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Then and Now at EMSL: A Focus on “Omics”

Scientists at EMSL look to a bright omics future rooted in a history of innovation

Catie Himes |
Eclipse mass spectrometer with samples

The Eclipse mass spectrometer is the latest evolution of the AMT Tag—the game-changing approach developed by Environmental Molecular Sciences Laboratory scientists in the early 2000s. (Photo by Genoa Blankenship | Pacific Northwest National Laboratory)

Imagine you’re standing in a bustling city. You take a picture—in that image are a person walking, a person biking, and a car. While the picture can tell you a lot, it’s impossible to get a detailed idea of how fast each subject is moving and how they’re interacting.

You decide to take a video next, and you can now observe things like subjects’ speed and location relative to each other. It provides a wealth of information that the picture cannot.

This is the analogy Mary Lipton, a chemist and leader of the Biomolecular Pathways Integrated Research Platform at the Environmental Molecular Sciences Laboratory, uses to summarize the future vision for EMSL’s already established world-class research capabilities in omics, a term that encompasses any field of study in biology that ends in “-omics,” such as proteomics, metabolomics, and lipidomics, among many others.

“If you take a movie, you can see the cars going 50 miles per hour, the bikes going 30 miles per hour, and people walking at 5 miles per hour and how they’re progressing relative to one another,” says Lipton. “We want to do the same thing in biology to understand different rates of processes, which you can’t get with a snapshot.”

Until now, omics have primarily relied on biological “snapshots” to understand the world around us. In many ways, EMSL is poised to propel the omics field into the world of biological motion pictures. But more on that later—first, we need to take a step back in time.

What are omics?

Omics is a varied and wide-ranging field that can be categorized into specific areas, including the proteomics (study of proteins), metabolomics (study of metabolites), and lipidomics (study of lipids) fields already mentioned. But there’s also genomics, transcriptomics, epigenomics… the list goes on.

A sample is loaded into the Nanodroplet Processing in One Pot for Trace Samples platform.
The Nanodroplet Processing in One Pot for Trace Samples (nanoPOTS) sampling platform is one of the proteomics instruments available at the Environmental Molecular Sciences Laboratory. Its chip, shown here, allows sample processing at nanoliter volumes. These tiny volumes enable orders of magnitude more information to be gleaned than with standard sample sizes. (Photo by Andrea Starr | Pacific Northwest National Laboratory)

EMSL has premier capabilities in proteomics, metabolomics, and lipidomics. Some proteomics highlights include (scientist jargon incoming) bottom-up proteomics, top-down proteomics, and the Nanodroplet Processing in One Pot for Trace Samples (nanoPOTS) sample platform. In metabolomics, some key EMSL capabilities include mass spectrometry instruments, liquid nuclear magnetic resonance, and spatial metabolomics through mass spectrometry imaging. All in all, EMSL’s omics suite is broad and expansive, encompassing a number of specialty tools and in-house expertise.

But this impressive inventory didn’t just appear out of nowhere—it’s the result of over two decades of innovation and development.

A (brief) history of omics at EMSL

It all started in the early 2000s, when the science community was first exploring how to do proteomics analyses. EMSL scientists (including Lipton) developed an experimental platform that could use liquid chromatography separations with a combination of two different techniques: identifying peptides through low-resolution tandem mass spectrometry based analysis and high-resolution mass measurements using Fourier-transform ion cyclotron resonance (FTICR) instruments. FTICR is especially useful for rapidly identifying and quantifying large numbers of peptides in biological systems. These methods eventually evolved for use in higher-resolution and higher-throughput studies.

The scientists called their innovation the Accurate Mass and Time (AMT) Tag approach. AMT Tag was the first to combine liquid chromatography separations with measurements from both high-resolution, high-accuracy FTICR, and tandem mass spectrometry. While the latter technology was used to identify the peptides and to create a library of peptide candidates, the former was used to rapidly quantify peptides in experiments with large numbers of samples.

