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PADLOC-DB

About

This repo contains the latest version of the HMMs and system models used by PADLOC. The latest version of this database can be downloaded by running padloc --db-update.

The following document describes each field of hmm_meta.txt and sys_meta.txt, and how you can use your own HMMs and system models with PADLOC.

Citation

If you use PADLOC or PADLOC-DB please cite:

Payne, L.J., Todeschini, T.C., Wu, Y., Perry, B.J., Ronson, C.W., Fineran, P.C., Nobrega, F.L., Jackson, S.A. (2021) Identification and classification of antiviral defence systems in bacteria and archaea with PADLOC reveals new system types. Nucleic Acids Research, 49, 10868-10878. doi: https://doi.org/10/gzgh

The HMMs in PADLOC-DB were built/curated using data from various sources, we encourage you to also give credit to these groups by citing them too.

System models

System models are written using YAML syntax:

---
maximum_separation: 4       <- Number of unrelated genes allowed to separate each component.
minimum_core: 4             <- Number of core genes that need to be present.
minimum_total: 5            <- Number of total genes that need to be present.
core_genes:                 <- Genes that are generally considered essential.
  - GenA
  - GenB
  - GenC
  - GenD
optional_genes:             <- Genes that are not always present.
  - GenX
  - GenY
prohibited_genes:           <- Genes that cannot be present.
  - GenZ
...

HMM metadata (hmm_meta.txt)

Compulsory fields

These fields must be filled out for use with PADLOC.

Field Example Description
hmm.accession PDLC00001 A unique identifier for each padlocDB HMM.
hmm.name GajA_6 Another unique identifier for each HMM. If the HMM is from an external database, the original ID from that database is preferred.
hmm.description Predicted ATPase A one line description of the HMM e.g. describing protein function or domains.
protein.name PemK|MazF The name of the protein that the HMM represents. Multiple protein names are separated by '|'. Capitalisation of the first letter is preferred. These are the names that are referenced in the system models.
e.value.threshold 1e-05 The minimum E-value allowed when reporting hits.
hmm.coverage.threshold 0.3 The proportion of the HMM that must contribute to the HMM/target alignment when reporting hits.
target.coverage.threshold 0.3 The proportion of the target that must contribute to the HMM/target alignment when reporting hits.
comment NA Other information that is relevant. This may include comments from the original database where applicable.

Optional fields

These fields are for reference only, and are not strictly required by PADLOC.

Field Example Description
secondary.name CRISPR-accessory A secondary identifier that can be referred to in the system definition for groups of proteins rather than individual protein names
system DISARM, RESTRICTION MODIFICATION The category of defence system to which the HMM belongs. Multiple system names are separated by ', '. The full system name is used where reasonable.
author Payne LJ, Jackson SA Author(s) of the entry. If the HMM is from an external database, crediting the original author is preferred. If the HMM is from a study where an author was not explicity credited, authorship is attributed to the first author of the study. Multiple authors are separated by ', '.
hmm.nseq 49 The number of sequences that contribute to the HMM.
hmm.length 120 The length of the the HMM.
literature.ref 10/f2wkj3 The DOI for the literature that implies that the HMM or underlying proteins belong to the protein/defence system. Multiple references are separated by ', '. DOIs can be resolved at doi.org.
database.ref PFAM; PF06527 Reference to the original accession of the alignment/HMM if it was taken from an external database, e.g. PFAM, COG, etc. Includes the name of the database and the identifier separated by '; '.

System metadata (sys_meta.txt)

Compulsory fields

Field Example Description
yaml.name druantia_type_I The exact name of the yaml file that corresponds with the system type (without the .yaml extension)
search T Set to TRUE or FALSE (or T / F) to determine whether the system is searched or not.
comment NA Other information that is relevant.

Optional fields

Field Example Description
system.name Druantia The name of the system
type type I The subtype of the system.

Adding to the database

Additional HMMs and system models can be added directly to your copy of this database, or a separate database can be set up in the same way as this one.

Additional HMMs can be added to the hmm/ directory, hmm_meta.txt also needs to be updated to include metadata for the new HMMs. When using with PADLOC, these HMMs need to be concatenated into a single file in the hmm/ directory called padlocdb.hmm.

Additional system models can be added to the sys/ directory, sys_meta.txt should also be updated to include metadata for the new models.

