Emerging research fields look for early opportunities to make a dent in clinical applications

By Gary Tufel

In research labs around the world, scientists are pursuing studies in a variety of novel fields that promise to open new understandings of human health and disease. Building on and adding to the insights developed by the Human Genome Project, such “omics” fields also represent opportunities for creating advanced diagnostics that will meet the emerging needs of a healthcare sector focused on the pursuit of precision and personalized medicine.

Encouraging study results have also led to renewed interest among investors and strategic acquirers, who seem at last convinced of the collective potential of omics pursuits, both for diagnostic and therapeutic applications. “Moving forward, companies with clinical applications of omics technologies and with mature revenue streams continue to be possible mergers and acquisitions targets,” observed one report. “Firms operating in the next-generation sequencing space, as well as bioinformatics firms developing technologies to analyze and interpret omics data, also remain acquisition targets.”1

In this article, CLP looks at some of the key efforts contributing to the advance of omics research, and how a few notable field researchers and diagnostics companies are approaching the potential to develop diagnostic applications.


As distinguished from molecular biology and genetics, which emphasize the study of individual genes, “genomics” is focused on analyzing the structure and function of an organism’s genome—the complete DNA sequence that makes up the individual.2

Applied to healthcare, analyzing a person’s DNA sequence can provide a better understanding of their health risks, such as how susceptible a person is to a particular disease or whether the person might have an adverse reaction to a particular medication. Such analyses are expected to bring about both earlier interventions to prevent or delay the onset of disease, and more precise therapies when medical interventions are necessary. By aggregating genomic data across large populations, public health officials can more effectively address health concerns, reducing healthcare costs and improving quality of life.

The field of genomics is currently dominated by academic and other research organizations whose focus is on creating understandings that will support the development of future genome-based therapies. But already, the potential of genomics has captured the attention of healthcare providers and payors, and companies in the field are working to define projects that will lead to early application of discoveries in genomics.

In January of this year, Lockheed Martin, Bethesda, Md, and Illumina Inc, San Diego, announced a strategic alliance to collaborate on scalable and affordable genomics solutions to provide personalized healthcare for national populations. The alliance brings together Illumina’s next-generation sequencing (NGS) tools with Lockheed Martin’s expertise in large-scale information systems and integration to meet the needs of countries as they begin to integrate genomics into their national health systems.3

Horace Blackman, Lockheed Martin.

Horace Blackman, Lockheed Martin.

“Genomics is enabling a fundamental transformation of healthcare,” says Horace Blackman, vice president of health and life sciences for Lockheed Martin’s information systems and global solutions business. “We envision the advantages of early national adoption for countries across the globe, applying clinical decision support applications that can improve health and healthcare, and lower national healthcare costs.”

“Over the past 15 years, scientific understanding of the human genome and its role in disease has exploded, prompting a revolution in healthcare,” says Charles ‘Buck’ Strom, MD, PhD, FAAP, FACMG, HCLD, vice president for genetics and genomics at Quest Diagnostics, Madison, NJ. “Where once patients were cared for all the same, now we can diagnose, treat, and monitor disease for the individual, thanks to insights provided by genomic testing.”

 Charles ‘Buck’ Strom, MD, PhD, Quest Diagnostics.

Charles ‘Buck’ Strom, MD, PhD, Quest Diagnostics.

Securing advances in genomics that can be applied to everyday clinical applications requires a commitment to new diagnostic technologies. “Building on our long-standing leadership in genomics, Quest Diagnostics is making significant investments in novel and established technologies to improve analysis of the genome not only to aid the diagnosis of diseases like cancer and neurological disorders but also to improve treatment selection and monitoring,” says Strom. “We are particularly excited about the potential of molecular combing, a proprietary technique Quest offers through an exclusive US license, because it affords the potential to identify large gene rearrangements other methods can miss.”

But for all its promise, says Strom, genomic analysis also has a potential dark side: the potential to yield information that is not definitive or actionable. For this reason, Quest Diagnostics and the French Institute of Health and Medical Research (INSERM) have partnered to created BRCA Share, a service that provides access to research findings and clinical test data for BRCA 1 and BRCA 2, two genes implicated in inherited risk for breast, ovarian, and other cancers.

Because of gaps in knowledge about gene variants of unknown significance, says Strom, too many people receive BRCA test results that do not clearly indicate cancer risk. “By sharing highly curated BRCA data, we hope to shed new insights into the role of BRCA genes on cancer risk. In doing so, we expect to have a significant favorable impact on cancer care, not only in the United States but globally.”

