The Nature TOC-email arrived yesterday, and they have a whole “insight” section on microbial oceanography! Four years ago, Nature Reviews Microbiology had a special issue with a few papers about it, two years ago PLoS Biology presented their Oceanic Metagenomics Collection, and now then the Nature supplement. Why would a computer scientist like me care? Well, my first study was in microbiology, and they have scaled up things a lot in the meantime, thereby making computers indispensible in their research. For those unfamiliar with the topic, you can get an idea about early computational issues in my previous post and comments by visitors, but there are new ones that I’ll mention below.

Although the webpage of the supplement says that the editorial is “free access”, it is not (as of 14-5 about 6pm CET and today 9am). None of the 5 papers—1 commentary and 4 review papers—indicate anything about the computational challenges: “the life of diatoms in the world’s oceans”, “microbial community structure and its functional implications”, “the microbial ocean from genomes to biomes”, and “viruses manipulate the marine environment”. Given that DeLong’s paper of 4 years ago [1] interested me, I chose his review paper in this collection [2] to see what advances have been made in the meantime (and that article is freely available).

One of the issues mentioned in 2007 was the sequencing and cleaning up noisy data in the database, which now seems to be much less of a problem, even largely solved, so the goal posts start moving to issues with the real data analysis. With my computing-glasses on, Box 2 mentions (my emphases underlined and summarised afterwards):

Statistical approaches for the comparison of metagenomic data sets have only recently been applied, so their development is at an early stage. The size of the data sets, their heterogeneity and a lack of standardization for both metadata and gene descriptive data continue to present significant challenges for comparative analyses … It will be interesting to learn the sensitivity limits of such approaches, along more fine-scale taxonomic, spatial and temporal microbial community gradients, for example in the differences between the microbiomes of human individuals44. As the availability of data sets and comparable metadata fields continues to improve, quantitative statistical metagenomic comparisons are likely to increase in their utility and resolving power. (p202)

Let me summarise that: DeLong asserts they need (i) metadata annotations as a prerequisite for statistical approaches; (ii) deal with temporal data, and (iii) deal with spatial data. There is a lot of research and prototyping going on in topics ii and iii, and there are few commercial industry-grade plugins, such as the Oracle Cartridge, that do something with the spatial data representation. Perhaps that is not enough or it is not what the users are looking for; if this is the case, maybe they can be a bit more precise on what they want?

Point i is quite interesting, because it basically reiterates that ontologies are a means to an end and asserts that statistics cannot do it with number crunching alone but needs structured qualitative information to obtain better results. The latter is quite a challenge—probably technically doable, but there are few people who are well versed in the combination of qualitative and quantitative analysis. Curiously, only MIAME and the MGED website are mentioned for metadata annotation, even though they are limited in scope with respect to the subject domain ontologies and ontology-like artefacts (e.g., the GO, BioPax, KEGG), which are also used for annotation but not mentioned at all. The former deal with sequencing annotation following the methodological aspects of the investigation, whereas the latter type of annotations can be done with domain ontologies, i.e. annotating data with what kind of things you have found (which genes and their function, which metabolism, what role does the organism have in the community etc.) that are also need to carry out the desired comparative analyses.

There is also more generic hand-waiving that something new is needed for data analysis:

The associated bioinformatic analyses are useful for generating new hypotheses, but other methods are required to test and verify in silico hypotheses and conclusions in the real world. It is a long way from simply describing the naturally occurring microbial ‘parts list’ to understanding the functional properties, multi-scalar responses and interdependencies that connect microbial and abiotic ecosystem processes. New methods will be required to expand our understanding of how the microbial parts list ties in with microbial ecosystem dynamics. (p203)

Point taken. And if that was not enough,

Molecular data sets are often gathered in massively parallel ways, but acquiring equivalently dense physiological and biogeochemical process data54 is not currently as feasible. This ‘impedance mismatch’ (the inability of one system to accommodate input from another system’s output) is one of the larger hurdles that must be overcome in the quest for more realistic integrative analyses that interrelate data sets spanning from genomes to biomes.

I fancy the thought that my granularity might be able to contribute to the solution, but that is not yet anywhere close to user-level software application stage.

At the end of the paper, I am still—as in 2005 and 2007—left with the impression that more data is being generated in the whole metagenomics endeavour than that there are computational tools to analyse them to squeeze out all the information that is ‘locked up’ in the pile of data.

References

[1] DeLong, E.F. Microbial community genomics in the ocean. Nature Reviews Microbiology, 2005, 3:459-469.