References

The HMMs in PADLOC-DB were built/curated using data from various sources, we encourage you to also give credit to these groups by citing them too:

Doron, S., Melamed, S., Ofir, G., Leavitt, A., Lopatina, A., Keren, M., Amitai, G. and Sorek, R. (2018) Systematic discovery of antiphage defense systems in the microbial pangenome. Science, 359, eaar4120. doi: 10/ggqhzm

Millman, A., Melamed, S., Amitai, G. and Sorek, R. (2020) Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. Nature Microbiology, 5, 1608–1615. doi: 10/gg84nk

Couvin, D., Bernheim, A., Toffano-Nioche, C., Touchon, M., Michalik, J., Néron, B., Rocha, E. P. C., Vergnaud, G., Gautheret, D. and Pourcel, C. (2018) CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins. Nucleic Acids Res, 46, W246–W251. doi: 10/ggdjdf

Makarova, K. S., Wolf, Y. I., Iranzo, J., Shmakov, S. A., Alkhnbashi, O. S., Brouns, S. J. J., Charpentier, E., Cheng, D., Haft, D. H., Horvath, P., et al. (2020) Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants. Nat Rev Microbiol, 18, 67–83. doi: 10/ggkfgj

Shah, S. A., Alkhnbashi, O. S., Behler, J., Han, W., She, Q., Hess, W. R., Garrett, R. A. and Backofen, R. (2019) Comprehensive search for accessory proteins encoded with archaeal and bacterial type III CRISPR-cas gene cassettes reveals 39 new cas gene families. RNA Biology, 16, 530–542. doi: 10/ggqv9p

Shmakov, S. A., Makarova, K. S., Wolf, Y. I., Severinov, K. V. and Koonin, E. V. (2018) Systematic prediction of genes functionally linked to CRISPR-Cas systems by gene neighborhood analysis. PNAS, 115, E5307–E5316. doi: 10/gdpqwq

Russel, J., Pinilla-Redondo, R., Mayo-Muñoz, D., Shah, S. A. and Sørensen, S. J. (2020) CRISPRCasTyper: Automated Identification, Annotation, and Classification of CRISPR-Cas Loci. The CRISPR Journal, 3, 462–469. doi: 10/gshm

Gao, L., Altae-Tran, H., Böhning, F., Makarova, K. S., Segel, M., Schmid-Burgk, J. L., Koob, J., Wolf, Y. I., Koonin, E. V. and Zhang, F. (2020) Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science, 369, 1077–1084. doi: 10/gpsx

Makarova, K. S., Timinskas, A., Wolf, Y. I., Gussow, A. B., Siksnys, V., Venclovas, Č. and Koonin, E. V. (2020) Evolutionary and functional classification of the CARF domain superfamily, key sensors in prokaryotic antivirus defense. Nucleic Acids Res, 48, 8828–8847. doi: 10/gg7qx6

Bouchard, J. D., Dion, E., Bissonnette, F. and Moineau, S. (2002) Characterization of the Two-Component Abortive Phage Infection Mechanism AbiT from Lactococcus lactis. Journal of Bacteriology, 184, 6325–6332. doi: 10/btq97w

Parma, D. H., Snyder, M., Sobolevski, S., Nawroz, M., Brody, E. and Gold, L. (1992) The Rex system of bacteriophage lambda: tolerance and altruistic cell death. Genes Dev., 6, 497–510. doi: 10/b9xpsb

Jabbar, M. A. and Snyder, L. (1984) Genetic and physiological studies of an Escherichia coli locus that restricts polynucleotide kinase- and RNA ligase-deficient mutants of bacteriophage T4. Journal of Virology, 51, 522–529. doi: 10/gndc4t

Cram, D., Ray, A. and Skurray, R. (1984) Molecular analysis of F plasmid pif region specifying abortive infection of T7 phage. Mol Gen Genet, 197, 137–142. doi: 10/fg7s8g

Smith, H. S., Pizer, L. I., Pylkas, L. and Lederberg, S. (1969) Abortive Infection of Shigella dysenteriae P2 by T2 Bacteriophage. Journal of Virology, 4, 162–168. doi: 10/gndc4r