Not only was AMT Tag revolutionary for work done at EMSL, it opened the frontier to proteomics as a field of study—those original instruments were the basis for EMSL’s current omics platform. They were also the inspiration behind a mass spectrometer instrument developed by Thermo Scientific, the latest version of which is called the Eclipse, that could do the work of AMT Tag’s two instruments in one.

You could say the rest is history. But it was also just the beginning—from there, the field of proteomics has been based on those original innovations over 20 years ago.

“EMSL’s initial proteomics capability forged the path for the current platform that everybody uses for proteomics,” says Lipton. “This is an overarching success that started with the AMT Tag approach.”

What do we do with all that omics data?

woman stands on stairs near a nuclear magnetic resonance instrument
The Multiomics Analysis Portal helps researchers analyze a variety of omics data, including nuclear magnetic resonance (NMR) metabolomics data from instruments like the 750 megahertz Bokan NMR spectrometer. (Photo by Andrea Starr | Pacific Northwest National Laboratory)

The colossal progress in this field also comes with its own set of challenges. Biological research data produced during omics and other studies is typically both large and complex, sometimes hindering discovery. To help combat this and to offer researchers solutions for analyzing their own data even if they don’t have expertise in programming methods or data-processing techniques, EMSL developed the Multiomics Analysis Portal (MAP).

The goal of MAP was to create a platform that would enable non-programmers/statisticians to analyze their own data. MAP helps guide researchers through the steps in their analysis and avoid using a method that isn’t appropriate for their data.

“MAP is very user friendly for the non-expert,” says Kelly Stratton, a biostatistician and leader of EMSL’s Data Transformations Integrated Research Platform. “Multiple tools can be housed in the portal, allowing the analysis to be tailored to the specific needs of the data. More tools can also be added, making MAP customizable.”

Alongside EMSL’s variety of omics tools available, access to MAP is available to those with a NEXUS login and can be requested as a resource when applying to EMSL’s open proposal calls. For additional information on MAP, view the recent webinar, co-presented by Stratton and Lisa Bramer, the principal investigator for MAP.

The future of omics at EMSL

Developing new instrumentation is a rich and dynamic arena with many players. EMSL has and will remain invested in the cutting edge of tool innovation, while taking it a step further. One of the unique capabilities that EMSL offers is a combination of state-of-the-art instrumentation and equipment with a wealth of in-house expertise and technical know-how.

“EMSL’s emerging technologies are tightly coupled to the biological questions proposed by EMSL user projects. In these collaborations, the technology drives the biology and the biology drives the technology by bringing together a community of diverse scientists,” says EMSL group leader for Functional and Systems Biology, Kristin Burnum-Johnson, who leverages EMSL’s omics suite to tackle key challenges in systems biology. “Scientists can leverage EMSL’s unique suite of proteomic and metabolomic capabilities with advanced imaging and computational approaches to answer precise biological questions.”

In other words, EMSL users can leverage a breadth of tools and expertise under one roof, rather than traveling to individual point sources of information and instrumentation. This is where that “biological motion picture” comes into play—by finding new and innovative ways to wed individual instruments and analytical techniques, EMSL can bring this capability to bear on the most challenging problems facing biological and environmental science.

Accessing EMSL’s omics capabilities

Scientists interested in bringing the power of EMSL’s omics suite to bear on their research can access these and additional resources through the EMSL User Program. There are currently three open calls for proposals—two through the Facilities Integrating Collaborations for User Science (FICUS) program, and one for Large-Scale Research (LSR).

Letters of intent for the FICUS call with the Atmospheric Radiation Measurement user facility and for the LSR calls are due February 8. Letters of intent for another FICUS proposal call with EMSL and the Joint Genome Institute are due March 7. The Molecular Observation Network (MONet), which aims to standardize molecular and microscale soil data across ecoregions in the United States, will be accepting another round of soil sampling proposals later this spring.

For additional information, check out the Biomolecular Pathways Integrated Research Platform page, or reach out to Mary Lipton.