Development of an adverse outcome pathway for radiation-induced microcephaly via expert consultation and machine learning

Research output: Contribution to journalArticlepeer-review

Authors

  • Thomas Jaylet
  • Roel Quintens
  • Rafi Benotmane
  • Jukka Luukkonen
  • Ignacia Braga Tanaka III
  • Chrystelle Ibanez
  • Christelle Durand
  • Magdalini Sachana
  • Omid Azimzadeh
  • Christelle Adam-Guillermin
  • Knut Erik Tollefsen
  • Olivier Laurant
  • Karine Audouze
  • Olivier Armant

Institutes & Expert groups

  • Universite Paris Descartes - Universite Paris Descartes - T3S-UMRS1124
  • University of Eastern Finland
  • NIES - National Institute for Environmental Sciences
  • IRSN - Institute for Radioprotection and Nuclear Safety - Institut Radioprotection Sûreté Nucléaire
  • OECD NEA - Nuclear Energy Agenc
  • Bfs - Bundesamt Für Strahlenschutz - Federal Office for Radiation Protection
  • NIVA - Norwegian Institute for Water Research
  • NMBU - Norwegian University of Life Sciences

Documents & links

Abstract

Brain development during embryogenesis and in early postnatal life is particularly complex and involves the interplay of many cellular processes and molecular mechanisms, making it extremely vulnerable to exogenous insults, including ionizing radiation (IR). Microcephaly is one of the most frequent neurodevelopmental abnormalities that is characterized by small brain size, and is often associated with intellectual deficiency. Decades of research span from epidemiological data on in utero exposure of the A-bomb survivors, to studies on animal and cellular models that allowed deciphering the most prominent molecular mechanisms leading to microcephaly. The Adverse Outcome Pathway (AOP) framework is used to organize, evaluate and portray the scientific knowledge of toxicological effects spanning different biological levels of organizations, from the initial interaction with molecular targets to the occurrence of a disease or adversity. In the present study, the framework was used in an attempt to organize the current scientific knowledge on microcephaly progression in the context of ionizing radiation (IR) exposure. This work was performed by a group of experts formed during a recent workshop organized jointly by the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radioecology Alliance (ALLIANCE) associations to present the AOP approach and tools. Here we report on the development of a putative AOP for congenital microcephaly resulting from IR exposure based on discussions of the working group and we emphasize the use of a novel machine-learning approach to assist in the screening of the available literature to develop AOPs.

Details

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Radiation Biology
DOIs
Publication statusPublished - 18 Aug 2022

Keywords

  • Adverse outcome pathway, AOP, Microcephaly, Brain developent, Ionizing radiation

ID: 7933112