Dai, G., Su, P., Allison, G. E., Geller, B. L., Zhu, P., Kim, W. S. and Dunn, N. W. (2001) Molecular Characterization of a New Abortive Infection System (AbiU) from Lactococcus lactisLL51-1. Applied and Environmental Microbiology, 67, 5225–5232. doi: 10/cwbxdg

Lindahl, G., Sironi, G., Bialy, H. and Calendar, R. (1970) Bacteriophage Lambda; Abortive Infection of Bacteria Lysogenic for Phage P2. PNAS, 66, 587–594. doi: 10/fkgq7x

Bergsland, K. J., Kao, C., Yu, Y. T. N., Gulati, R. and Snyder, L. (1990) A site in the T4 bacteriophage major head protein gene that can promote the inhibition of all translation in Escherichia coli. Journal of Molecular Biology, 213, 477–494. doi: 10/fv36tb

Durmaz, E. and Klaenhammer, T. R. (2007) Abortive Phage Resistance Mechanism AbiZ Speeds the Lysis Clock To Cause Premature Lysis of Phage-Infected Lactococcus lactis. Journal of Bacteriology, 189, 1417–1425. doi: 10/dnndhw

Haaber, J., Moineau, S., Fortier, L. C. and Hammer, K. (2008) AbiV, a Novel Antiphage Abortive Infection Mechanism on the Chromosome of Lactococcus lactis subsp. cremoris MG1363. Applied and Environmental Microbiology, 74, 6528–6537. doi: 10/cnwcq7

Emond, E., Dion, E., Walker, S. A., Vedamuthu, E.R., Kondo, J.K. and Moineau, S. (1998) AbiQ, an Abortive Infection Mechanism fromLactococcus lactis. Applied and Environmental Microbiology, 64, 4748–4756. doi: 10/gndc4p

Domingues, S., Chopin, A., Ehrlich, S. D. and Chopin, M. C. (2004) The Lactococcal Abortive Phage Infection System AbiP Prevents both Phage DNA Replication and Temporal Transcription Switch. Journal of Bacteriology, 186, 713–721. doi: 10/bjjwc6

Prevots, F. and Ritzenthaler, P. (1998) Complete Sequence of the New Lactococcal Abortive Phage Resistance Gene abiO. Journal of Dairy Science, 81, 1483–1485. doi: 10/cg69rg

Prévots, F., Tolou, S., Delpech, B., Kaghad, M. and Daloyau, M. (1998) Nucleotide sequence and analysis of the new chromosomal abortive infection gene abiN of Lactococcus lactis subsp. cremoris S114. FEMS Microbiology Letters, 159, 331–336. doi: 10/c94sd6

Deng, Y. M., Liu, C. Q. and W. Dunn, N. (1999) Genetic organization and functional analysis of a novel phage abortive infection system, AbiL, from Lactococcus lactis. Journal of Biotechnology, 67, 135–149. doi: 10/bwc9k8

Emond, E., Holler, B. J., Boucher, I., Vandenbergh, P. A., Vedamuthu, E. R., Kondo, J. K. and Moineau, S. (1997) Phenotypic and genetic characterization of the bacteriophage abortive infection mechanism AbiK from Lactococcus lactis. Applied and Environmental Microbiology, 63, 1274–1283. doi: 10/gndc4n

Deng, Y. M., Harvey, M. L., Liu, C. Q. and Dunn, N. W. (1997) A novel plasmid-encoded phage abortive infection system from Lactococcus lactis biovar. diacetylactis. FEMS Microbiology Letters, 146, 149–154. doi: 10/d24tcq

Su, P., Harvey, M., Im, H. J. and Dunn, N. W. (1997) Isolation, cloning and characterisation of the abiI gene from Lactococcus lactis subsp. lactis M138 encoding abortive phage infection. Journal of Biotechnology, 54, 95–104. doi: 10/ckwmpp

Prévots, F., Daloyau, M., Bonin, O., Dumont, X. and Tolou, S. (1996) Cloning and sequencing of the novel abortive infection gene abiH of Lactococcus lactis ssp. lactis biovar. diacetylactis S94. FEMS Microbiology Letters, 142, 295–299. doi: 10/dvjcb5

O’Connor, L., Coffey, A., Daly, C. and Fitzgerald, G. F. (1996) AbiG, a genotypically novel abortive infection mechanism encoded by plasmid pCI750 of Lactococcus lactis subsp. cremoris UC653. Applied and Environmental Microbiology, 62, 3075–3082. doi: 10/gndc4m

