Exploring chemical space in non-targeted analysis: a proposed ChemSpace tool

Area of Science:

• Environmental Chemistry
• Analytical Chemistry
• Toxicology

Background:

• Non-targeted analysis (NTA) with high-resolution mass spectrometry enables broad compound detection for exposure monitoring and toxicology.
• NTA workflows define a 'chemical space' of detectable compounds, but understanding workflow limitations remains challenging.
• Assessing non-detection as true absence versus workflow-induced false negatives is difficult due to non-standardized methods.

Purpose of the Study:

• To address the need for accessible chemical space mapping in NTA studies.
• To propose a tool for predicting compound detectability within NTA workflows.
• To enhance transparency and standardization in NTA by quantifying workflow constraints.

Main Methods:

• Combining existing predictive and analytical tools to generate compound detectability scores.
• Developing a hypothetical 'ChemSpaceTool' to map chemical space coverage of NTA workflows.
• Utilizing sample extraction, data acquisition, and data analysis parameters to define workflow chemical space.

Main Results:

• The proposed tool generates scores indicating the likelihood of a compound being detected and identified.
• Higher scores suggest greater detectability, while lower scores indicate a higher probability of false negatives.
• The tool can be used prospectively for library curation and retrospectively for filtering false detections.

Conclusions:

• Chemical space mapping improves NTA transparency and communication of false detection rates.
• Standardizing NTA through better understanding of workflow limitations enhances method comparison and reproducibility.
• The development of such a tool is crucial for broader NTA applications beyond research settings.