Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Seeking structure with metagenome sequences

20.01.2017

Metagenomics database helps fill in 10 percent of previously unknown protein structures

For proteins, appearance matters. These important molecules largely form a cell's structures and carry out its functions: proteins control growth and influence mobility, serve as catalysts, and transport or store other molecules. Comprised of long amino acid chains, the one-dimensional amino acid sequence may seem meaningless on paper. Yet when viewed in three dimensions, researchers can see what a protein's structure is and how a protein's structure, and particularly the way it folds, determines its functions.


In a study published Jan. 20, 2017 in Science, a team led by University of Washington researchers and including DOE JGI researchers reports that structural models have been generated for 12 percent of the protein families that had previously had no structural information available. This is a brief overview of the work. Top: Researchers gathering samples from Great Boiling Spring in Nevada. Left: a snapshot of aligned metagenomic sequences. Each row is a different sequence (the different colors are the different amino acid groups). Each position (or column) is compared to all other positions to detect patterns of co-evolution. Bottom: the strength of the top co-evolving residues is shown as blue dots, these are also shown as colored lines on the structure above. The goal is to make a structure that makes as many of these contacts as possible. Right: a cartoon of the protein structure predicted. The protein domain shown is from Pfam DUF3794, this domain is part of a Spore coat assembly protein SafA.

Image of Great Boiling Spring by Brian Hedlund, UNLV. Protein structure and composite image by Sergey Ovchinnikov, UW

There are close to 15,000 protein families - groups of families that share an evolutionary origin - in the database Pfam. For nearly a third (4,752) of these protein families, there is at least one protein in each family that already has an experimentally determined structure. For another third (4,886) of the protein families, comparative models could be built with some degree of confidence. For the final third (5,211) of the protein families in the database, however, no structural information exists.

In the January 20, 2017 issue of Science, a team led by University of Washington's David Baker in collaboration with researchers at the U.S. Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science User Facility, reports that structural models have been generated for 614 or 12 percent of the protein families that had previously had no structural information available.

"That this could be accomplished using computational modeling methods was not at all apparent 5 years ago," the team noted in their paper. This accomplishment was made possible through a collaboration in which the Baker lab's protein structure prediction server Rosetta analyzed the metagenomic sequences publicly available on the Integrated Microbial Genomes (IMG) system run by the DOE JGI.

"A large number of protein families (in Pfam) have low number of sequences," said study first author Sergey Ovchinnikov, a graduate student in the Baker lab. "This resulted in two consequences: 1) nobody cared about these families (since they were small); and, 2) co-evolution methods could not be applied to study them. With metagenomics, we found that some of these neglected families with only a handful of sequences so far, can now become as large as some of the most studied ones, when metagenomics data are taken into account! Moreover, we can offer a 3D model of a representative sequence from the family. We hope this will spark interest in some of these families."

Armed with genome sequences, researchers like Baker have been able to identify sets of amino acids that evolve simultaneously, even though they are nowhere near each other on the unfolded chain. Such events suggests these amino acids are neighbors in the folded protein, offering researchers hints as to the protein's structure. Structural proximity can suggest a functional relationship and thus natural selection, acting on the function, can favor not just one amino acid but all that are in the set.

Nikos Kyrpides, DOE JGI Prokaryote Super Program head, said the collaboration between the Baker lab and the DOE JGI allowed the team to come up with a powerful way of predicting structures and structural alignments. "Such efforts, were previously restricted on protein families generated from sequences found on the isolate genome only. These genomes comprise about 200 million sequences. As expected, when we added on those our metagenomics data, harnessing the 5 billion assembled metagenome sequences available on our IMG/M database, we were able to dramatically increase the coverage of many of the known protein families. Efforts like this one heavily depend on the availability of assembled metagenomics sequences, which is an advantage the DOE JGI brings to the table with our high quality assemblies."

Kyrpides added that this work, which also involved DOE JGI researchers Neha Varghese and George Pavlopoulos, embodies another kind of collaboration that he'd like to see encouraged. "People came to us because we are maintaining the largest integration of assembled metagenomes. The application of such tools on our data provides a great example of how the larger community can utilize JGI resources for discovery. We would very much like to see more success stories like this one through a new Data Science call between the JGI and the National Energy Research Scientific Computing Center (NERSC)."

The JGI-NERSC Microbiome Data Science call will enable users to perform state-of-the-art computational genomics and metagenomics research and help them translate sequence information, generated by the DOE JGI or elsewhere, into biological discovery. This proposal call builds upon the success of "Facilities Integrating Collaborations for User Science" (FICUS) initiative, established to encourage and enable researchers to more easily integrate the expertise and capabilities of multiple national user facilities into their research. Applications for JGI-NERSC collaborative science call are currently being accepted until March 1, 2017. For more information about the call, go to: http://jgi.doe.gov/user-program-info/community-science-program/how-to-propose-a-csp-project/ficus-jgi-nersc/.

###

The U.S. Department of Energy Joint Genome Institute, a DOE Office of Science User Facility at Lawrence Berkeley National Laboratory, is committed to advancing genomics in support of DOE missions related to clean energy generation and environmental characterization and cleanup. DOE JGI, headquartered in Walnut Creek, Calif., provides integrated high-throughput sequencing and computational analysis that enable systems-based scientific approaches to these challenges. Follow @doe_jgi on Twitter.

DOE's Office of Science is the largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

Massie Ballon | EurekAlert!

Further reports about: Genome amino acid metagenome metagenome sequences sequences

More articles from Life Sciences:

nachricht At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History

nachricht New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>