DOI: 10.5061/dryad.rv15dv4cb
title: “Tear down that wall” – updating the vocabulary of phage and bacterial lytic proteins

description: Lytic enzymes (often called lysins) break down the peptidoglycan, which in
 turn results in the death of bacteria. In consequence, they become one of
 the most promising alternatives to antibiotics. Such enzymes have been in
 the research spotlight and some of them have been proven to be effective
 and safe. The aim of this work was to gather the scattered data on
 functional and structural diversity of lysins, as well as available
 bioinformatic tools and data repositories used in studies of these
 proteins.  In the introductory part of this paper, we
 disambiguate the terminology of lytic proteins, which, over the years, has
 grown to be inconsistent in different branches of science, and delineate
 major lysin groups. We also review the databases and programs, which can
 be harnessed in lysin studies, and put particular emphasis on repositories
 of Hidden Markov Models. Finally, we describe a comprehensive,
 meticulously curated set of lysin proteins, protein families and domains,
 and sort them into clusters that reflect major families. Thus this work is
 a guide through a convoluted tangle of terms, concepts, databases, models,
 approaches and programs used to detect lytic enzymes.
description: Original data were retrieved from: http://biotechlab.fudan.edu.cn/database/EnzyBase https://www.uniprot.org   Family/Domain databases: http://eggnog5.embl.de (ver. 5.0) http://pfam.xfam.org (ver. 33.0) http://dmk-brain.ecn.uiowa.edu/pVOGs (accesed 01.02.2020) https://vogdb.org (ver. vog99)   Proteins clustering (de-replication, MMseqs2 v 13.45111): mmseqs easy-cluster ${rep_input_fasta} ${output_prefix} tmp --dbtype 1 --cov-mode 0 -c 0.8 --min-seq-id 0.9   HMMer quieries (hmmer v 3.1b2, http://hmmer.org/download.html): hmmsearch --domtblout ${output_domtblout} --noali --cpu 15 ${derep_input_fasta} ${derep_input_fasta} &&gt; ${log_file}"   HMM-HMM comparisons (hh-suite 3.3.0): hhblits -i ${query_hmm} -d ${path_to_merged_databases_hhsuite} -o ${output_domtblout_hhr} -blasttab ${output_domtblout_btb} Network visualisations were created using Cytoscape 3.9.1 Other analyses were conducted using scripts submitted to: https://github.com/zwmuam/lysin_vocabulary
description: This dataset is from the paper: "Tear down that wall - updating the
 vocabulary of phage and bacterial lytic proteins" === Authors: Sophia
 Baldysz, Jakub Barylski, Robert Nawrot Contact e-mail address:
 jakub.barylski@amu.edu.pl. Reference Information === Provenance for this