Genomic analysis continues to move from research labs to common practice in clinical laboratories in the form of molecular diagnostics, says Barney Saunders, PhD, senior vice president for sales and marketing at NanoString, Seattle. “However, these diagnostics can take different forms. Most of the genomic molecular diagnostic products available to date are based on the analysis of DNA sequences and the identification of actionable sequence variants,” says Saunders, “and very few of these diagnostics go beyond sequence analysis to the gene expression domain.”

The Nanostring nCounter Dx analysis system encompasses a prep station (left) and digital analyzer.

The NanoString nCounter Dx analysis system encompasses a prep station (left) and digital analyzer.

NanoString has filled this void, says Saunders, with its nCounter Dx analysis system, which is capable of measuring the level of gene expression based on up to 800 different mRNA targets, simultaneously, from a tiny tissue sample in a single tube. The system can also be targeted at miRNA expression, copy number variations, and gene fusions.

FDA cleared the nCounter Dx analysis system in September 2013, together with NanoString’s Prosigna breast cancer assay. Prosigna enables clinical laboratories to provide prognostic testing for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) early-stage breast cancer patients that previously could only be obtained through a centralized laboratory.

“Based on the PAM50 gene set, Prosigna measures the expression of 50 genes and applies a complex algorithm to assess the risk that the patient’s cancer will recur within 10 years,” says Saunders. “The result is provided to the physician in an easy-to-read report indicating low, intermediate, or high risk and a continuous risk-of-recurrence score (Prosigna score) from zero to 100 that is correlated to the probability of distant recurrence over a 10-year period.”

“NanoString’s nCounter technology is also used in laboratory-developed tests based on an open chemistry called Elements,” says Saunders. “Elements reagents can be used to quantify mRNA copy number variations and gene fusions as part of molecular diagnostic tests developed by individual high-complexity clinical laboratories.”

The GemCode molecular barcoding and analysis system by 10X Genomics.

The GemCode molecular barcoding and analysis system by 10X Genomics.

10X Genomics, Pleasanton, Calif, is seeking to advance the field of genetic sequencing by providing an innovative genomics platform that upgrades the capabilities of existing short-read sequencers. The company’s GemCode platform is a unique molecular barcoding and analysis system that consists of instrumentation, reagents, and software. Using an elegant combination of microfluidics, chemistry, and bioinformatics, the system makes it possible for researchers to identify structural variants, haplotype phasing, and other valuable long-range genomic information, while leveraging existing sequencing workflows.

The GemCode Platform generates a powerful new type of genomic data: linked reads. The platform partitions arbitrarily long DNA molecules (including >100kb) and prepares sequencing libraries in parallel, so that all fragments produced within a partition share a common barcode. A simple workflow combines large partition numbers with a massively diverse barcode library to generate >100,000 barcode-containing partitions, while requiring a sample of only ~1ng of DNA.

“10X Genomics is enabling researchers to routinely access genomic information that was previously difficult or impossible to obtain,” says Serge Saxonov, CEO of 10X Genomics.


Jose Castro-Perez, Waters Corp.

Jose Castro-Perez, Waters Corp.

“Alterations in lipid profiles are associated with a variety of metabolic diseases, including obesity, heart disease, and diabetes,” says Jose Castro-Perez, MSc, PhD, director of health sciences business operations at Waters Corp, Milford, Mass. “Lipidomics has become a powerful research tool for investigating the mechanisms of action for different disease modalities.”

In association with human genetics, says Castro-Perez, lipidomics plays a significant role in the discovery of new therapeutic biological targets as well as related biomarkers that represent a disease state and can be utilized to track disease progression and regression. “Liquid chromatography coupled with mass spectrometry (LC-MS) creates a powerful tool for the identification of these novel lipid biomarkers, enabling researchers to understand their underlying biology and subsequently address unmet medical needs,” he says.

The Synapt G2-Si mass spectrometer by Waters performs quadrupole time-of-flight mass spectrometry with ion mobility separations.

The Synapt G2-Si mass spectrometer by Waters performs quadrupole time-of-flight mass spectrometry with ion mobility separations.

“In particular, quadrupole time-of-flight mass spectrometry (Q-TOF MS) with ion mobility separations (IMS)—as offered by the Waters Synapt G2-Si system—provides unique capabilities for identifying, characterizing, and quantifying low-level lipid species with greater clarity and definition than ever before,” says Castro-Perez. “For clinical research laboratories, such analytical technologies offer a transformative opportunity to replace aging techniques such as immunological, radioactive, fluorometric, and colorimetric assays.”

