35 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 RED5 transcriptional-unit level because PDDEXK activity and rule rows remain unresolved, and proposals/metpo_traitmech_v335 reserves the replacement placeholder.
2026-09-29T09:12:10Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-35 system canonical_examples and left them empty because DeWeirdt et al. directly support cloned RED5 assays in E. coli MG1655 and a DefenseFinder DS-35 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-35 activity. No paid research was used.