Garvey, P., Fitzgerald, G. F. and Hill, C. (1995) Cloning and DNA sequence analysis of two abortive infection phage resistance determinants from the lactococcal plasmid pNP40. Applied and Environmental Microbiology, 61, 4321–4328. doi: 10/gndc3x

Dy, R. L., Przybilski, R., Semeijn, K., Salmond, G. P. C. and Fineran, P. C. (2014) A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism. Nucleic Acids Research, 42, 4590–4605. doi: 10/f5zkmw

McLandsborough, L.A., Kolaetis, K. M., Requena, T. and McKay, L. L. (1995) Cloning and characterization of the abortive infection genetic determinant abiD isolated from pBF61 of Lactococcus lactis subsp. lactis KR5. Applied and Environmental Microbiology, 61, 2023–2026. doi: 10/gndc4j

Garvey, P., Fitzgerald, G. F. and Hill, C. (1995) Cloning and DNA sequence analysis of two abortive infection phage resistance determinants from the lactococcal plasmid pNP40. Applied and Environmental Microbiology, 61, 4321–4328. doi: 10/gndc3x

Anba, J., Bidnenko, E., Hillier, A., Ehrlich, D. and Chopin, M. C. (1995) Characterization of the lactococcal abiD1 gene coding for phage abortive infection. Journal of Bacteriology, 177, 3818–3823. doi: 10/gndc3w

Durmaz, E., Higgins, D. L. and Klaenhammer, T. R. (1992) Molecular characterization of a second abortive phage resistance gene present in Lactococcus lactis subsp. lactis ME2. Journal of Bacteriology, 174, 7463–7469. doi: 10/gndc3v

Parreira, R., Ehrlich, S. D. and Chopin, M. C. (1996) Dramatic decay of phage transcripts in lactococcal cells carrying the abortive infection determinant AbiB. Molecular Microbiology, 19, 221–230. doi: 10/b835bf

Cluzel, P. J., Chopin, A., Ehrlich, S. D. and Chopin, M. C. (1991) Phage abortive infection mechanism from Lactococcus lactis subsp. lactis, expression of which is mediated by an Iso-ISS1 element. Applied and Environmental Microbiology, 57, 3547–3551. doi: 10/gndc3t

Dinsmore, P. K. and Klaenhammer, T. R. (1994) Phenotypic Consequences of Altering the Copy Number of abiA, a Gene Responsible for Aborting Bacteriophage Infections in Lactococcus lactis. Applied and Environmental Microbiology, 60, 1129–1136. doi: 10/gndc3s

Owen, S. V., Wenner, N., Dulberger, C. L., Rodwell, E. V., Bowers-Barnard, A., Quinones-Olvera, N., Rigden, D. J., Rubin, E. J., Garner, E. C., Baym, M., et al. (2021) Prophages encode phage-defense systems with cognate self-immunity. Cell Host & Microbe, 29, 1620-1633. doi: 10/g29b

Bari, S. M. N., Chou-Zheng, L., Howell, O., Cater, K., Dandu, V. S., Thomas, A., Aslan, B., and Hatoum-Aslan, A. (2021). A unique mode of nucleic acid immunity performed by a single multifunctional enzyme. bioRxiv. doi: 10/gkw6wr

Burroughs A. M., Ando Y., Aravind L. (2014) New perspectives on the diversification of the RNA interference system: insights from comparative genomics and small RNA sequencing. WIREs RNA. 5, 141–181. doi: 10/gfkh7c

Makarova, K. S., Wolf, Y. I., van der Oost, J., and Koonin, E. V. (2009). Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements. Biol Direct, 4, 29. doi: 10/cvfhm6

Burroughs, A. M., Iyer, L. M., and Aravind, L. (2013). Two novel PIWI families: roles in inter-genomic conflicts in bacteria and Mediator-dependent modulation of transcription in eukaryotes. Biology Direct 8, 13. doi: 10/f46qcd

Zeng, Z., Chen, Y., Pinilla-Redondo, R., Shah, S. A., Zhao, F., Wang, C., Hu, Z., Zhang, C., Whitaker, R. J., She, Q., et al. (2021). A short prokaryotic argonaute cooperates with membrane effector to confer antiviral defense. bioRxiv. doi: 10//hgr9

