METLIN is an openly accessible online database focused on small biological molecules called metabolites, such as sugars, fats, and amino acids. These molecules are fundamental to numerous processes within living organisms, including energy production, signaling, and structural integrity. METLIN serves as a continuously expanding resource for scientists studying these components of life.
The Purpose of a Metabolomics Database
Metabolomics is the study of all metabolites within a biological system, collectively known as the “metabolome.” Studying the metabolome provides insights into an organism’s physiological state.
A database like METLIN helps scientists manage and interpret the diverse molecules within a metabolome. Researchers use it to pinpoint and characterize thousands of distinct molecules in various biological samples. This resource helps them understand how molecular profiles change in response to conditions like disease or pharmaceutical treatments.
This organized data allows for systematic comparison of metabolite profiles. By identifying specific changes in metabolite concentrations or the presence of new compounds, scientists can uncover molecular signatures linked to health and disease. This supports the development of new diagnostic tools and therapeutic strategies.
What Data is in METLIN?
METLIN contains highly specific and diverse information for a vast array of molecules, extending beyond just metabolites to include drugs, xenobiotics, and toxicants. Each entry provides fundamental chemical identifiers, such as the molecule’s systematic name, its precise chemical formula, and a detailed representation of its three-dimensional molecular structure. This foundational information is crucial for accurately identifying and differentiating compounds.
The core strength of the METLIN database lies in its extensive collection of experimental tandem mass spectrometry (MS/MS) data. This type of data serves as a highly specific molecular “fingerprint” or “barcode” for each compound. During MS/MS analysis, a molecule is first isolated and then intentionally fragmented into smaller, characteristic pieces. The unique pattern and masses of these resulting fragments are highly indicative of the original molecule’s identity.
METLIN’s repository features MS/MS data acquired from various types of mass spectrometry instruments, ensuring broad utility for researchers using different platforms. The data is systematically collected in both positive and negative ionization modes and across multiple collision energies, providing a comprehensive and robust dataset for each molecule. This multi-faceted data collection enhances the reliability of molecular identification by capturing diverse fragmentation patterns.
The database is renowned for its high-resolution data, which provides exceptionally accurate and finely detailed molecular fingerprints. This precision is paramount for distinguishing between molecules with very similar masses, minimizing ambiguity in complex biological samples. As of December 2023, METLIN housed experimental MS/MS data for over 930,000 distinct molecular standards, making it the largest repository of its kind and continuously expanding with new entries.
How Researchers Use METLIN
Scientists frequently employ METLIN to identify unknown molecules discovered during their analysis of biological samples. When a researcher analyzes a biological sample and detects an unrecognized molecule, they then use a mass spectrometry instrument to generate the unique MS/MS “fingerprint” of this unidentified compound.
The researcher can upload this experimental MS/MS data, often in standard formats like mzXML or mzData, directly into the METLIN database. Alternatively, they can perform searches based on parameters such as the molecule’s exact mass, chemical formula, or specific fragment ions. METLIN then efficiently compares the uploaded or queried fingerprint against its expansive library of known molecular fingerprints, utilizing advanced algorithms like X-Rank.
Upon finding a match, the database provides the identity of the molecule, along with its full chemical profile and links to external resources like the Kyoto Encyclopedia of Genes and Genomes (KEGG) for further information. This identification process is applied in diverse research areas, such as pinpointing novel biomarkers for the early detection of diseases or understanding the metabolic changes associated with specific conditions like cancer or diabetes. Researchers also use METLIN to investigate the impact of pharmaceutical drugs on the body’s metabolism, observing how drug administration alters endogenous metabolite levels.
The database also supports more advanced searches, including neutral loss and fragment similarity searches, which are particularly useful for characterizing molecules that do not have an exact match in the database. This capability allows scientists to infer substructural information about truly unknown compounds. By comparing patterns of fragmentation, researchers can gain clues about the chemical components of novel molecules, facilitating their eventual full identification.
The Technology Behind the Data
The precise and extensive molecular information contained within the METLIN database is fundamentally derived from a powerful analytical technique known as mass spectrometry. This technology functions as an extraordinarily sensitive instrument capable of measuring the mass-to-charge ratio of individual molecules with remarkable accuracy. It operates by ionizing molecules, converting them into charged particles, which are then separated and detected based on their unique mass and charge characteristics.
Specifically, the data for METLIN is largely generated using tandem mass spectrometry (MS/MS), a more advanced form of this technique. In MS/MS, a selected charged molecule, known as a precursor ion, is isolated and then intentionally broken apart into smaller, characteristic fragment ions. The unique pattern and precise masses of these fragments are then recorded. This detailed fragmentation profile creates the highly specific “fingerprints” that form the backbone of the METLIN database, providing the experimental evidence necessary for identifying hundreds of thousands of different chemical entities.