Discovering Venom-Derived Drug Candidates Using Differential Gene Expression

Author:

Romano Joseph D.123ORCID,Li Hai45,Napolitano Tanya67,Realubit Ronald45,Karan Charles45,Holford Mandë678910ORCID,Tatonetti Nicholas P.11ORCID

Affiliation:

1. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA

2. Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA

3. Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA 19104, USA

4. Department of Systems Biology, Columbia University, New York, NY 10032, USA

5. Columbia Genome Center, Columbia University, New York, NY 10032, USA

6. Department of Chemistry, CUNY Hunter College, New York, NY 10032, USA

7. The PhD Program in Biochemistry, Graduate Center of the City University of New York, New York, NY 10016, USA

8. The PhD Program in Chemistry, Graduate Center of the City University of New York, New York, NY 10016, USA

9. The PhD Program in Biology, Graduate Center of the City University of New York, New York, NY 10016, USA

10. Department of Invertebrate Zoology, The American Museum of Natural History, New York, NY 10032, USA

11. Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA 90069, USA

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 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.

Funder

United States National Library of Medicine

National Institute of Environmental Health Sciences

National Cancer Institute

Publisher

MDPI AG

Subject

Health, Toxicology and Mutagenesis,Toxicology

Reference52 articles.

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