Release Notes

HMDB 5.0 brings a number of important improvements and upgrades to the database. These should make the HMDB more useful and more appealing to a larger cross-section of users. In particular, these improvements include: (i) a significant increase in the number of metabolite entries (from 114 100 to 217 920 compounds); (ii) enhancements to the quality and depth of metabolite descriptions; (iii) the addition of new structure, spectral and pathway visualization tools; (iv) the inclusion of many new and much more accurately predicted spectral data sets, including predicted NMR spectra, more accurately predicted MS spectra, predicted retention indices and predicted collision cross section data and (v) enhancements to the HMDB’s search functions to facilitate better compound identification. Many other minor improvements and updates to the content, the interface, and general performance of the HMDB website have also been made. Overall, we believe these upgrades and updates should greatly enhance the HMDB’s ease of use and its potential applications not only in human metabolomics but also in exposomics, lipidomics, nutritional science, biochemistry and clinical chemistry.

HMDB 4.0 represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB’s chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC–MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.

The substantial expansion of annotated metabolites in HMDB 4.0 has necessitated an important change to the HMDB’s original 5-digit accession numbers. Since its inception, the HMDB has used unique accession numbers consisting of a 4-letter prefix (HMDB) and a 5-number suffix. With the release of HMDB 4.0, the 5-digit accession numbers have had to be adjusted to a 7-digit suffix to maintain consistency. This has been accomplished by appending two zeroes after the 4-letter prefix and before each 5-number suffix (e.g. HMDB00001 becomes HMDB0000001). In order to minimize disruption in dependent applications, the original 5-digit accession numbers have become secondary accession numbers to their 7-digit counterparts. This ensures that access to metabolite entries via their URLs is preserved.

Version 3.0 of the HMDB is has been significantly expanded and enhanced over the 2009 release (version 2.0). In particular, the number of annotated metabolite entries has grown from 6500 to more than 37,166. This enormous expansion is a result of the inclusion of both “Confirmed” metabolites (those with measured concentrations or experimental confirmation of their existence) and “Expected” metabolites (those for which biochemical pathways are known or human intake/exposure is frequent but the compound has yet to be detected in the body). The latest release also has greatly increased the number of metabolites with biofluid or tissue concentration data, the number of compounds with reference spectra and the number of data fields per entry. In addition to this expansion in data quantity, new database visualization tools and new data content has been added or enhanced. These include better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps.

Version 2.5 of the HMDB represents an evolution in the richness and depth of the data available in the HMDB. In addition, it includes several enhancements and refinements to the search and visualization tools available on the website. The following table provides a summary of the major changes and enhancements in version 2.5.

Database feature/content status	HMDB Version 1.0	HMDB Version 2.0	HMDB Version 2.5
Number of metabolites	2180	6826	7982
Number of unique metabolite synonyms	27700	43882	69287
Number of compounds with disease links	862	1002	1064
Number of compounds with biofluid or tissue concentration data	883	4413	4857
Number of compounds with urine concentration data	231	472	782
Number of compounds with serum concentration data	174	3976	4418
Number of compounds with cerebrospinal fluid concentration data	47	360	363
Number of compounds with experimental reference 13C NMR spectra	380	784	899
Number of compounds with experimental reference 1H NMR spectra	385	792	905
Number of compounds with reference MS-MS spectra	390	799	2654
Number of compounds with reference GC-MS spectra	0	279	318
Number of human-specific pathway maps	26	58	71
Number of compounds in the Human Metabolome Library (HML)	607	920	1016
Number of HMDB data fields	91	102	111
Pathway search/browse capability	No	Yes	Enhanced
Disease search/browse capability	No	Yes	Enhanced
Chemical class search/browse capability	No	Yes	Enhanced
Chemical substructure search capability	No	Yes	Enhanced
Biofluid search/sort tools	No	Yes	Enhanced
Advanced (multipeak or multicompound) NMR search	No	Yes	Enhanced
Advanced (multipeak or multicompound) MS-MS search	No	Yes	Enhanced
Advanced (retention index or MS peak) GC-MS search	No	Yes	Enhanced

• Rebuilt website
• Moved to faster server (quad-core X-Serve)
• Version 2.0 of the HMDB now has detailed information on 6534 experimentally confirmed metabolites, representing an expansion of nearly 300% over version 1.0. Currently about 60% of the metabolites in the HMDB have been identified or confirmed by the HMDB's team of analytical chemists using NMR, LC-MS or GC-MS methods applied to a variety of human biofluids. Likewise, approximately 45% of the metabolites in the HMDB have been identified and archived through literature surveys or electronic data mining.
• Metabocards have been updated - they are now easier to parse and several data fields that had mutliple pieces of information in a single field have been split up.

• Initial HMDB release