“Waters is at the forefront of technical innovation, and our goal is to make these LC-MS and IMS technologies more accessible to clinical researchers,” says Castro-Perez. “From lipids to biomarkers with the aim of improving quality of life, LC and MS are the most effective analytical technologies across the health sciences continuum.”


Sometimes called “expression profiling,” “transcriptomics” is the study of the transcriptome—the complete set of RNA transcripts that exists in a specified cell population under various conditions. Clinical researchers are studying the transcriptomes of cancer cells to understand the processes that lead to the development of various kinds of cancer. Transcriptomic studies have also been performed to examine the underlying mechanisms of adverse drug reactions, an understanding of which is critical for developing clinical diagnosis and management strategies.4

By sequencing reverse-transcribed complementary DNA fragments (cDNA) from isolated RNA, researchers are able to interrogate the broad range of transcripts differentially expressed across cell states. A variety of approaches are used to achieve broad-scale sequencing of RNA transcripts, and are collectively referred to as “RNA-seq.” Variations on these approaches are aimed at capturing RNA transcripts derived from increasingly minute cellular material, depleting and controlling levels of coding and non-coding RNA, and ensuring strand specificity of sequenced cDNA fragments.

One of the key challenges to designing RNA sequencing experiments is choosing the sample preparation approach that provides the most useful data to answer the biological question. These include

  • Isolation and qualification of nucleic acids.
  • Automated cDNA synthesis and library preparation.
    • Illumina TruSeq RNA.
    • NuGen Ovation RNA-seq system V2, separation of pre- and post-PCR processes.
  • Quality control checkpoints for RNA quantification, size, and integrity.
  • Analysis of sequence data.


In the field of study known as “epigenomics,” researchers are trying to chart the locations and understand the functions of all the chemical tags that mark the genome.

Until recently, scientists thought that human diseases were caused mainly by changes in DNA sequence, infectious agents such as bacteria and viruses, or environmental agents. Now, however, researchers have demonstrated that changes in the epigenome—the multitude of chemical compounds that can tell the genome what to do—can also cause, or result from, disease. Epigenomics has thus become a vital part of efforts to better understand the human body and to improve human health. Epigenomic maps may someday help doctors to determine an individual’s health status and tailor a patient’s response to therapies.

The epigenome is made up of chemical compounds and proteins that can attach to DNA and direct such actions as turning genes on or off, controlling the production of proteins in particular cells. When epigenomic compounds attach to DNA and modify its function, they are said to have “marked” the genome. These marks do not change the sequence of the DNA. Rather, they change the way cells use the DNA’s instructions. The marks are sometimes passed on from cell to cell as cells divide. They can also be passed down from one generation to the next.5

As part of the encyclopedia of DNA elements (ENCODE) project—which aims to catalog the working parts of the genome—the National Human Genome Research Institute is funding researchers to make epigenomic maps of various cell types. Other investigators supported by the National Institutes of Health (NIH) have developed a number of epigenomic maps from several human organs and tissues. These NIH projects are part of an international effort to understand how epigenomics could lead to better prevention, diagnosis, and treatment of disease.

For Epigenomics AG, a molecular diagnostics company based in Berlin, Germany, the key epigenomic activity of interest is DNA methylation, which influences the correct expression of many genes and gene sequences. Based on the understanding that “every cell type has a unique DNA methylation fingerprint that changes during normal biological processes and many diseases—in particular cancer”—the company is developing and commercializing a pipeline of proprietary products for the screening and diagnosis of cancer.

Its products enable doctors to diagnose cancer earlier and more accurately, leading to improved outcomes for patients. Its lead product, Epi proColon, is a blood-based test for the early detection of colorectal cancer, which is currently marketed in Europe and is in development for the United States.


“Metabolomics” aims to compare the relative differences between biological samples based on their metabolite profiles. It can provide an instantaneous snapshot of the entire physiology of an organism. Because of the diverse requirements of the systems studied, the chemical diversity of metabolites, and their wide variation in abundance, metabolomics research usually requires multiple techniques.6

Agilent Technologies, Santa Clara, Calif, says researchers are using metabolomics approaches to study issues in a wide range of areas, including disease research, toxicology, environmental analysis, agriculture, biofuel development, and nutrition. Metabolomics results can also be combined with gene expression or proteomics studies to provide a richer and more comprehensive understanding of the biology. Agilent metabolomics solutions are designed to address two major approaches:

