"From Protein Toxins to Applied Toxicological Testing" virtual workshop identifies the need for a bioinformatic framework to assess novel food protein safety.

On October 21-22, 2020 the HESI (Health and Environmental Sciences Institute) Protein Allergens, Toxins, and Bioinformatics Committee, and the Society of Toxicology Food Safety Specialty Section co-hosted a virtual workshop titled "From Protein Toxins to Applied Toxicological Testing". The workshop focused on the safety assessment of novel proteins contained in foods and feeds, was globally represented by over 200 stakeholder attendees, and featured contributions from experts in academia, government and non-government organizations, and agricultural biotechnology developers from the private sector. A range of topics relevant to novel protein safety were discussed, including: the state of protein toxin biology, modes and mechanisms of action, structures and activity, use of bioinformatic analyses to assess the safety of a protein, and ways to leverage computational biology with in silico approaches for protein toxin identification/characterization. Key outcomes of the workshop included the appreciation of the complexity of developing a definition for a protein toxin when viewed from the perspective of food and feed safety, confirming the need for a case-by-case hypothesis-driven interpretation of bioinformatic results that leverages additional metadata rather than an alignment threshold-driven interpretation, and agreement that a "toxin protein database" is not necessary, as the bioinformatic needs for toxin detection may be accomplished by existing databases such as Pfam and UniProtKB/Swiss-Prot. In this paper, a path forward is proposed.

The UniProt-GO Annotation database in 2011.

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.uk/GOA) is a comprehensive set of evidenced-based associations between terms from the Gene Ontology resource and UniProtKB proteins. Currently supplying over 100 million annotations to 11 million proteins in more than 360,000 taxa, this resource has increased 2-fold over the last 2 years and has benefited from a wealth of checks to improve annotation correctness and consistency as well as now supplying a greater information content enabled by GO Consortium annotation format developments. Detailed, manual GO annotations obtained from the curation of peer-reviewed papers are directly contributed by all UniProt curators and supplemented with manual and electronic annotations from 36 model organism and domain-focused scientific resources. The inclusion of high-quality, automatic annotation predictions ensures the UniProt GO annotation dataset supplies functional information to a wide range of proteins, including those from poorly characterized, non-model organism species. UniProt GO annotations are freely available in a range of formats accessible by both file downloads and web-based views. In addition, the introduction of a new, normalized file format in 2010 has made for easier handling of the complete UniProt-GOA data set.

Tox-Prot, the toxin protein annotation program of the Swiss-Prot protein knowledgebase.

The Tox-Prot program was initiated in order to provide the scientific community a summary of the current knowledge on animal protein toxins. The aim of this program is to systematically annotate all proteins which act as toxins and are produced by venomous and poisonous animals. Venomous animals such as snakes, scorpions, spiders, jellyfish, insects, cone snails, sea anemones, lizards, some fish, and platypus are equipped with a specialized organ to inject venom in their prey. In contrast, poisonous animals such as some fish or worms, lack such organs. Each toxin is annotated according to the quality standards of Swiss-Prot. This means providing a wealth of information that includes the description of the function, domain structure, subcellular location, tissue specificity, variants, similarities to other proteins, keywords, etc. In the framework of this program, particular care has been made to capture what is known on the function and mode of action, posttranslational modifications and 3D structural data which are all relatively abundant in the field of protein toxins. Researchers are welcome to contribute their knowledge to the scientific community by submitting relevant findings to Swiss-Prot concerning toxins at Tox-Prot@isb-sib.ch. More information on Tox-Prot can be found at http://www.expasy.org/sprot/tox-prot.

The UniProtKB/Swiss-Prot Tox-Prot program: A central hub of integrated venom protein data.

Animal toxins are of interest to a wide range of scientists, due to their numerous applications in pharmacology, neurology, hematology, medicine, and drug research. This, and to a lesser extent the development of new performing tools in transcriptomics and proteomics, has led to an increase in toxin discovery. In this context, providing publicly available data on animal toxins has become essential. The UniProtKB/Swiss-Prot Tox-Prot program (http://www.uniprot.org/program/Toxins) plays a crucial role by providing such an access to venom protein sequences and functions from all venomous species. This program has up to now curated more than 5000 venom proteins to the high-quality standards of UniProtKB/Swiss-Prot (release 2012_02). Proteins targeted by these toxins are also available in the knowledgebase. This paper describes in details the type of information provided by UniProtKB/Swiss-Prot for toxins, as well as the structured format of the knowledgebase.

Animal Toxins: How is Complexity Represented in Databases?

Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database. ArachnoServer and ConoServer focus on spider toxins and cone snail toxins, respectively. UniProtKB, a generalist protein knowledgebase, has an animal toxin-dedicated annotation program that includes toxins from all venomous animals. Finally, the ATDB metadatabase compiles data and annotations from other databases and provides toxin ontology.