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Toxins
Special Issues
Omics Approaches to Study Toxins
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Omics Approaches to Study Toxins

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: closed (25 June 2023) | Viewed by 9999

Special Issue Editor

Dr. Joseph D. Romano

E-Mail Website
Guest Editor
Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA
Interests: translational bioinformatics; computational toxicology; natural product drug discovery; artificial intelligence; systems biology; systems pharmacology; knowledge representation; venomics

Special Issue Information

Dear Colleagues,

In the era of systems biology and biomedical big data, new developments in multi-omics technologies allow researchers to study living systems in ways that are not possible by investigating single biomolecules in isolation. Broadly, ‘omics approaches’ refers to the simultaneous characterization of large collections of co-occurring biomolecules, including genes (genomics), proteins (proteomics), messenger RNA (transcriptomics), metabolites (metabolomics), and others. Emerging trends in omics-based research have spread to many diverse disciplines, and the study of toxins is no exception. Over the past several decades, omics approaches have been used to profile the biochemical makeup of crude toxins, understand the genetic/metabolic mechanisms that underlie toxin synthesis in vivo, and explain the evolutionary origins of toxins and the roles they play in ecosystems. Importantly, these omics methods can be applied to both toxins (e.g., venom gland proteomics) and the systems those toxins act upon (e.g., effects of toxins on differential gene expression).

In this Special Issue, we seek to assemble a broad collection of original research studies describing innovative omics-based approaches for quantifying and understanding toxins and the effects they have on living systems. We are particularly interested in highlighting novel methods for data collection and analysis, and applications that leverage multiple omics technologies.

Dr. Joseph D. Romano
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • genomics
  • proteomics
  • transcriptomics
  • metabolomics
  • bioinformatics
  • sequencing
  • toxin profiling
  • systems biology

Published Papers (6 papers)

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Editorial

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2 pages, 212 KiB  
Editorial
Omics Methods in Toxins Research—A Toolkit to Drive the Future of Scientific Inquiry
by Joseph D. Romano
Toxins 2022, 14(11), 761; https://doi.org/10.3390/toxins14110761 - 04 Nov 2022
Cited by 1 | Viewed by 1053
Abstract
A major trend in biomedical research has been an ideological shift away from studying individual components of an organism or biological process in isolation, and towards how those components function collectively, forming the basis of the field now known as systems biology [...] [...] Read more.
A major trend in biomedical research has been an ideological shift away from studying individual components of an organism or biological process in isolation, and towards how those components function collectively, forming the basis of the field now known as systems biology [...] Full article
(This article belongs to the Special Issue Omics Approaches to Study Toxins)

