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Alessio Gamba
University of Liège

Alessio Gamba has a degree in Biotechnology followed by a Master degree in Functional Genomics and Bioinformatics. He started his scientific activity in the laboratory of Organic Chemistry and  Natural Substances and continued following courses on Computer Science and Systems Biology,  learning several programming languages used in computational biology. 

He spent nine months in Madrid (supported by Erasmus fellowship) in a laboratory focused on the study of genome-scale metabolism, followed by a period at the Cell Systems Modelling Group at  Oxford Brookes University, where he broadened his knowledge on omics data and metabolic analysis using Python. 

During his Ph.D. in Biochemical Sciences, he studied physico-chemical properties of protein interactions in the Biophysics Lab at University of Milan collaborating with the laboratory of Systems  Biology at Mario Negri Institute (Milan), investigating the relation between protein complexes and genetic diseases. He started working on computational toxicology, developing New Approach  Methodologies (NAMs), in the laboratory of Prof Benfenati at Mario Negri Institute. Recently, he started working in ONTOX project, as postdoc researcher at University of Liege  (Belgium), in the laboratory of Prof Geris, developing new computational approaches based on physiology and Systems Biology for the study of chemicals toxicities.

OpenTox Virtual Conference 2023

The nephron physiological map and kidney disease ontologies in ONTOX project 

Many predictive in silico models for toxicology are today available, providing accurate results for various toxicological endpoints. Even if they are animal-free approaches and avoid ethical concerns,  two main issues remain unsolved: 1) the predictions are based on animal data, which does not provide the best correlation when applied to human toxicity; 2) the models are often unable to explain the biological mechanisms of toxicity because they are developed solely based on the structure of toxic and non-toxic chemicals. To overcome these limitations, a new systems biology approach has been developed, based on Physiological Maps (PM) and associated disease ontologies, aimed at reducing animal tests in the framework of ONTOX project. 

I present here the PM and ontologies, as well as a workflow to assist the user in their setup, update, and validation. Starting from an expert-supervised literature review and database queries (e.g., Reactome,  WikiPathways), it is possible to assemble the PM using the CellDesigner software. Secondly, the PM is visualized online by MINERVA platform, adding several layers of information (e.g., interacting chemicals, associated phenotypes, transcriptomics), and building the ontology. Finally, the PM and ontology are reviewed by experts and can be stored on the BioStudies database. 

As example, the nephron PM presents the pathways for urine production, cytokines signaling, and vitamin D activation. It is associated with two ONTOX ontologies, developed to study tubular necrosis and crystallopathy. Being rich in biological mechanisms and related phenotypes, the PM and ontologies can serve for a parallel or subsequent development of adverse outcome pathways, as well as to build alterable models representing different cellular conditions. For these reasons, the PM and ontologies offer the possibility to investigate human toxicities from an innovative perspective, improving qualitatively and quantitatively the toxicological predictions.