Streamlit

structure-masst.gnps2.org

A Perspective on Unintentional Fragments and Their Impact on the Dark Metabolome, Untargeted Profiling, Molecular Networking, Public Data, and Repository Scale Analysis

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.

pubs.acs.org

Increasing the Scale of the Mass Spectrometry Query Language Compendium with Explainable AI

A significant bottleneck in metabolomics data interpretation is the effective use of domain knowledge to assign structural information based on fragmentation patterns. The mass spectrometry query lang...

pubs.acs.org

A Perspective on Unintentional Fragments and their Impact on the Dark Metabolome, Untargeted Profiling, Molecular Networking, Public Data, and Repository Scale Analysis.

In/post-source 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 don’ts 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.

doi.org

Reverse Spectral Search Reimagined: A Simple but Overlooked Solution for Chimeric Spectral Annotation

The exponential growth of untargeted metabolomics data, now reaching billions of mass spectra in public repositories, benefits from reannotation strategies for data reuse. While tandem mass spectromet...

doi.org

Computationally unmasking each fatty acyl C=C position in complex lipids by routine LC-MS/MS lipidomics - Nature Communications

Physiologically relevant omega-positions of double bonds in fatty acyls in complex lipids can now only be identified with specialized instrumentation. Here, the authors present a computational approac...

nature.com

The mass spectrometry of microbiome-mediated metabolism of food: challenges and opportunities

With the exception of molecules acquired through the lungs, skin absorption, or part of a medication regime, nearly all molecules in our bodies origin…

sciencedirect.com

Enhancing tandem mass spectrometry-based metabolite annotation with online chemical labeling - Nature Communications

To improve annotation in non-targeted metabolomics studies, authors develop a Multiplexed Chemical Metabolomics (MCheM) platform, combining post-column derivatization with integrated data processing. ...

nature.com

An evaluation methodology for machine learning-based tandem mass spectra similarity prediction - BMC Bioinformatics

Background Untargeted tandem mass spectrometry serves as a scalable solution for the organization of small molecules. One of the most prevalent techniques for analyzing the acquired tandem mass spectr...

bmcbioinformatics.biomedcentral.com

GitHub - rformassspectrometry/SpectriPy: Interfacing R's Spectra package with the Python world.

Interfacing R's Spectra package with the Python world. - rformassspectrometry/SpectriPy

github.com

The microbiome diversifies long- to short-chain fatty acid-derived N-acyl lipids

Mass spectrometry data mining tools enabled the creation of an MS/MS spectral library containing hundreds of N-acyl lipids, including conjugates with short-chain fatty acids. This resource enabled the...

cell.com

Milk phospholipid-coated lipid droplets modulate the infant gut microbiota and metabolome influencing weight gain - Microbiome

Background The supramolecular structure and composition of milk fat globules in breast milk is complex. Lipid droplets in formula milk are typically smaller compared to human milk and differ in their ...

microbiomejournal.biomedcentral.com

The changing metabolic landscape of bile acids – keys to metabolism and immune regulation - Nature Reviews Gastroenterology & Hepatology

Bile acids have important roles in human metabolism and immune regulation. In this Perspective, Dorrestein and colleagues discuss the technologies and data science-related approaches that are improvin...

nature.com

A Multi-Organ Murine Metabolomics Atlas Reveals Molecular Dysregulations in Alzheimer’s Disease

The etiology of Alzheimer’s Disease (AD) remains largely unclear but is likely driven by gene-environment interactions. Here, we present a multi-organ untargeted metabolomics dataset (2,271 samples) g...

biorxiv.org