Identification of small molecules using accurate mass MS/MS search

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Bioinformatics

Background:

• Tandem mass spectrometry (MS/MS) is crucial for annotating small molecules across diverse scientific domains.
• Annotation confidence relies heavily on instrumental parameters, data acquisition methods, library scoring, and post-curation.

Purpose of the Study:

• To critically review factors influencing MS/MS spectral annotation accuracy.
• To survey available MS/MS databases and search software tools.
• To discuss advanced computational methods and community efforts in spectral data sharing.

Main Methods:

• Critical discussion of parameters affecting MS/MS search results (e.g., mass accuracy, isolation width, intensity thresholds).
• Survey of public and commercial MS/MS spectral databases (NIST, MassBank, MoNA, LipidBlast, METLIN).
• Review of software tools for MS/MS library searching (NIST MS Search, MS-DIAL, Mass Frontier).

Main Results:

• Identification of key parameters influencing MS/MS annotation confidence.
• Overview of the landscape of MS/MS databases and search algorithms.
• Exploration of advanced in silico spectral generation and community data-sharing initiatives.

Conclusions:

• Optimizing MS/MS search parameters and leveraging comprehensive databases/software are vital for accurate small molecule annotation.
• Advanced computational methods and collaborative data sharing are essential for future progress in metabolomics and related fields.