Research

Jump to: Editorial

33 pages, 4668 KiB  
Article
Discovering Venom-Derived Drug Candidates Using Differential Gene Expression
by Joseph D. Romano, Hai Li, Tanya Napolitano, Ronald Realubit, Charles Karan, Mandë Holford and Nicholas P. Tatonetti
Toxins 2023, 15(7), 451; https://doi.org/10.3390/toxins15070451 - 09 Jul 2023
Viewed by 1279
Abstract
Venoms are a diverse and complex group of natural toxins that have been adapted to treat many types of human disease, but rigorous computational approaches for discovering new therapeutic activities are scarce. We have designed and validated a new platform—named VenomSeq—to systematically identify [...] Read more.
Venoms are a diverse and complex group of natural toxins that have been adapted to treat many types of human disease, but rigorous computational approaches for discovering new therapeutic activities are scarce. We have designed and validated a new platform—named VenomSeq—to systematically identify putative associations between venoms and drugs/diseases via high-throughput transcriptomics and perturbational differential gene expression analysis. In this study, we describe the architecture of VenomSeq and its evaluation using the crude venoms from 25 diverse animal species and 9 purified teretoxin peptides. By integrating comparisons to public repositories of differential expression, associations between regulatory networks and disease, and existing knowledge of venom activity, we provide a number of new therapeutic hypotheses linking venoms to human diseases supported by multiple layers of preliminary evidence. Full article
(This article belongs to the Special Issue Omics Approaches to Study Toxins)
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18 pages, 3086 KiB  
Article
Venom Proteomics of Trimeresurus gracilis, a Taiwan-Endemic Pitviper, and Comparison of Its Venom Proteome and VEGF and CRISP Sequences with Those of the Most Related Species
by Tsz-Chun Tse, Inn-Ho Tsai, Yuen-Ying Chan and Tein-Shun Tsai
Toxins 2023, 15(7), 408; https://doi.org/10.3390/toxins15070408 - 22 Jun 2023
Cited by 2 | Viewed by 1513
Abstract
Trimeresurus gracilis is an endemic alpine pitviper in Taiwan with controversial phylogeny, and its venom proteome remains unknown. In this study, we conducted a proteomic analysis of T. gracilis venom using high-performance liquid chromatography-tandem mass spectrometry and identified 155 toxin proteoforms that belong to [...] Read more.
Trimeresurus gracilis is an endemic alpine pitviper in Taiwan with controversial phylogeny, and its venom proteome remains unknown. In this study, we conducted a proteomic analysis of T. gracilis venom using high-performance liquid chromatography-tandem mass spectrometry and identified 155 toxin proteoforms that belong to 13 viperid venom toxin families. By searching the sequences of trypsin-digested peptides of the separated HPLC fractions against the NCBI database, T. gracilis venom was found to contain 40.3% metalloproteases (SVMPs), 15.3% serine proteases, 6.6% phospholipases A2, 5.0% L-amino acid oxidase, 4.6% Cys-rich secretory proteins (CRISPs), 3.2% disintegrins, 2.9% vascular endothelial growth factors (VEGFs), 1.9% C-type lectin-like proteins, and 20.2% of minor toxins, nontoxins, and unidentified peptides or compounds. Sixteen of these proteoforms matched the toxins whose full amino-acid sequences have been deduced from T. gracilis venom gland cDNA sequences. The hemorrhagic venom of T. gracilis appears to be especially rich in PI-class SVMPs and lacks basic phospholipase A2. We also cloned and sequenced the cDNAs encoding two CRISP and three VEGF variants from T. gracilis venom glands. Sequence alignments and comparison revealed that the PI-SVMP, kallikrein-like proteases, CRISPs, and VEGF-F of T. gracilis and Ovophis okinavensis are structurally most similar, consistent with their close phylogenetic relationship. However, the expression levels of some of their toxins were rather different, possibly due to their distinct ecological and prey conditions. Full article
(This article belongs to the Special Issue Omics Approaches to Study Toxins)
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15 pages, 10298 KiB  
Article
Zearalenone Exposure Disrupts STAT-ISG15 in Rat Colon: A Potential Linkage between Zearalenone and Inflammatory Bowel Disease
by Haonan Ruan, Jiashuo Wu, Fangqing Zhang, Ziyue Jin, Jiao Tian, Jing Xia, Jiaoyang Luo and Meihua Yang
Toxins 2023, 15(6), 392; https://doi.org/10.3390/toxins15060392 - 09 Jun 2023
Viewed by 1394
Abstract
Zearalenone (ZEN), a prevalent mycotoxin contaminating food and known for its intestinal toxicity, has been suggested as a potential risk factor for inflammatory bowel disease (IBD), although the exact relationship between ZEN exposure and IBD remains unclear. In this study, we established a [...] Read more.
