Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Expanding Database Enables Discoveries in Emerging Field of Metabolomics

11.09.2012
Over the last decade, metabolomics has emerged as the newest of the “omic” sciences (following genomics and proteomics) to provide comprehensive biochemical information about cellular metabolism. This new field has revealed that many of the chemicals involved in or produced through metabolism are currently unknown, but may play vital and previously unappreciated roles in human health and disease.

A major hurdle in profiling both unknown and known metabolic compounds (“metabolites”) has been the scarce amount of reference data. But a team from The Scripps Research Institute has developed a massive, searchable online metabolite database that is transforming the field and being widely used in research on countless conditions including cancer and chronic pain.

The researchers describe the newly expanded database, called METLIN, and its potential benefits in the September issue of the journal Nature Biotechnology.

Getting Off the Beaten Path

Scientists once focused on only the major metabolic highways, well-known pathways such as glycolysis and the Krebs Cycle. New metabolomic studies have shown that other pathways and metabolites, however, also play critical roles in fundamental biological processes and the progression of disease.

“For decades biochemical studies have targeted only a handful of canonical metabolites, and comprehensive profiling has been mostly limited to genes and proteins,” said Gary Patti, a former postdoctoral fellow at Scripps Research now an assistant professor at Washington University in St. Louis who helped develop the database. But now he says the new field of metabolomics has emerged with huge promise for medical and other advancements. “I think it’s a really exciting time because the insights being provided by metabolomics are in some cases affecting the way in which we think about fundamental biochemistry,” he said.
The sheer number and complexity of metabolites offer scientists a colossal challenge. While DNA studies of genes that code for proteins offer clues about how many proteins there are and their functions, there’s no such map for metabolites—which include a huge range of chemical types, from amino acids, carbohydrates, and steroids to large, complex fatty acids. No one knows how many metabolites there are in humans, though the number may well be over 100,000, and other organisms may have their own unique arrays.

Digging In

Metabolites can be isolated and analyzed from almost any biological specimen, including tissues, blood, urine, and tumors. The most sensitive technique for analyzing metabolites is mass spectrometry. By using cutting-edge mass spectrometric technologies, the molecular weight of thousands of metabolites can be measured within a few minutes. Previously, researchers might spend days combing databases and other sources of information to identify just one metabolite of interest.
“If you don’t have a database like METLIN, the value of metabomic data would be very limited because each study would require manual searches and ultimately fail to culminate in enough reference data to arrive at conclusive metabolite identifications,” said team leader Gary Siuzdak, a metabolomics expert at Scripps Research.

It was against this landscape that Siuzdak’s group recognized the need for a consolidated and expanded metabolite database to meet the group’s own needs as it struggled to understand key metabolic processes. Efforts to build such a resource began in 2004 and the database they dubbed METLIN was initially built upon slowly. Information was scarce and entered manually, sometimes after curating chemistry books manually for new structural information. Researchers in the lab would compete to see who could add the most in a week. Simultaneously, the lab also began cataloging experimental tandem mass spectrometry data on these compounds and established the first of such resources to provide structural information on metabolites that can be used to identify metabolites.

Over the past few years, determined to accelerate their work, group members gained major momentum largely by partnering with companies like Sigma, Cayman, ChromaDex, as well as labs at Scripps Research (Boger), University of California, San Diego (Gerwick), the Joint BioEnergy Institute (Berkeley), and now Washington University (Patti) to facilitate acquisition of more molecules on which to generate tandem mass spectrometry data.
More than 10,000 Metabolites

Now METLIN includes more than 60,000 compounds with detailed, high-resolution tandem mass spectrometry information on more than 10,000 metabolites, by far the largest in the world. And the Siuzdak group is far from done. “METLIN is still growing as we speak,” said Ralf Tautenhahn, a senior research associate in Siuzdak’s lab and first author of the paper. “It’s a key tool for all our projects.” Once a metabolite is identified, researchers can begin working out how it functions in the body and in disease.

A key benefit of the database is that it goes beyond basic molecular weight—which might be the same for a range of different compounds. The tandem mass spectrometry data allows for a higher level of confidence in identifying these molecules from biological systems. This involves bombarding individual compounds with gas molecules, which causes them to break apart in unique ways. The weights of the resulting molecular fragments offer a sort of chemical signature for each metabolite that researchers can use to match unknowns more precisely.
Though you can search METLIN manually, the Scripps Research team has also developed software called XCMS Online that performs detailed automated searches. Users can input their own data and the coupled XCMS-METLIN system will come back with precise matches, or if there’s no direct match, it will identify structurally similar metabolites. “It really does accelerate the whole process of discovering new molecules associated with diseases and research in many different areas,” said Siuzdak.

Tapping the Potential

The Siuzdak team has already had major successes using the database. The researchers recently identified a metabolite that is associated with chronic pain when found in higher than normal levels. Finding ways to break down this metabolite or to prevent it from forming might lead to new treatment options for chronic pain sufferers.
Other projects are focused on cancer. While some researchers are looking for metabolites that might be present in the bloodstream as early indicators of cancer, Siuzdak’s group is identifying metabolites involved in cancer’s progression that might offer targets for new therapies. Patti’s lab at Washington University is further investigating the role of metabolism in chronic pain and is also looking into metabolite roles in aging and drug addiction.

But public access means METLIN’s reach stretches far beyond Scripps Research. “When we first started doing this, I was expecting a couple of hundred people in the world to use it,” said Siuzdak. Instead, he and his colleagues were shocked to find users by the thousands exploring a huge range of topics. Some researchers are looking for metabolites produced after ingestion of drugs to aid in forensics work; others are interested in ways to detect signs of pesticide ingestion.

“What’s really exciting about this is seeing that something we created is being so widely used,” said Siuzdak, “It definitely makes us feel good to think that we’ve accelerated the progress of science and allowed a lot of other scientists to do things they wouldn’t have been able to do otherwise.”

This research was funded by the California Institute of Regenerative Medicine (TR1-01219), the US National Institutes of Health (R24 EY017540, P30 MH062261, RC1 HL101034, P01 DA026146, L30 AG0 038036), and the US Department of Energy (FG02-07ER64325 and DE-AC0205CH11231).

In addition to Siuzdak, Patti, and Tautenhahn, the other authors on the paper, “An accelerated workflow for untargeted metabolomics using the METLIN database,” were Kevin Cho, Winnie Uritboonthai, and Zhengjiang Zhu, all from The Scripps Research Institute.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
For information:
Office of Communications
Tel: 858-784-8134
Fax: 858-784-8136
press@scripps.edu

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Health and Medicine:

nachricht TSRI researchers develop new method to 'fingerprint' HIV
29.03.2017 | Scripps Research Institute

nachricht Periodic ventilation keeps more pollen out than tilted-open windows
29.03.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>