Back at JCVI's Rockville, Maryland laboratory, researchers from the voyage extracted DNA from the microbial cell and viral particle in samples and sequenced this information using a combination of technologies. What emerged were several billion pieces of DNA representing an ecosystem that scientists know very little about.
This approach to biology is called metagenomics and it represents the next frontier of genetic and microbial ecology research. According to a 2011 study, 85 percent of the world's organisms are unnamed and unknown. This "dark matter of life" - organisms that resist culturing and traditional sequencing methods - is all around us. Though difficult to uncover, these organisms play a critical role in our lives.
"Microbes run the world. It's that simple", wrote the authors of the 2007 National Academies releaseThe New Science of Metagenomics. "Although we can't usually see them, microbes are essential for every part of human life - indeed all life on Earth. Every process in the biosphere is touched by the seemingly endless capacity of microbes to transform the world around them."
Until now, almost all of our knowledge of microbes came from the laboratory, where microbes are raised in unnatural circumstances without ecological context. "The science of metagenomics, only a few years old, will make it possible to investigate microbes in their natural environments, the complex communities in which they normally live", the report continued. "It will bring about a transformation in biology, medicine, ecology, and biotechnology that may be as profound as that initiated by the invention of the microscope."
Like trying to solve a jigsaw puzzle without the picture on the box and many missing pieces, the researchers set about reconstructing the larger biome they had sampled in the ocean.
Reporting in the October 2012 edition ofPLOS One, researchers from JCVI described the method by which they analyzed the samples to determine the bacterial and viral diversity of the Indian Ocean and the relationships among organisms. It was the first study to holistically explore the dynamics of aquatic viruses across multiple size classes and provided unprecedented insight into virus diversity, metabolic potential, and virus-host interactions in the region.
One of the authors of thePLOS Onepaper, Andrey Tovchigrechko, a research scientist at JCVI, developed the software that organizes and draws insights from the fragments of DNA extracted from the oceans. Running on the Ranger supercomputer at the Texas Advanced Computing Center (TACC), the researchers gleaned information about this oceanic ecosystem that would be impossible to gather without massive computational power, including biodiversity data that will be useful in tracking the impact of climate change on ocean life.
"With metagenomics, you take a sample of the environment and slice all the DNA that's present into small pieces", explained Anrey Tovchigrechko. "You don't have to culture. That's a big advantage because nobody knows how to culture most of the organisms that are out there. The downside is that you get a mix of organisms and you have to sort it out. That's what most of the bioinformatics activities related to metagenomics deal with."
"Metagenomics is a data-intensive research area", stated fellow JCVI researcher and associate professor, Shibu Yooseph. "We take this culture-independent approach to studying microbial communities, and the result is that most of the complexity in making inferences has been transferred to the computational end of things. TACC's resources are incredibly useful in addressing the throughput computing requirements in this field."
Trailblazing science needs innovative computer programmers to create the tools that can turn an ocean of genomic information into useful information. For the metagenomic study of the Indian Ocean, Andrey Tovchigrechko and his colleagues used MGTAXA, one of the tools Andrey Tovchigrechko created, to ascertain the relationship between viruses and bacteria in the Indian Ocean study.
Many viruses insert themselves for some time into the host genome and lie dormant, and that class of viruses tends to adopt the DNA composition of a host. "The tool was implemented with a novel method to predict what the bacterial hosts might be, based on certain viral sequences", Andrey Tovchigrechko stated.
Using MGTAXA helped them develop hypotheses about the relative abundance of various microbes with more precision, and identify types of bacteria that would have been difficult to isolate otherwise.
MGTAXA and the other software tools developed at JCVI apply equally well to the microbial communities present in and on our body, the so-called microbiome.
In a study funded by the National Institutes of Health and jointly led by Zhiheng Pei (NYU) and Karen Nelson (JCVI), Andrey Tovchigrechko, Shibu Yooseph and others are applying a metagenomic approach to the human esophagus and the microbial imbalances there that may play a role in certain kinds of gastric acid reflux and esophageal adenocarcinoma, a form of cancer.
Their recent study analyzed the esophageal environment of more than 50 subjects, representing both healthy individuals and those at various stages of the disease. Though not enough is known about the dynamics of disease and the microbiome, evidence suggests a relationship between the two.
Studies like these, driven by creative algorithms and powered by supercomputers, provide evidence, promote the creation of new treatment options, and help develop the methods and work flows required for further analysis.
"A lot of this is our initial effort to understand the microbiome", Shibu Yooseph stated, "but ultimately, we want to be at a stage where we can identify biomarkers, either organisms or gene products, that could be the triggers for some of these diseases, or use those markers as diagnostics to identify the disease status."
From single genes to the human genome, and from discrete organisms to ecological niches, genetics continues to evolve as a field, providing new useful information about the broader world around us.
"There's so much uncharacterized diversity in the microbial realm that we're still trying to understand using metagenomics", Shibu Yooseph stated. "From human health to bioenergy alternatives, understanding these microbial systems would have an immediate impact on society."