 README --- * File name: README\_TearWall.txt * Author: Jakub Barylski *
 Other contributors: Sophia Baldysz * Date created: 2023-10-17 Contact
 Information --- * Name: Jakub Barylski * Affiliations: Department of
 Molecular Virology * ``` Institute of Experimental Biology ``` * ```
 Faculty of Biology ``` * ``` Adam Mickiewicz University in Poznan ``` *
 ``` Collegium Biologicum - ul. Uniwersytetu Poznańskiego 6 ``` * ```
 61-614 Poznan, Poland ``` * ORCID ID:
 https://orcid.org/0000-0001-6630-6932 * Email: jakub.barylski@amu.edu.pl *
 Name: Sophia Baldysz * Affiliations: Department of Molecular Virology *
 ``` Institute of Experimental Biology ``` * ``` Faculty of Biology ``` *
 ``` Adam Mickiewicz University in Poznan ``` * ``` Collegium Biologicum -
 ul. Uniwersytetu Poznańskiego 6 ``` * ``` 61-614 Poznan, Poland ``` *
 ORCID ID: https://orcid.org/0000-0001-9968-3929 * Email: sopbal@amu.edu.pl
 Dataset Attribution and Usage --- * Dataset Title: "Endolysin-related
 HMMs" * Persistent Identifier:
 https://doi.org/10.5061/dryad.fbg79cnsp * Source code:
 https://github.com/zwmuam/lysin\_vocabulary Methodological Information ===
 We selected a comprehensive set of lysin-related sequences, domains and
 families. First, we compiled de-replicated set of bona-fide lysins from
 Enzybase ("Lysin90.NonGM\_EnzyBase.fasta") Then conducted a
 HMMER search ("hmmsearch\_results") against the Enzybase
 database and the "background" set of bacterial and phage
 UniRef90 proteins
 ("UniRef90pb.Caudoviricetes\_2731619\_Bacteria\_2\_unclassified\_dsDNA\_phages\_79205\_UniProt.faa"). Based on this search we selected HMMs overrepresented in the lysin set. Finally we compared them to the complete model database visualised as "cytoscape\_networks" based on: 1. co-location ("hmmsearch\_results" analysed through Cytoscape\_table\_from\_colocation\_analysis.py), 2. direct HMM-HMM similarity ("hhblits\_results" analysed through Cytoscape\_table\_from\_hhblits.py). External data --- Input data were retrieved from: Sequences: http://biotechlab.fudan.edu.cn/database/EnzyBase https://www.uniprot.org Family/Domain databases: http://eggnog5.embl.de (ver. 5.0) http://pfam.xfam.org (ver. 33.0) http://dmk-brain.ecn.uiowa.edu/pVOGs (accessed 01.02.2020) https://vogdb.org (ver. vog99) Bioinformatic analysis --- Protein clustering (de-replication, MMseqs2 v 13.45111): mmseqs easy-cluster ${rep\_input\_fasta} ${output\_prefix} tmp --dbtype 1 --cov-mode 0 -c 0.8 --min-seq-id 0.9 HMMer quieries (hmmer v 3.1b2, http://hmmer.org/download.html): hmmsearch --domtblout ${output\_domtblout} --noali --cpu 15 ${derep\_input\_fasta} ${derep\_input\_fasta} &&gt; ${log\_file}" HMM-HMM comparisons (hh-suite 3.3.0): hhblits -i ${query\_hmm} -d ${path\_to\_merged\_databases\_hhsuite} -o ${output\_domtblout\_hhr} -blasttab ${output\_domtblout\_btb} Network visualisations were created using Cytoscape 3.9.1 Other analyses were conducted using scripts submitted to: https://github.com/zwmuam/lysin\_vocabulary The file included files were the basis of the HMM analysis performed in the paper. File types --- * fasta/faa - standard protein fasta sequence format * domtblout - tabular files generated by hmmscan/hmmsearch with "--domtblout" flag * ffdata/ffindex - hhsuite database files * hhr/btb - "hhblits default"/"tabular BLAST" format of hhblits HMM-HMM comparison (one HMM against a whole databse) * cys Cytoscape networks Data Structure === [193G] lysin\_vocabulary.HMM\_analysis\_v2 ├── [1.8M] cytoscape\_networks # cytoscape importable HMM-HMM similarity networks │ ├── [984K] Colocation\_analysis.cys │ └── [825K] HMM2HMM\_hhblits.cys ├── [ 26M] hhblits\_results # raw HMM-HMM comparisions │ ├── [147K] begg\_2ZCQV.btb │ ├── [272K] begg\_2ZCQV.hhr │ ├── [338K] begg\_306IT.btb │ ├── [247K] begg\_306IT.hhr │ ├── [164K] begg\_309RS.btb │ ├── [219K] begg\_309RS.hhr │ ├── [141K] begg\_30IKH.btb │ ├── [275K] begg\_30IKH.hhr │ ├── [ 24K] begg\_30PT3.btb │ ├── [ 26K] begg\_30PT3.hhr │ ├── [317K] begg\_31TVC.btb │ ├── [151K] begg\_31TVC.hhr │ ├── [327K] begg\_32E28.btb │ ├── [225K] begg\_32E28.hhr │ ├── [ 25K] begg\_32F1I.btb │ ├── [113K] begg\_32F1I.hhr │ ├── [154K] begg\_32G2Z.btb │ ├── [145K] begg\_32G2Z.hhr │ ├── [ 18K] begg\_32R25.btb │ ├── [ 74K] begg\_32R25.hhr │ ├── [114K] begg\_32YYR.btb │ ├── [267K] begg\_32YYR.hhr │ ├── [978K] begg\_338B2.btb │ ├── [352K] begg\_338B2.hhr │ ├── [ 14K] begg\_33Q34.btb │ ├── [ 27K] begg\_33Q34.hhr │ ├── [ 12K] begg\_346W6.btb │ ├── [ 12K] begg\_346W6.hhr │ ├── [890K] begg\_34AXW.btb │ ├── [296K] begg\_34AXW.hhr │ ├── [109K] begg\_COG0739.btb │ ├── [ 48K] begg\_COG0739.hhr │ ├── [ 84K] begg\_COG0791.btb │ ├── [171K] begg\_COG0791.hhr │ ├── [134K] begg\_COG0860.btb │ ├── [ 14K] begg\_COG0860.hhr │ ├── [382K] begg\_COG1652.btb │ ├── [438K] begg\_COG1652.hhr │ ├── [430K] begg\_COG1705.btb │ ├── [102K] begg\_COG1705.hhr │ ├── [119K] begg\_COG1876.btb │ ├── [ 57K] begg\_COG1876.hhr │ ├── [127K] begg\_COG2989.btb │ ├── [ 67K] begg\_COG2989.hhr │ ├── [ 32K] begg\_COG3409.btb │ ├── [ 34K] begg\_COG3409.hhr │ ├── [ 36K] begg\_COG3757.btb │ ├── [ 29K] begg\_COG3757.hhr │ ├── [ 83K] begg\_COG3772.btb │ ├── [ 31K] begg\_COG3772.hhr │ ├── [271K] begg\_COG3807.btb │ ├── [495K] begg\_COG3807.hhr │ ├── [ 24K] begg\_COG3942.btb │ ├── [ 49K] begg\_COG3942.hhr │ ├── [227K] begg\_COG4193.btb │ ├── [ 38K] begg\_COG4193.hhr │ ├── [ 92K] begg\_COG5263.btb │ ├── [ 66K] begg\_COG5263.hhr │ ├── [ 43K] begg\_COG5632.btb │ ├── [ 15K] begg\_COG5632.hhr │ ├── [ 12K] PFAM\_\_Amidase02\_C.btb │ ├── [ 35K] PFAM\_\_Amidase02\_C.hhr │ ├── [ 10K] PFAM\_\_Amidase\_2.btb │ ├── [ 32K] PFAM\_\_Amidase\_2.hhr │ ├── [7.5K] PFAM\_\_Amidase\_3.btb │ ├── [ 21K] PFAM\_\_Amidase\_3.hhr │ ├── [ 26K] PFAM\_\_Amidase\_5.btb │ ├── [104K] PFAM\_\_Amidase\_5.hhr │ ├── [ 14K] PFAM\_\_CHAP.btb │ ├── [ 73K] PFAM\_\_CHAP.hhr │ ├── [ 11K] PFAM\_\_CW\_7.btb │ ├── [ 36K] PFAM\_\_CW\_7.hhr │ ├── [ 10K] PFAM\_\_CW\_binding\_1.btb │ ├── [ 53K] PFAM\_\_CW\_binding\_1.hhr │ ├── [137K] PFAM\_\_DUF3597.btb │ ├── [ 44K] PFAM\_\_DUF3597.hhr │ ├── [8.1K] PFAM\_\_G5.btb │ ├── [9.5K] PFAM\_\_G5.hhr │ ├── [8.6K] PFAM\_\_Glucosaminidase.btb │ ├── [ 42K] PFAM\_\_Glucosaminidase.hhr │ ├── [7.2K] PFAM\_\_Glyco\_hydro\_25.btb │ ├── [ 12K] PFAM\_\_Glyco\_hydro\_25.hhr │ ├── [ 11K] PFAM\_\_GW.btb │ ├── [ 41K] PFAM\_\_GW.hhr │ ├── [ 23K] PFAM\_\_Lys.btb │ ├── [ 46K] PFAM\_\_Lys.hhr │ ├── [ 13K] PFAM\_\_LysM.btb │ ├── [ 98K] PFAM\_\_LysM.hhr │ ├── [8.6K] PFAM\_\_Peptidase\_M15\_4.btb │ ├── [ 34K] PFAM\_\_Peptidase\_M15\_4.hhr │ ├── [9.8K] PFAM\_\_Peptidase\_M23.btb │ ├── [ 78K] PFAM\_\_Peptidase\_M23.hhr │ ├── [ 15K] PFAM\_\_PG\_binding\_1.btb │ ├── [ 90K] PFAM\_\_PG\_binding\_1.hhr │ ├── [ 11K] PFAM\_\_Phage\_lysozyme.btb │ ├── [ 32K] PFAM\_\_Phage\_lysozyme.hhr │ ├── [ 19K] PFAM\_\_Prophage\_tail.btb │ ├── [156K] PFAM\_\_Prophage\_tail.hhr │ ├── [9.2K] PFAM\_\_PSA\_CBD.btb │ ├── [ 12K] PFAM\_\_PSA\_CBD.hhr │ ├── [ 29K] PFAM\_\_SH3\_3.btb │ ├── [233K] PFAM\_\_SH3\_3.hhr │ ├── [ 12K] PFAM\_\_SH3\_5.btb │ ├── [ 35K] PFAM\_\_SH3\_5.hhr │ ├── [9.5K] PFAM\_\_SLH.btb │ ├── [ 54K] PFAM\_\_SLH.hhr │ ├── [9.3K] PFAM\_\_VanY.btb │ ├── [ 36K] PFAM\_\_VanY.hhr │ ├── [7.1K] PFAM\_\_ZoocinA\_TRD.btb │ ├── [9.2K] PFAM\_\_ZoocinA\_TRD.hhr │ ├── [ 23K] pVOGS\_VOG0352.btb │ ├── [ 58K] pVOGS\_VOG0352.hhr │ ├── [ 45K] pVOGS\_VOG10230.btb │ ├── [ 82K] pVOGS\_VOG10230.hhr │ ├── [ 20K] pVOGS\_VOG11038.btb │ ├── [103K] pVOGS\_VOG11038.hhr │ ├── [417K] pVOGS\_VOG3721.btb │ ├── [125K] pVOGS\_VOG3721.hhr │ ├── [ 33K] pVOGS\_VOG4565.btb │ ├── [ 51K] pVOGS\_VOG4565.hhr │ ├── [ 25K] pVOGS\_VOG4574.btb │ ├── [ 18K] pVOGS\_VOG4574.hhr │ ├── [359K] pVOGS\_VOG4599.btb │ ├── [315K] pVOGS\_VOG4599.hhr │ ├── [656K] pVOGS\_VOG4615.btb │ ├── [328K] pVOGS\_VOG4615.hhr │ ├── [ 23K] pVOGS\_VOG4649.btb │ ├── [100K] pVOGS\_VOG4649.hhr │ ├── [ 49K] pVOGS\_VOG4666.btb │ ├── [ 95K] pVOGS\_VOG4666.hhr │ ├── [ 21K] pVOGS\_VOG4707.btb │ ├── [ 26K] pVOGS\_VOG4707.hhr │ ├── [153K] pVOGS\_VOG4724.btb │ ├── [ 42K] pVOGS\_VOG4724.hhr │ ├── [ 19K] pVOGS\_VOG4772.btb │ ├── [ 48K] pVOGS\_VOG4772.hhr │ ├── [ 22K] pVOGS\_VOG4824.btb │ ├── [102K] pVOGS\_VOG4824.hhr │ ├── [ 38K] pVOGS\_VOG4865.btb │ ├── [120K] pVOGS\_VOG4865.hhr │ ├── [ 34K] pVOGS\_VOG4910.btb │ ├── [ 79K] pVOGS\_VOG4910.hhr │ ├── [ 65K] pVOGS\_VOG4918.btb │ ├── [272K] pVOGS\_VOG4918.hhr │ ├── [ 20K] pVOGS\_VOG4941.btb │ ├── [ 39K] pVOGS\_VOG4941.hhr │ ├── [ 95K] pVOGS\_VOG4985.btb │ ├── [193K] pVOGS\_VOG4985.hhr │ ├── [174K] pVOGS\_VOG6576.btb │ ├── [ 96K] pVOGS\_VOG6576.hhr │ ├── [ 16K] pVOGS\_VOG7635.btb │ ├── [ 53K] pVOGS\_VOG7635.hhr │ ├── [ 37K] pVOGS\_VOG8236.btb │ ├── [136K] pVOGS\_VOG8236.hhr │ ├── [ 14K] pVOGS\_VOG8294.btb │ ├── [ 31K] pVOGS\_VOG8294.hhr │ ├── [ 57K] pVOGS\_VOG9502.btb │ ├── [162K] pVOGS\_VOG9502.hhr │ ├── [143K] vegg\_4QAVB.btb │ ├── [112K] vegg\_4QAVB.hhr │ ├── [ 38K] vegg\_4QAZY.btb │ ├── [ 71K] vegg\_4QAZY.hhr │ ├── [ 47K] vegg\_4QB01.btb │ ├── [192K] vegg\_4QB01.hhr │ ├── [110K] vegg\_4QBQV.btb │ ├── [198K] vegg\_4QBQV.hhr │ ├── [ 38K] vegg\_4QCGD.btb │ ├── [125K] vegg\_4QCGD.hhr │ ├── [ 36K] vegg\_4QECV.btb │ ├── [ 82K] vegg\_4QECV.hhr │ ├── [ 35K] vegg\_4QENP.btb │ ├── [126K] vegg\_4QENP.hhr │ ├── [ 38K] vegg\_4QEUP.btb │ ├── [ 73K] vegg\_4QEUP.hhr │ ├── [288K] vog2017\_VOG00190.btb │ ├── [299K] vog2017\_VOG00190.hhr │ ├── [ 55K] vog2017\_VOG00298.btb │ ├── [222K] vog2017\_VOG00298.hhr │ ├── [190K] vog2017\_VOG00438.btb │ ├── [101K] vog2017\_VOG00438.hhr │ ├── [123K] vog2017\_VOG00798.btb │ ├── [168K] vog2017\_VOG00798.hhr │ ├── [ 71K] vog2017\_VOG00953.btb │ ├── [149K] vog2017\_VOG00953.hhr │ ├── [421K] vog2017\_VOG01046.btb │ ├── [269K] vog2017\_VOG01046.hhr │ ├── [ 28K] vog2017\_VOG01142.btb │ ├── [ 36K] vog2017\_VOG01142.hhr │ ├── [ 16K] vog2017\_VOG01143.btb │ ├── [ 33K] vog2017\_VOG01143.hhr │ ├── [ 57K] vog2017\_VOG01370.btb │ ├── [ 60K] vog2017\_VOG01370.hhr │ ├── [ 40K] vog2017\_VOG01885.btb │ ├── [132K] vog2017\_VOG01885.hhr │ ├── [229K] vog2017\_VOG02043.btb │ ├── [ 70K] vog2017\_VOG02043.hhr │ ├── [ 80K] vog2017\_VOG02530.btb │ ├── [215K] vog2017\_VOG02530.hhr │ ├── [ 30K] vog2017\_VOG03024.btb │ ├── [ 90K] vog2017\_VOG03024.hhr │ ├── [ 45K] vog2017\_VOG03088.btb │ ├── [ 84K] vog2017\_VOG03088.hhr │ ├── [586K] vog2017\_VOG03420.btb │ ├── [240K] vog2017\_VOG03420.hhr │ ├── [337K] vog2017\_VOG04785.btb │ ├── [102K] vog2017\_VOG04785.hhr │ ├── [ 72K] vog2017\_VOG09725.btb │ ├── [264K] vog2017\_VOG09725.hhr │ ├── [390K] vog2017\_VOG09928.btb │ ├── [124K] vog2017\_VOG09928.hhr │ ├── [ 65K] vog2017\_VOG11215.btb │ ├── [212K] vog2017\_VOG11215.hhr │ ├── [206K] vog2017\_VOG11220.btb │ ├── [ 65K] vog2017\_VOG11220.hhr │ ├── [ 14K] vog2017\_VOG11377.btb │ ├── [ 44K] vog2017\_VOG11377.hhr │ ├── [ 50K] vog2017\_VOG12191.btb │ ├── [ 53K] vog2017\_VOG12191.hhr │ ├── [ 39K] vog2017\_VOG18536.btb │ ├── [ 43K] vog2017\_VOG18536.hhr │ ├── [ 88K] vog2017\_VOG18969.btb │ ├── [ 59K] vog2017\_VOG18969.hhr │ ├── [ 14K] vog2017\_VOG21001.btb │ ├── [ 31K] vog2017\_VOG21001.hhr │ ├── [ 93K] vog2017\_VOG21772.btb │ ├── [106K] vog2017\_VOG21772.hhr │ ├── [ 22K] vog2017\_VOG22320.btb │ ├── [ 52K] vog2017\_VOG22320.hhr │ ├── [ 32K] vog2017\_VOG23062.btb │ ├── [ 84K] vog2017\_VOG23062.hhr │ ├── [ 66K] vog2017\_VOG23388.btb │ ├── [157K] vog2017\_VOG23388.hhr │ ├── [ 97K] vog2017\_VOG23635.btb │ ├── [297K] vog2017\_VOG23635.hhr │ ├── [ 89K] vog2017\_VOG24666.btb │ └── [ 52K] vog2017\_VOG24666.hhr ├── [128G] hmmsearch\_results # results of HMMer3 search │ ├── [515K] Lysin90.AllvogHMMprofiles.domtblout │ ├── [3.5M] Lysin90.bacterialHMMdbupdated.domtblout │ ├── [519K] Lysin90.Pfam-A.domtblout │ ├── [179K] Lysin90.viralHMMdb.domtblout │ ├── [883K] Lysin90.vog2017db.domtblout │ ├── [3.7G] UniRef90pb.AllvogHMMprofiles.hmm.domtblout │ ├── [ 97G] UniRef90pb.bacterialHMMdbupdated.hmm.domtblout │ ├── [ 18G] UniRef90pb.Pfam-A.hmm.domtblout │ ├── [2.5G] UniRef90pb.viralHMMdb.hmm.domtblout │ └── [7.3G] UniRef90pb.vog2017db.hmm.domtblout ├── [ 46G] merged\_databases\_hhsuite # master HH-suite3 database files │ ├── [ 10G] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_a3m.ffdata │ ├── [7.3M] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_a3m.ffindex │ ├── [ 56M] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_cs219.ffdata │ ├── [6.3M] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_cs219.ffindex │ ├── [5.5G] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_hhm.ffdata │ ├── [7.3M] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_hhm.ffindex │ ├── [ 31G] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_msa.ffdata │ └── [7.2M] AllvogHMMprofiles\_\_bacterialHMMdbupdated\_\_Pfam-A\_\_viralHMMdb\_\_vog2017db\_msa.ffindex ├── [190K] Lysin90.NonGM\_EnzyBase.fasta # "positive" endolysin sequence dataset ├── [189K] Negative.NonLysin\_UniRef90pb.fasta # "negative" NON-endolysin sequence dataset used for testing and debugging purposes └── [5.3G] UniRef90pb.Caudoviricetes\_2731619\_Bacteria\_2\_unclassified\_dsDNA\_phages\_79205\_UniProt.faa # "background" bacterial/phage protein dataset