  • Discovery metabolomics involves acquisition of data in an untargeted mode, in which all metabolites are detected to determine those that are significantly different between experimental and control conditions. Agilent has developed sophisticated tools for untargeted or “targeted” data mining, and these metabolites are annotated and identified using Agilent’s custom metabolite databases and spectral libraries. The identified metabolites are then mapped onto biological pathways.7
  • Quantitative metabolomics is hypothesis driven. It may be used to confirm results from a previous discovery-based metabolomic profiling experiment or based on results from a genomics and/or proteomics study. Typically a large number of samples is needed to validate a few targets and has the advantage of absolute quantitation using analytical standards.8


“Proteomics” is the systematic study of proteins on a large scale, with particular emphasis on their functions and structures. Proteomics has the potential to answer key questions not addressed by genomics studies, because proteins are the functional units of cells. Proteomics research is enhanced by both protein and DNA sequence databases, advances in mass spectrometry, and the development of computer algorithms for database searching. The most common application of proteomics is the analysis of target proteins.

Personalized medicines are developed according to the genetic make-up of an individual, and today are extensively used for treatment of diabetes and cancer. An increase in demand for personalized medicines is one of the major contributors to the growth of the market for proteomics goods and services. Analysts expect that the global market in proteomics will grow at a compound annual growth rate of 8.39% over the period from 2014 to 2019.9

New England Peptide Inc (NEP), Gardner, Mass, is a producer of mass spectrometry peptide standards for biomarker discovery, and offers a new product line called Tryptides, or isotope-labeled tryptic peptide fragments. Launched in cooperation with investigators from the clinical proteomic tumor analysis consortium (CPTAC) and others, the product line spans over 1000 proteins of interest.10

Amanda Paulovich, MD, PhD, Fred Hutchinson Cancer Research Center.

Amanda Paulovich, MD, PhD, Fred Hutchinson Cancer Research Center.

Many of these peptides have been characterized by CPTAC investigators as part of the consortium’s assay development working group.11 “The mission of the working group is to disseminate highly characterized, targeted proteomic assays to the community to standardize protein measurements and harmonize results across the community,” says Amanda Paulovich, MD, PhD, associate professor of oncology at the Fred Hutchinson Cancer Research Center, and chair of the CPTAC working group. “Indeed, we have developed the assay portal to accomplish this goal. We are excited to work with NEP to provide the community with access to high quality, affordable peptide standards, the availability of which is critical to our mission.”

Sam Massoni, New England Peptide.

Sam Massoni, New England Peptide.

“We have been honored to work with investigators in the CPTAC assay group in a wide array of projects,” says Sam Massoni, CEO of NEP. “The consortium is well respected, very collaborative, and involves many of the thought leaders in the mass spectrometry field. Offering some of their designed peptide standards, along with those developed at NEP and with other investigators, is the next logical step, as we believe the key to any good MS assay is having high quality, accurately quantitated peptide standards.”


These are still early days for the development of diagnostic technologies based on omics research. In coming years, developers will be challenged to produce results that are both early enough and accurate enough to demonstrate the clinical utility of such tests. Such demonstrations will be needed to achieve adoption of the tests by healthcare providers and reimbursement coverage of the tests by third-party payors.

The future market for omics diagnostics will no doubt be global in scope, increasing the need for harmonized protocols and standardized metrics across laboratories and methodologies. The ability of labs to provide reproducible results on standard equipment, using techniques with little protocol variation, will also be important.

Gary Tufel is a contributing writer for CLP. For more information contact CLP chief editor Steve Halasey via [email protected].


  1. Sharp uptick in M&A in omics life science tools/MDx space seen in first half of 2015. GenomeWeb. June 26, 2015.
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  1. Cui Y, Paules RS. Use of transcriptomics in understanding mechanisms of drug-induced toxicity. Pharmacogenomics. 2010;11(4):573–585; doi: 10.2217/pgs.10.37.
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  1. Quantitative metabolomics. [online briefing.] Santa Clara, Calif: Agilent Technologies, 2015. Available at: http://metabolomics.chem.agilent.com/Practical-Guide-to-Metabolomics/123341-Quantitative-Metabolomics. Accessed June 29, 2015.
  1. Global Proteomics Market, 2015–2019. London: Technavio, 2015.
  1. Clinical proteomic tumor analysis consortium. [Program description online.] Bethesda, Md: National Cancer Institute, 2015. Available at: http://proteomics.cancer.gov/programs/cptacnetwork. Accessed July 5, 2015.
  1. Office of cancer clinical proteomics research, assay portal. [Online.] Bethesda, Md: National Cancer Institute, 2015. Available at https://assays.cancer.gov. Accessed July 5, 2015.