ToxCodAn: a new toxin annotator and guide to venom gland transcriptomics

Nachtigall, Pedro Gabriel; Rautsaw, Rhett M.; Ellsworth, Schyler A.; Mason, Andrew J.; Rokyta, Darin R.; Parkinson, Christopher L.; Junqueira-de-Azevedo, Inácio L.M.

doi:10.1093/bib/bbab095

Cited by 13 publications

(8 citation statements)

References 51 publications

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“…Toxins are encoded by relatively short coding sequences (CDSs), and while animal genomes typically contain no more than 40–50 000 ORFs, transcriptomes predict far more ORFs, making it challenging to distinguish real ORFs from bioinformatics artifacts. Existing tools like Conodictor 2 [ 14 ], Venomix [ 23 ] or ToxCodAn [ 22 ] are unsuitable for handling large data sets, face issues with maintenance and software compatibility, and lack integration across all steps, from assembly to toxin identification, requiring manual execution of multiple programs. For instance, Venomix necessitates three input files, including alignment against a toxin database, an assembled transcriptome and a gene expression quantification file, complicating the process.…”

Section: Discussionmentioning

confidence: 99%

DeTox: a pipeline for the detection of toxins in venomous organisms

Ringeval,

Farhat,

Fedosov

et al. 2024

Briefings in Bioinformatics

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Venomous organisms have independently evolved the ability to produce toxins 101 times during their evolutionary history, resulting in over 200 000 venomous species. Collectively, these species produce millions of toxins, making them a valuable resource for bioprospecting and understanding the evolutionary mechanisms underlying genetic diversification. RNA-seq is the preferred method for characterizing toxin repertoires, but the analysis of the resulting data remains challenging. While early approaches relied on similarity-based mapping to known toxin databases, recent studies have highlighted the importance of structural features for toxin detection. The few existing pipelines lack an integration between these complementary approaches, and tend to be difficult to run for non-experienced users. To address these issues, we developed DeTox, a comprehensive and user-friendly tool for toxin research. It combines fast execution, parallelization and customization of parameters. DeTox was tested on published transcriptomes from gastropod mollusks, cnidarians and snakes, retrieving most putative toxins from the original articles and identifying additional peptides as potential toxins to be confirmed through manual annotation and eventually proteomic analysis. By integrating a structure-based search with similarity-based approaches, DeTox allows the comprehensive characterization of toxin repertoire in poorly-known taxa. The effect of the taxonomic bias in existing databases is minimized in DeTox, as mirrored in the detection of unique and divergent toxins that would have been overlooked by similarity-based methods. DeTox streamlines toxin annotation, providing a valuable tool for efficient identification of venom components that will enhance venom research in neglected taxa.

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Section: Discussionmentioning

confidence: 99%

DeTox: a pipeline for the detection of toxins in venomous organisms

Ringeval,

Farhat,

Fedosov

et al. 2024

Briefings in Bioinformatics

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“…De novo assemblies for each B. arietans venom gland transcriptome were merged, and redundancy and contigs less than 150 bp were removed with CD-HIT (v4.8.1) (42,43). Toxins were then annotated using ToxCodAn (44) and Diamond (v2.0.11) (45) BLASTx (E-value 10 -05 cut-off) searches against the National Center for Biotechnology Information (NCBI) non-redundant protein database (accessed February 2023). Toxin transcripts were manually checked to determine that all translations were non-redundant, full-length proteins (methionine start codon to stop codon), had a maximum of three ambiguous amino acid residues, shared sequence identity with currently known toxins, and contained a conserved signal peptide sequence within each venom protein family.…”

Section: Methodsmentioning

confidence: 99%

Intraspecific venom variation in the medically important puff adder (Bitis arietans): comparative venom gland transcriptomics, in vitro venom activity and immunological recognition by antivenom

