It is time for top-down venomics

The protein composition of animal venoms is usually determined by peptide-centric proteomics approaches (bottom-up proteomics). however,this technique cannot,in most cases,distinguish among toxin proteoforms,herein called toxiforms,because of the protein inference problem. top-down proteomics (tdp) analyzes intact proteins without digestion and provides high quality data to identify and characterize toxiforms. denaturing top-down proteomics is the most disseminated subarea of tdp,which performs qualitative and quantitative analyzes of proteoforms up to ~30 kda in high-throughput and automated fashion. on the other hand,native top-down proteomics provides access to information on large proteins (> 50 kda) and protein interactions preserving non-covalent bonds and physiological complex stoichiometry. the use of native and denaturing top-down venomics introduced novel and useful techniques to toxinology,allowing an unprecedented characterization of venom proteins and protein complexes at the toxiform level. the collected data contribute to a deep understanding of venom natural history,open new possibilities to study the toxin evolution,and help in the development of better biotherapeutics. © 2017 the author(s).