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International Team Takes Aim at Large-scale Invertebrate Sequencing Project

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An actively growing consortium of researchers from around the world is gearing up to do coordinated genome sequencing on organisms from scantily studied invertebrate lineages, including marine invertebrates and other species outside of the insect and nematode worm groups.

The Global Invertebrate Genomics Alliance (GIGA) was motivated in part by the Genome 10K vertebrate sequencing project, coupled with an appreciation for the gap that exists between the genomic information being generated for vertebrate animals and the relative dearth of genomic representation from invertebrate creatures.

"The invertebrates actually have more species and are diverse in body plans and so on, so we thought the invertebrates needed a similar type of initiative," Nova Southeastern University researcher Jose Lopez told In Sequence.

He and other members of the GIGA research community penned a white paper in the January/February 2014 issue of Journal of Heredity introducing the rationale for, and feasibility of, developing a network of GIGA researchers to swap and analyze existing genome sequence data for many of the vertebrate lineages.

There, the team also considered the sorts of tools, technologies, and standardization needed to sequence thousands more invertebrates in future phases of the study, along with schemes for sharing and interpreting the massive amounts of sequence data such a study will generate.

"This is really just getting off the ground," Lopez said. "There are so many biologists who have been working on their respective study organisms for years. We hope this will be a clarion call, in some ways."

The 7,000 or so organisms earmarked for genome and/or transcriptome sequencing by GIGA include members of some three dozen invertebrate phyla, picked for their place in the animal tree and information their genomes may provide on everything from evolution and adaptation to developmental biology and ecology.

Since the effort is still in its early stages, more meetings will be needed to not only prioritize invertebrate taxa for the study, but also to continue hammering out the sample collection, sequencing, and analytical approaches for GIGA, according to Lopez.

GIGA organizers anticipate that that meeting, tentatively scheduled for late next year or early 2015, will also help attract new members who already have invertebrate genomic studies underway. A GIGA symposium is also planned for the Society for Molecular Biology and Evolution (SMBE) meeting in Puerto Rico in June 2014.

"We are definitely just at the very beginning this year," Lopez said. "We're going to see how the group develops."

At the moment, the GIGA effort and website mainly provide an opportunity for invertebrate researchers to share data and resources. In the coming years, the group hopes to generate additional genome sequence data and provide the opportunity for members to do comparative genomic analyses on such sequences.

"Right now, the website is kind of a gathering place," Lopez said. "We don't have funding to do analysis on the website, but it would be nice to have a functional browser, at some point, or a portal to higher analysis."

As the project takes shape, the existing GIGA website may morph into more of a functional genome browser, though Lopez noted that the sequencing, analysis, and computational goals of the project will ultimately depend on the funding that the project and its members bring in.

Consequently, the GIGA group is somewhat flexible with respect to the number of organisms to be sequenced and timeline for the project, which will likely continue evolving as new members come on board and additional sequencing and analysis tools become available.

"We hope to get a couple hundred [genomes] in the next few years, depending on the technology," Lopez said.

The past few years have seen pioneering studies on a few key invertebrates, Lopez noted, with genomes for corals, rotifers, and, most recently, a comb jelly, providing new clues about relationships within the animal tree.

Still, there have been fewer coordinated efforts to systematically characterize invertebrate genomes than there have been for their vertebrate cousins, with the exception of studies focused on model organisms — for instance, the 959 Nematode Genome effort — or insect sequencing studies such as the insect 5K initiative introduced in 2011.

That has left some branches of the invertebrate phylum less studied genomically, including the marine invertebrates, noted Lopez, whose own team is largely focused on understanding the organisms involved in coral reef building.

"There may not be as many species as there are for insects, but the phyla found in the ocean have interesting body plans that are not found in insects — so they warranted some kind of genome initiative," he said.

With that in mind, Lopez and his colleagues organized a workshop at NSU earlier this year, bringing invertebrates from several international locales to their south Florida campus.

That inaugural meeting, which was funded in part by the American Genetic Association, spawned the new white paper in the Journal of Heredity, a journal published by the AGA.

In addition to information on GIGA research issues related to sequencing policies and species selection, the white paper has a special focus on phylogeny, Lopez noted, in line with the group's interest in exploring invertebrate evolution through comparative genomics.

At this point, the consortium has a general target of sequencing some 7,000 non-insect and non-nematode organisms, though the precise species and taxa have not yet been selected.

For his part, Lopez would like to see the inclusion of invertebrate species involved in coral reef communities — including organisms living in coral reef crevices and surrounding sand — in the hopes that additional genomic information will aid efforts to preserve those threatened ecosystems.

Other aquatic environments have largely untapped invertebrate collections as well, he noted, including deep sea sites, mangroves, and estuaries.

"There is a whole lot of diversity that hasn't been catalogued," he said. "Part of this [project] is to help jumpstart that and advance a lot of these studies using genomics as a tool."

Beyond the biological information hidden in invertebrate genomes, those involved in the effort are also keeping potential food industry and human health applications in mind when selecting species for future study.

For example, the invertebrate world has been a long-time resource for researchers on the hunt for new natural products such as the anti-cancer compound identified in a mangrove sea squirt species called Ecteinascidia turbinata.

Ideally, investigators want to identify such compounds and untangle the genes and pathways behind them so that they can be produced without harvesting large numbers of source creatures.

"If we understand the genes and the pathways, then we could synthesize or begin the partial synthesis in the library," Lopez explained. "We don't have to go back and possibly decimate the population of an organism."

The first stage of GIGA will focus primarily on genome and transcriptome sequencing, with the possibility of expanding into epigenetic studies and other types of analysis in the future, if sufficient funding is available.

It remains to be seen whether funding for GIGA sequencing efforts will come primarily from individual member labs or whether the consortium itself can secure its own funding, but Lopez noted that the team will explore both approaches to secure financing for the project and may work with industry partners if such opportunities arise.

"Funding the sequencing of thousands of invertebrate genomes will require creative and collaborative approaches that go beyond the traditional funding mechanisms of individual principal investigator grants," the white paper authors noted.

"While the GIGA team has started exploring possible funding opportunities, we invite feedback and participation from the scientific community for joint fund-seeking strategies and ideas," they wrote.

The March workshop held in Florida included researchers from the US, China, and Europe and industry representatives from companies such as Life Technologies, Pacific Biosciences, and BioNanoGenomics.

The group has roughly doubled since that initial workshop and is continuing to seek new members, particularly those who have experience working with some of the rarer organisms from non-insect or –nematode groups.

"I'm looking forward to meeting a lot of other biologists who are studying a lot of this diversity from different angles and questions to see if we can apply genomics tools to that," Lopez said.

He expects early stages of the GIGA study to follow many of the sequencing and analytical approaches being developed by large vertebrate sequencing consortia, including Genome 10K.

As the program comes into its own, though, there may be opportunities for GIGA members to introduce their own innovations — for instance, for maximizing the information obtained from small and/or rare invertebrate samples, culturing organisms that are currently difficult to grow in the lab, or finding new ways to interpret patterns in the invertebrate genomes and transcriptomes.

"The invertebrates will have their own challenges, in terms of preparing samples, and they have large genomes also, some of them, so we have to take care of that as well," Lopez noted.

The sequencing technologies that will be used for the GIGA project are still up in the air. Genomes sequenced in the immediate future will likely include Illumina sequence data, Lopez said, though he noted that technologies for sequencing long fragment libraries may be of interest as well given the size of some of the invertebrate genomes.

According to the white paper, members of the GIGA effort plan to make sequence data available to other members of the research community in an open, transparent, and ongoing manner.

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