Dawson,

Bartlett,

Wilkinson

et al. 2024

Preprint

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BackgroundVariation in snake venoms is well documented, both between and within species, with intraspecific venom variation often correlated with geographically distinct populations. The puff adder,Bitis arietans, is found widely distributed across sub-Saharan Africa and into the Arabian Peninsula where it is considered a leading cause of the ∼310,000 annual snakebites across the region, with its venom capable of causing substantial morbidity and mortality. Despite its medical importance and wide geographic distribution, there is little known about venom variation between differentB. arietanspopulations and the potential implications of this variation on antivenom efficacy.MethodologyWe applied a range of analyses, including venom gland transcriptomics,in vitroenzymatic assays and reverse phase chromatography to comparatively analyseB. arietansvenoms originating from Nigeria, Tanzania, and South Africa. Immunological assays andin vitroenzymatic neutralisation assays were then applied to investigate the impact of venom variation on the potential efficacy of three antivenom products; SAIMR Polyvalent, EchiTAb-Plus and Fav-Afrique.FindingsThrough the first comparison of venom gland transcriptomes ofB. arietansfrom three geographically distinct regions (Nigeria, Tanzania, and South Africa), we identified substantial variation in toxin expression. Findings of venom variation were further supported by chromatographic venom profiling, and the application of enzymatic assays to quantify the activity of three pathologically relevant toxin families. However, the use of western blotting, ELISA, andin vitroenzymatic inhibition assays revealed that variation withinB. arietansvenom does not appear to substantially impact upon the efficacy of three African polyvalent antivenoms.ConclusionsThe large distribution and medical importance ofB. arietansmakes this species ideal for understanding venom variation and the impact this has on therapeutic efficacy. The findings in this study highlight the likelihood for considerable venom toxin variation across the range ofB. arietans,but that this may not dramatically impact upon the utility of treatment available in the region.Author SummaryThe puff adder (Bitis arietans) is found across sub-Saharan Africa and the Arabian Peninsula and is capable of causing life threatening pathology due to its potent venom. The extensive range ofB. arietansexposes populations to different ecological pressures which may impact upon the composition of venom toxins. In this study, we examined the venom composition ofB. arietansfrom three countries separated by large geographic distance: Nigeria, Tanzanian and South Africa. By integrating venom gland transcriptomes, venom chromatography, andin vitrofunctional assays to profileB. arietansvenom composition, we uncovered extensive variation between the three locales. Given that venom variation can have a significant impact on the efficacy of antivenom treatment, we also investigated the ability of three African antivenoms to recognise and inhibitin vitrovenom activity. Through these analyses, we were able to determine that venom variation did not have a substantial impact on the neutralising effect of selected antivenoms. This study has highlighted the potentially extensive venom variation found across the range ofB. arietansand initiated valuable investigations into the efficacy of African antivenoms to protect human populations vulnerable to snakebite envenoming.

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“…We ran all the assemblies in a standardized way using five different assemblers with different k-mer values and assembly parameters (Trinity: k-mer 31; rnaSPADES: k-mer 31, 75, and 127; Extender: default, overlap 150, and seed size 2000; SeqMan Ngen: k-mer 21; and Bridger: k-mer 30) ( Grabherr et al 2011 ; Rokyta et al 2012 ; Chang et al 2015 ; Holding et al 2018 ; Bushmanova et al 2019 ). Then, we performed toxin annotation using ToxCodan ( Nachtigall, Rautsaw, et al 2021 ) against a curated data set of toxin sequences. Annotated toxin transcripts were manually reviewed and used to purge toxic-like contigs from the Trinity assembly of each individual.…”

Section: Methodsmentioning

confidence: 99%

Independent Recruitment of Different Types of Phospholipases A2 to the Venoms of Caenophidian Snakes: The Rise of PLA2-IIE within Pseudoboini (Dipsadidae)

Bayona-Serrano

Grazziotin

Salazar-Valenzuela

et al. 2023

Molecular Biology and Evolution

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Snake venom harbors a wide and diverse array of enzymatic and nonenzymatic toxic components, allowing them to exert myriad effects on their prey. However, they appear to trend toward a few optimal compositional scaffolds, dominated by four major toxin classes: SVMPs, SVSPs, 3FTxs and PLA2s. Nevertheless, the latter appears to be restricted to vipers and elapids, as it has never been reported as a major venom component in rear-fanged species. Here, by investigating the original transcriptomes from 19 species distributed in eight genera from the Pseudoboini tribe (Dipsadidae: Xenodontinae) and screening among seven additional tribes of Dipsadidae and three additional families of advanced snakes, we discovered that a novel type of venom, PLA2, resembling a PLA2-IIE, has been recruited to the venom of some species of the Pseudoboini tribe, where it is a major component. Proteomic and functional analyses of these venoms further indicate that these PLA2s play a relevant role in the venoms from this tribe. Moreover, we reconstructed the phylogeny of PLA2s across different snake groups and show that different types of these toxins have been recruited in at least five independent events in caenophidian snakes. Additionally, we present the first compositional profiling of Pseudoboini venoms. Our results demonstrate how relevant phenotypic traits are convergently recruited by different means and from homologous and nonhomologous genes in phylogenetically and ecologically divergent snake groups, possibly optimizing venom composition to overcome diverse adaptative landscapes.

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ToxCodAn: a new toxin annotator and guide to venom gland transcriptomics

Cited by 13 publications

References 51 publications

DeTox: a pipeline for the detection of toxins in venomous organisms

DeTox: a pipeline for the detection of toxins in venomous organisms

Intraspecific venom variation in the medically important puff adder (Bitis arietans): comparative venom gland transcriptomics, in vitro venom activity and immunological recognition by antivenom

Independent Recruitment of Different Types of Phospholipases A2 to the Venoms of Caenophidian Snakes: The Rise of PLA2-IIE within Pseudoboini (Dipsadidae)

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