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Abstract
Venom research has been continuously enhanced by technological advances. High-throughput technologies are changing the classical paradigm of hypothesis-driven research to technology-driven approaches. However, the thesis advocated in this paper is that full proteome coverage at locus-specific resolution requires integrating the best of both worlds into a protocol that includes decomplexation of the venom proteome prior to liquid chromatography–tandem mass spectrometry matching against a species-specific transcriptome. This approach offers the possibility of proof-checking the species-specific contig database using proteomics data. Immunoaffinity chromatography constitutes the basis of an antivenomics workflow designed to quantify the extent of cross-reactivity of antivenoms against homologous and heterologous venom toxins. In the author’s view, snake venomics and antivenomics form part of a biology-driven conceptual framework to unveil the genesis and natural history of venoms, and their within- and between-species toxicological and immunological divergences and similarities. Understanding evolutionary trends across venoms represents the Rosetta Stone for generating broad-ranging polyspecific antivenoms.
Acknowledgements
Funding for the research described in this paper was provided by grants BFU2010-17373 from the Ministerio de Ciencia é Innovación (currently, Ministerio de Economía y Competitividad), Madrid; PROMETEO/2010/005 from the Generalitat Valenciana; CRUSA-CSIC (2009CR0021) and CYTED project BIOTOX P211RT0412.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Though initially conceived as a technological platform, next-generation snake venomics also represents a conceptual framework for the comprehensive analysis of venoms.
The availability of species-specific full-length venom gland transcript sequences as a reference database has greatly enhanced the efforts of mass spectrometry-based venom proteomics, circumventing the need for de novo mass spectrometry sequencing.
Full proteome coverage at locus-specific resolution is within the reach of current omics technologies, but requires integrating hypothesis-driven and technology-driven approaches. The need to decomplex the venom proteome represents an opportunity to quantitate the relative abundances of the different venom components.
An interesting derivation of next-generation snake venomics is the possibility of using the proteomics data to proof checking the accuracy of the assembly and translation of the transcriptome database.
The recent publications of the King cobra and the Burmese python genomes provide insights into the biology and the evolution of venom toxin genes at the genome structural level and represent the foundation of comparative snake genomics.
Developing the full potential of venom research requires the integration of data across the biological system within the frame of an evolutionary hypothesis.
Bridging the gap between genotype and phenotype requires an understanding of the mechanisms controlling the accelerated evolution of venom toxins and the regulatory components of the venom secretory system.
Genus-wide venomics, antivenomics and biogeographical studies will reveal the chemical and immunological space of venoms at different taxonomic levels. This information is relevant for venomics to meet the challenge of snakebite envenomings.
Understanding evolutionary trends across venoms represents the Rosetta Stone for generating broad-ranging polyspecific antivenoms.