A Perspective on Unintentional Fragments and Their Impact on the Dark Metabolome, Untargeted Profiling, Molecular Networking, Public Data, and Repository Scale Analysis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00643664" target="_blank" >RIV/61388963:_____/25:00643664 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/jacsau.5c01063" target="_blank" >https://doi.org/10.1021/jacsau.5c01063</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/jacsau.5c01063" target="_blank" >10.1021/jacsau.5c01063</a>
Alternative languages
Result language
angličtina
Original language name
A Perspective on Unintentional Fragments and Their Impact on the Dark Metabolome, Untargeted Profiling, Molecular Networking, Public Data, and Repository Scale Analysis
Original language description
In/postsource fragments (ISFs) arise during electrospray ionization or ion transfer in mass spectrometry when molecular bonds break, generating ions that can complicate data interpretation. Although ISFs have been recognized for decades, their contribution to untargeted metabolomics-particularly in the context of the so-called dark matter (unannotated MS or MS/MS spectra) and the dark metabolome (unannotated molecules)-remains unsettled. This ongoing debate reflects a central tension: while some caution against overinterpreting unidentified signals lacking biological evidence, others argue that dismissing them too quickly risks overlooking genuine molecular discoveries. These discussions also raise a deeper question: what exactly should be considered part of the metabolome? As metabolomics advances toward large-scale data mining and high-throughput computational analysis, resolving these conceptual and methodological ambiguities has become essential. In this perspective, we propose a refined definition of the dark metabolome and present a systematic overview of ISFs and related ion forms, including adducts and multimers. We examine their impact on metabolite annotation, experimental design, statistical analysis, computational workflows, and repository-scale data mining. Finally, we provide practical recommendations-including a set of dos and do nots for researchers and reviewers-and discuss the broader implications of ISFs for how the field explores unknown molecular space. By embracing a more nuanced understanding of ISFs, metabolomics can achieve greater rigor, reduce misinterpretation, and unlock new opportunities for discovery.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JACS Au
ISSN
2691-3704
e-ISSN
2691-3704
Volume of the periodical
5
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
23
Pages from-to
5828-5850
UT code for WoS article
001629437200001
EID of the result in the Scopus database
2-s2.0-105025351117