Evaluation Reports for TEBT-2026-0002 | Berkhout et al.

Evaluation reports for An AOP network of Neural Tube Defects (Berkhout et al. 2026)

This manuscript presents a comprehensive effort to derive from the literature a putative AOP network for neural tube defects (NTDs), with three sub-networks showing the role in NTDs of Wnt/PCP signalling, Grhl transcription, and Rho GTPases and EphA/ephrinA signalling. 

Qualitative, weighted AOP networks such as the ones presented in the manuscript are an important step in the development of formal, quantitative AOPs, a broader process that benefits from the peer-review and publication of intermediary research products such as this.

The manuscript is complete enough to be ready for peer-review, although there are limitations in the reporting of the literature search and screening methods that will need to be addressed. Although these methods are not fully clear, the consequences of the authors’ decisions are, so I feel comfortable inviting review in spite of the missing information.

From a triage perspective, the other important issue with the manuscript is a lack of detail around the methods for interpreting the collected data into the AOP networks. This leaves a significant methodological gap between the data collection methods and the analysis of data from the literature into the final AOP networks. Ideally this information would already have been provided; however, I feel that resolving this issue requires input from domain experts, which is why I am not requesting revisions prior to peer-review.