Zearalenone (ZEN), a prevalent mycotoxin contaminating food and known for its intestinal toxicity, has been suggested as a potential risk factor for inflammatory bowel disease (IBD), although the exact relationship between ZEN exposure and IBD remains unclear. In this study, we established a rat model of colon toxicity induced by ZEN exposure to investigate the key targets of ZEN-induced colon toxicity and explore the underlying connection between ZEN exposure and IBD. Histological staining of the rat colon revealed significant pathological changes resulting from ZEN exposure (p < 0.01). Furthermore, the proteomic analysis demonstrated a notable upregulation of protein expression levels, specifically STAT2 (0.12 ± 0.0186), STAT6 (0.36 ± 0.0475) and ISG15 (0.43 ± 0.0226) in the rat colon (p < 0.05). Utilizing bioinformatics analysis, we combined ZEN exposure and IBD clinical sample databases to reveal that ZEN exposure may increase the risk of IBD through activation of the STAT-ISG15 pathway. This study identified novel targets for ZEN-induced intestinal toxicity, providing the basis for further study of ZEN exposure to IBD. Full article
(This article belongs to the Special Issue Omics Approaches to Study Toxins)
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15 pages, 1860 KiB  
Article
Next-Generation Sequencing for Venomics: Application of Multi-Enzymatic Limited Digestion for Inventorying the Snake Venom Arsenal
by Fernanda Gobbi Amorim, Damien Redureau, Thomas Crasset, Lou Freuville, Dominique Baiwir, Gabriel Mazzucchelli, Stefanie K. Menzies, Nicholas R. Casewell and Loïc Quinton
Toxins 2023, 15(6), 357; https://doi.org/10.3390/toxins15060357 - 25 May 2023
Cited by 4 | Viewed by 1982
Abstract
To improve the characterization of snake venom protein profiles, we report the application of a new generation of proteomic methodology to deeply characterize complex protein mixtures. The new approach, combining a synergic multi-enzymatic and a time-limited digestion (MELD), is a versatile and straightforward [...] Read more.
To improve the characterization of snake venom protein profiles, we report the application of a new generation of proteomic methodology to deeply characterize complex protein mixtures. The new approach, combining a synergic multi-enzymatic and a time-limited digestion (MELD), is a versatile and straightforward protocol previously developed by our group. The higher number of overlapping peptides generated during MELD increases the quality of downstream peptide sequencing and of protein identification. In this context, this work aims at applying the MELD strategy to a venomics purpose for the first time, and especially for the characterization of snake venoms. We used four venoms as the test models for this proof of concept: two Elapidae (Dendroaspis polylepis and Naja naja) and two Viperidae (Bitis arietans and Echis ocellatus). Each venom was reduced and alkylated before being submitted to two different protocols: the classical bottom-up proteomics strategy including a digestion step with trypsin only, or MELD, which combines the activities of trypsin, Glu-C and chymotrypsin with a limited digestion approach. The resulting samples were then injected on an M-Class chromatographic system, and hyphenated to a Q-Exactive Mass Spectrometer. Toxins and protein identification were performed by Peaks Studio X+. The results show that MELD considerably improves the number of sequenced (de novo) peptides and identified peptides from protein databases, leading to the unambiguous identification of a greater number of toxins and proteins. For each venom, MELD was successful, not only in terms of the identification of the major toxins (increasing of sequence coverage), but also concerning the less abundant cellular components (identification of new groups of proteins). In light of these results, MELD represents a credible methodology to be applied as the next generation of proteomics approaches dedicated to venomic analysis. It may open new perspectives for the sequencing and inventorying of the venom arsenal and should expand global knowledge about venom composition. Full article
(This article belongs to the Special Issue Omics Approaches to Study Toxins)
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22 pages, 3242 KiB  
Article
Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells
by Éva Márton, Alexandra Varga, András Penyige, Zsuzsanna Birkó, István Balogh, Bálint Nagy and Melinda Szilágyi
Toxins 2023, 15(2), 140; https://doi.org/10.3390/toxins15020140 - 09 Feb 2023
Viewed by 1730
Abstract
Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in [...] Read more.
Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in the PEO1 human ovarian cell line by mRNA and microRNA sequencing. Estrogen exposure induced remarkable transcriptomic changes: 308, 288 and 63 genes were upregulated (log2FC > 1); 292, 260 and 45 genes were downregulated (log2FC < −1) in response to E2 (10 nM), ZEA (10 nM) and BPA (100 nM), respectively. Furthermore, the expression of 13, 11 and 10 miRNAs changed significantly (log2FC > 1, or log2FC < −1) after exposure to E2, ZEA and BPA, respectively. Functional enrichment analysis of the significantly differentially expressed genes and miRNAs revealed several pathways related to the regulation of cell proliferation and migration. The effect of E2 and ZEA was highly comparable: 407 genes were coregulated by these molecules. We could identify 83 genes that were regulated by all three treatments that might have a significant role in the estrogen response of ovarian cells. Furthermore, the downregulation of several miRNAs (miR-501-5p, let-7a-2-3p, miR-26a-2-3p, miR-197-5p and miR-582-3p) was confirmed by qPCR, which might support the proliferative effect of estrogens in ovarian cells. Full article
(This article belongs to the Special Issue Omics Approaches to Study Toxins)
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