Recent research in cancer biology, aging, microbial pathogenesis, and many other areas has revealed a key role for small molecule and lipid metabolites. The Metabolite Profiling Core Facility (Metabolomics Core Facility) was established in 2013 to support studies in this rapidly developing field.
Due to the extreme chemical diversity of small molecule and lipid metabolites – which greatly exceeds that of proteins and nucleic acids – the facility operates on a collaborative model in which experimental design, sample preparation, data collection, and data analysis are tailored to each study. We serve the Whitehead as well as the larger MIT community and external collaborators.
The facility is managed by Caroline A. Lewis, Ph.D., and employs two full time technicians, Tenzin Kunchok and Kayla Crowder, Ph.D.
The faculty advisor for the facility is Prof. David M. Sabatini, M.D., Ph.D.
An introduction to LC/MS-based metabolomics and an overview of the WI metabolomics facility.
If you are interested in performing a metabolite profiling experiment, please contact Caroline Lewis at calewis at wi.mit.edu to set up an initial consultation. Sample preparation, LC/MS, and data analysis methods vary widely depending on metabolite, sample type, and biological question. This page is intended to provide a general overview only.
We routinely perform relative quantitation of many polar metabolites (including amino acids,
glycolytic and TCA cycle intermediates) using hydrophilic interaction chromatography (HILIC). Analysis of lipids*, other non-polar metabolites and drugs is performed using reverse phase chromatography.
For many metabolites that have not previously been analyzed at our facility, we find that our existing methods are sufficient. However, in certain cases the sample preparation, chromatography and/or mass spectrometry portions of the analysis may need to be optimized or newly developed. Chemical standards are essential for this purpose. Chemical standards are also required to aid in the identification of metabolites found in untargeted analyses.
Several levels of analysis are available:
The core has extensive experience performing stable isotope tracing experiments (please note, this is not metabolic flux analysis), which can be conducted in collaboration with the Core. Please discuss your needs with Caroline Lewis.
The Metabolite Profiling Core Facility houses three liquid chromatography / mass spectrometry (LC/MS) systems.
We have two Thermo Scientific QExactive Orbitrap mass spectrometers and one Thermo Scientific Orbitrap ID-X mass spectrometer, all of which are capable of measuring mass-to-charge ratios with less than 5 ppm error and a resolution of up to 140,000 and can also collect MS/MS fragmentation data. Each mass spectrometer is coupled to a Dionex UltiMate 3000 ultra-high performance liquid chromatography (UPLC) system designed for pressures up to 1000 bar, permitting rapid separation times of ~30 minutes per sample.
Together with a library of several hundred synthetic standards, the combination of exact mass, fragmentation, and chromatographic retention time data permits the positive identification of most common cellular metabolites. Operating the mass spectrometers in either targeted or full-scan mode enables both hypothesis-driven and hypothesis-generating (untargeted) experiments to be performed.
Metabolite Profiling Core Facility charges consist of two categories: (1) per-sample fees and (2) data analysis & method development time. Project discussions, sample prep reagents, and help with manuscript preparation are always free, and there is no per-sample charge during new method development.
The main factors that determine data analysis time are the type of analysis (relative quantitation < absolute quantitation < untargeted analysis) and the number of metabolites. For a sample batch containing 20 or fewer samples, with 5 or fewer target metabolites, data analysis time typically does not exceed 1 hour for relative quantitation or 3 hours for absolute quantitation.
Price shown is the per sample run cost.
We offer all non-profit researchers a 20% discount on the per sample run cost for sample sets >32.
|Single polarity/ polarity switching (Most pHILIC and reverse phase methods)||Lipid/ dual polarity||Standard Curve*||Untargeted polar metabolomics||Method development/ Data analysis (per hour)|
|Per sample charge|
|Bi-phasic extraction for lipids (plasma or cell pellet)||$20.00|
|Protein precipitation for polar metabolites (plasma or cell pellet)||$15.00|
It is important to document use of the Whitehead Metabolite Profiling Core Facility in each publication, poster presentation or oral presentation. This helps us to be recognized by the institute and facilitates funding, and allows us to continue to support your research.
When data provided by the Metabolite Profiling Core Facility results in a publication, please contact us to let us know, and acknowledge the Core in your manuscript using a simple statement, such as the following:
“We thank the Metabolite Profiling Core Facility at the Whitehead Institute for running metabolomics samples and for data analysis”.
When a member of the Core has contributed significantly to a project, consider making them a co-author. The members of the Metabolite Profiling Core Facility are valued scientists; as such, their contributions to projects deserve to be recognized like any other co-author. For guidelines on including Core Facility personnel as co-authors, please see recommendations made by the Association for Bimolecular Resource Facilities (ABRF).
Human Metabolome Database (HMDB): Includes experimental and/or predicted MS/MS spectra for 114,224 metabolites.
KEGG: An important database of metabolites and metabolic pathways. Search for specific metabolites by name to view chemical structures and relevant pathways and enzymes. Alternatively, search for metabolic pathways (e.g., "glycolysis") to view and download pathway maps.
Metlin: A vast database containing experimental MS/MS spectra where available.
mzCloud: Thermo's fully curated spectral library with data collected solely on orbitraps.
Planet orbitrap (for all things Orbitrap)
Compound Discoverer Help: Help with Thermo's untargeted analysis software.
LIPID MAPS Lipidomics Gateway: An excellent resource for anything to do with lipids and lipidomics including protocols.
Metaboanalyst: A user-friendly, open-source platform for analyzing large-scale metabolomic datasets (e.g., the full polar metabolite panel analyzed by our facility). We have found the Statistical Analysis, Pathway Analysis, and Enrichment Analysis modules to be particularly useful. The Integrated Pathway Analysis tool is for combining metabolomics and gene expression data.
Lipid Mini-On - lipid enrichment analysis and visualization.
Metscape 3 for Cytoscape: Another tool for mapping your data onto metabolic gene and/or reaction networks, with the option of adding gene-expression data as well.
Journals are increasingly requesting that metabolomics data be deposited in data repositories. There are two main data repositories recommended specifically for metabolomics data:
Metabolomics Workbench (hosted by UCSD and sponsored by the NIH).
MetaboLights (hosted by EMBL-EBI)