Fabrizio Mastrolorito, Maria Vittoria Togo, Nicola Gambacorta, Daniela Trisciuzzi, Viviana Giannuzzi, Fedele Bonifazi, Antonella Liantonio, Paola Imbrici, Annamaria De Luca, Cosimo Damiano Altomare, Fulvio Ciriaco, Nicola Amoroso, Orazio Nicolotti
Despite being extremely relevant for the protection of prenatal and neonatal health, the developmental toxicity (Dev Tox) is a highly complex endpoint whose molecular rationale is still largely unknown. The lack of availability of high-quality data as well as robust nontesting methods makes its understanding even more difficult. Thus, the application of new explainable alternative methods is of utmost importance, with Dev Tox being one of the most animal-intensive research themes of regulatory toxicology. Descending from TIRESIA (Toxicology Intelligence and Regulatory Evaluations for Scientific and Industry Applications), the present work describes TISBE (TIRESIA Improved on Structure-Based Explainability), a new public web platform implementing four fundamental advancements for in silico analyses: a three times larger dataset, a transparent XAI (explainable artificial intelligence) framework employing a fragment-based fingerprint coding, a novel consensus classifier based on five independent machine learning models, and a new applicability domain (AD) method based on a double top-down approach for better estimating the prediction reliability...
January 10, 2024: Chemical Research in Toxicology