Scannotation: A Suspect Screening Tool for the Rapid Pre-Annotation of the Human LC-HRMS-Based Chemical Exposome

In an increasingly chemically polluted
environment, rapidly characterizing
the human chemical exposome (i.e., chemical mixtures accumulating
in humans) at the population scale is critical to understand its impact
on health. High-resolution mass spectrometry (HRMS) profiling of complex
biological matrices can theoretically provide a comprehensive picture
of chemical exposures. However, annotating the detected chemical features,
particularly low-abundant ones, remains a significant obstacle to
implementing such approaches at a large scale. We present Scannotation
(https://github.com/scannotation/Scannotation_software), an
automated and user-friendly suspect screening tool for the rapid pre-annotation
of HRMS preprocessed data sets. This software tool combines several
MS1 chemical predictors, i.e., m/z, experimental and predicted retention times, isotopic patterns,
and neutral loss patterns, to score the proximity between features
and suspects, thus efficiently prioritizing tentative annotations
to verify. Scannotation and MS-DIAL4 were used to annotate blood serum
samples of 75 Breton adolescents. Scannotation’s combination
of MS1-based chemical predictors allowed us to annotate 89 chemically
diverse environmental compounds with high confidence (confirmed by
MS2 when available). These compounds included 62% of emerging molecules,
for which no toxicological or human biomonitoring data are reported
in the literature. The complementarity observed with MS-DIAL4 results
demonstrates the relevance of Scannotation for the efficient pre-annotation
of large-scale exposomics data sets.