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Systems Biology and Next Generation Technology

A Shift in Life Sciences from One to Many

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Systems Biology and Next Generation Technology

DNA Sequencing Flow Cell

NHGRI/NIH
Updated February 28, 2013

Next generation technology is a term that has been thrown around quite a bit in the biological sciences lately. Generally, of course, the term means new approaches that develop from current ones but offer fresh innovative perspectives or capabilities. However, in biotech, this term has come to be a shorthand way to refer to developments that expand a technology’s capabilities in a particular way—a way that encapsulates a recent major shift in life sciences research.

The Chemistry of Biology

Most biomedical research involves analysis of a diverse array of cellular components: nucleic acids, proteins, lipids, sugars, and other compounds. Each of these broad classes can also be further classified into smaller groups of molecules with unique characteristics (e.g., DNA, RNA, antibodies, glycoproteins, etc.), and so many approaches have been developed to analyze these chemical components of life that it is impossible for any individual, or even laboratory, to be versed in all of them. Each researcher really only uses a small set of techniques to study one particular process or aspect of a biological model.

Complex Chemical Interactions Produce Biology

However, living systems are not fragmented. The components all work together and responses emerge from this complex interaction. To really understand what’s happening in a cell or organism requires understanding what’s happening across the whole biological system, not just what’s going on with a single protein or gene. The chemistry of life is complex network and a new approach—systems biology—has developed specifically to investigate living systems from this perspective.

The data for this sort of systems-based analysis, however, is hard to come by using traditional biochemical assays or genetic techniques. Rather than looking at changes in one gene or protein at a time when some cells are treated with a drug, a systems approach requires looking at how a large number of genes, proteins, or other factors change together. Doing this requires ways to simultaneously assess the activation levels of thousands of genes, the activities of many proteins, or other broad-scale approaches that measure a whole class of molecules or components in the system at one time. The term next generation often serves as a shorthand way to refer to transforming and adapting old single component assays for this system-wide analysis.

New Tools for Analysis of Whole Systems

One of the first examples of system-wide analysis tools are DNA microarrays. Small bits of DNA affixed in a pattern to a solid glass slide enabled scientist to rapidly measure large number of genes simultaneously. Although not normally referred to as a next generation technology, these arrays provided massive amounts of data on which genes were active in various systems. Further, this technology developed in parallel with the sequencing of the human genome and really opened the door to systems-wide research.

The term next generation is most closely associated with DNA sequencing. Basic DNA sequencing technology has been around since the late 1970s. During the 1990s, though, with the human genome project—the push to fully sequence the entire complement of DNA in humans—there was a concerted effort to develop much more efficient approaches to sequence large numbers of DNA strands in parallel. Even after completion of the human genome in 2003, this trend continued so that we have reached a point where the whole human genome of an individual can be sequenced and analyzed in a few hours.

The Omics Take Over

With broad-based analysis of genes and DNA using microarrays and next generation sequencing, the field of genomics took hold. However, although genomics was the first area to benefit from broad based next generation assays, system-based approaches to analyze other cell components have produced a range of -omics studies. As I just discussed in a related article, proteomics has seen some real advances in the last few years as mass spectroscopy techniques to rapidly analyze proteins have become accessible. Also, techniques have developed to enable system-wide screening of various classes of other bio-molecules, such as metabolic intermediates (metabolomics) and miRNA.

A New Era in the Life Sciences

To reach a real understanding of complex biological processes, such as human development and disease progression, requires the development of a host of next generation technologies that enable measurement and comparison of many thousands of biological molecules in many thousands of model systems and conditions. The data these new technologies will generate is staggering, and will be impossible to handle without computational systems (which is a whole other discussion). However, it reflects the real complexity of living systems. After a few hundred years of working out bits and pieces of biology, the next generation of biotechnology may finally provide the tools to put together the complex puzzle of life.

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