Small molecules are essential components found throughout nature, playing a significant role in various fields such as
drug discovery,
diagnostics,
food science,
environmental monitoring,
forensics and more. Effectively addressing many
global challenges hinges on the comprehensive identification of small molecules in complex samples. These complex mixtures contain thousands of different molecules measurable in a single mass spectrometry run. The identification of unknown small molecules is considered a critical bottleneck in
metabolomics,
natural product research, and related fields, given that widely over 90% of all small molecules remain unknown. Commonly, analyses were based on targeted approaches that are limited to the rediscovery of known molecules. In contrast, untargeted analysis is a top-down strategy that avoids the need for a prior specific
hypothesis on expected small molecules. The focus shifts from asking, "Is molecule X present in the sample?" to "Which (unknown) molecules are present in the sample and might be relevant for downstream analysis?" SIRIUS is designed for the untargeted structural elucidation of unknown molecules, addressing various challenges: • The correct molecular structure is prominently ranked from an extensive list of candidates. This can be compared to a Google search where the optimal answer is expected to be among the top three. • The widespread use of
synthetic polymers in
food contact materials have raised significant concerns about
plastic contamination in food and beverages. A non-targeted approach to analysis is essential for uncovering both known and unknown contaminants. Researchers screened suspected and unanticipated chemicals in a variety of liquor samples using SIRIUS. • SIRIUS is used in
forensic science to analyze the chemical changes during
decomposition, helping to understand microbial networks and potentially predict the
time since death. •
Neonatal dried blood spots are important for
newborn screening and a powerful source for investigating the potential metabolic
etiologies of various diseases using untargeted LC-MS-based metabolomics. Researchers used SIRIUS to investigate the stability of metabolites and classes of molecules in neonatal dried blood spot biobanks. •
Marine microorganisms offer a rich source of
bioactive compounds with unique structures and remarkable biological activity. This makes them an important resource for the search for new
therapeutic compounds. Researchers are using SIRIUS, to narrow down the search to the most promising microorganisms. • Pediatric
asthma poses diagnostic challenges due to its variable presentation.
Breath analysis could be a game-changer in pediatric allergic asthma management. By identifying unique exhaled metabolic signatures using SIRIUS, researchers developed an approach to diagnose children with allergic asthma. •
Thiacloprid is a first-generation, widely used,
neonicotinoid insecticide. Its persistence in the environment and potential adverse effects on human health have raised significant concerns. Elucidating the impurity profile of pesticides is crucial for assessing their environmental impact and potential risks, and setting acceptable limits for impurities. Using SIRIUS, researchers demonstrated an approach for identifying structurally related impurities in pesticides. • Under certain conditions, two
bacterial species can thrive together in a dual-species
biofilm. The cooperation between
P. aeruginosa and
S. aureus in
cystic fibrosis leads to increased disease severity. Using SIRIUS, researchers identified a metabolite that could be related to the increased
pathogenesis of this dual-species biofilm in cystic fibrosis. • Our skin hosts a diverse community of
microorganisms known as the
skin microbiota. Using SIRIUS, researchers identified changes in the skin metabolome that are more pronounced than changes in the microbial composition, suggesting that even subtle shifts in microbial abundance can lead to significant effects on the skin. == Limitations ==