Mestre, M. R., González-Delgado, A., Gutiérrez-Rus, L. I., Martínez-Abarca, F., and Toro, N. (2020). Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems. Nucleic Acids Research, 48, 12632–12647. doi: 10/fzk3

Millman, A., Bernheim, A., Stokar-Avihail, A., Fedorenko, T., Voichek, M., Leavitt, A., Oppenheimer-Shaanan, Y., and Sorek, R. (2020). Bacterial Retrons Function In Anti-Phage Defense. Cell, 183, 1551-1561.e12. doi: 10/ghjct3

Bernheim, A., Millman, A., Ofir, G., Meitav, G., Avraham, C., Shomar, H., Rosenberg, M. M., Tal, N., Melamed, S., Amitai, G., et al. (2021). Prokaryotic viperins produce diverse antiviral molecules. Nature, 589, 120–124. doi: 10/d9ss

Goldfarb, T., Sberro, H., Weinstock, E., Cohen, O., Doron, S., Charpak‐Amikam, Y., Afik, S., Ofir, G., and Sorek, R. (2015). BREX is a novel phage resistance system widespread in microbial genomes. EMBO J, 34, 169–183. doi: 10/f2wkj3

Ofir, G., Melamed, S., Sberro, H., Mukamel, Z., Silverman, S., Yaakov, G., Doron, S., and Sorek, R. (2018). DISARM is a widespread bacterial defence system with broad anti-phage activities. Nat Microbiol, 3, 90–98. doi: 10/ggnszb

Yuan, Y., Hutinet, G., Valera, J. G., Hu, J., Hillebrand, R., Gustafson, A., Iwata-Reuyl, D., Dedon, P. C., and de Crécy-Lagard, V. (2018). Identification of the minimal bacterial 2′-deoxy-7-amido-7-deazaguanine synthesis machinery. Molecular Microbiology, 110, 469–483. doi: 10/gfft6b

Thiaville, J. J., Kellner, S. M., Yuan, Y., Hutinet, G., Thiaville, P. C., Jumpathong, W., Mohapatra, S., Brochier-Armanet, C., Letarov, A. V., Hillebrand, R., et al. (2016). Novel genomic island modifies DNA with 7-deazaguanine derivatives. Proc Natl Acad Sci USA, 113, E1452–E1459. doi: 10/ggr4f7

Tong, T., Chen, S., Wang, L., Tang, Y., Ryu, J. Y., Jiang, S., Wu, X., Chen, C., Luo, J., Deng, Z., et al. (2018). Occurrence, evolution, and functions of DNA phosphorothioate epigenetics in bacteria. Proc Natl Acad Sci USA, 115, E2988–E2996. doi: 10/gdbj2n

Xu, T., Yao, F., Zhou, X., Deng, Z., and You, D. (2010). A novel host-specific restriction system associated with DNA backbone S-modification in Salmonella. Nucleic Acids Research, 38, 7133–7141. doi: 10/d5zqcp

Xiong, L., Liu, S., Chen, S., Xiao, Y., Zhu, B., Gao, Y., Zhang, Y., Chen, B., Luo, J., Deng, Z., et al. (2019). A new type of DNA phosphorothioation-based antiviral system in archaea. Nat Commun, 10, 1688. 10/ggctjz

Xiong, X., Wu, G., Wei, Y., Liu, L., Zhang, Y., Su, R., Jiang, X., Li, M., Gao, H., Tian, X., et al. (2020). SspABCD–SspE is a phosphorothioation-sensing bacterial defence system with broad anti-phage activities. Nat Microbiol, 5, 917–928. 10/ggq8nb

Wang, S., Wan, M., Huang, R., Zhang, Y., Xie, Y., Wei, Y., Ahmad, M., Wu, D., Hong, Y., Deng, Z., et al. (2021). SspABCD-SspFGH Constitutes a New Type of DNA Phosphorothioate-Based Bacterial Defense System. MBio, 12, e00613-21. 10/gbsw

The relevant refences for individual HMMs can be found by inspecting the hmm_meta.txt file provided with PADLOC-DB.

License

This software and data is available as open source under the terms of the MIT License.

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