[2] DeLong, E.F. The microbial ocean from genomes to biomes. Nature, 2009, 459: 200-206.

Cameron Currie Ancient mutualism for fungi and ants – something I love to learn more about.  Great system for mutualism of animals and microbes. Showing Chapela et al figure of co-evolution.

There is also a parasite that specializes on the ant-fungal interaction. Escovopsisco-evolves with ant and fungus. So a triparte symbiosis. But Wait. The he introduces the 4th player, where the actinobacter which produces antibiotics to protect the ants. Specialized organs for culturing the bacteria which are all over the body which are specialized opening for crypts for the filamentous bacteria. 6-8 years ago, 4-way interactions.

Work in the GLBRC is currently to understanding of the breakdown of the plant biomass. The fungus that is cultured by the ants is not cellulosic. Mature colonies can produce huge amounts of biomass but it gets broken down. See if cellulose is decomposed in the fungus garden, and is being broken down. Lignin is not really getting destroyed though?

Project with the JGI is “Fungus Garden Metagenomics”. 16S metagenome. 400M bp from community sequencing. Interesting bacteria found in the fungal garden. lots of species from the gardens “Cellulomonas” sounds like it could be good hit… =)

The top hit is Klebsiella an N-fixer, cellulose-degrader and is a Gamma-proteobacteria. Gamma show up in general a lot in the top 20 hits.

What kind of enzymes are present? Beta-1,4-endoglucanase. Found several cellulase enzymes present in the garden that are of fungal origin so maybe the genes are only being expressed in the garden/dump.

Video of 10,000s of worker ants dumping the plant material dropping material into these huge dumps. The mounds have stratification as material is dumped at the top and ages and decomposes. Cellulose content at the top and bottom of dump is correlated with age, so the bottom has least amount of cellulose.

Diversity of leaf cutting ants – 210 lineages of fungus growing ant. Most are not leaf cutters. So there are different microbial associations with the different groups that should be determined.

Insect-fungal mutualisms are not unique to ants. Fungus-growing termites. May have cellulosic capabilities. Beetles and yeasts, where the beetles spread the yeast (these I presume would be Ceratocystis and Ophiostoma).

How much of the leaf material brings in the microbial community. The ants groom the leaves to remove contaminants (like spores) which directs the community composition. I wonder how many plant endophytic fungi might still come in?

Bacteria in the farm may actually induce the fungal production of cellulosic enzymes. 10k 18S sequences from different strata.

http://www.nap.edu/catalog.php?record_id=11902

From the name it has something to do with the genome … or genetics. It’s a new, coined word that refers to the analysis of the genetics of many organisms together at the same time. So what is this? And why would I care?

About 2-1/2 years ago I discovered that genetics is cool … duh! Well, better late than never. In spite of love of computing it had never sunk in to me that the genome of any plant or animal is a program running inside a computer. And the computer is the living organism.

Why would I care about microbial communities? Except for viruses they are the most abundant life on Earth and have an overwhelming effect on our environment and our lives. Consider that about half the carbon dioxide on Earth is processed through microbes that live in the oceans. Then consider that the most modern climate models of ocean life include just five organisms. This is despite recent findings that point to thousands of species, which do many different things and presumably influence our climate.

Since most of these organisms physically look alike how would you ever tell them apart? … or determine what they do? This is now being done through their DNA. There is a revolution going on out there in analyzing DNA that is the equivalent of the twentieth century computer revolution. The new DNA sequencing technologies are producing data faster and cheaper each year and are overwhelming the computers and programs that can process it. There is even talk of each of us having our complete DNA sequence available as part of our medical record for a couple hundred dollars! But this does no one any good if we can’t read and understand the program … remember? DNA is the program of life. What does it say? How does it make the computing machinery of microbes live? And then what do those microbes do to the environment?

Complete DNA sequences of thousands of organisms are piling up in databases because of these new DNA sequencing machines. Most of this remains unanalyzed for several reasons. We don’t yet know the right biological questions to ask. We don’t have all the clever programs that would actually ask these questions of the computer. And there is now so much data that many questions totally overwhelm even existing supercomputers.

Sounds bad, huh? An opportunity missed? Absolutely not! This is a special time in science history … a convergence of events that bodes great opportunity for those who dare to jump on it. High performance computing expertise abounds from the twentieth century developments in the “hard” sciences and engineering. The revolution in DNA sequencing is offering a new opportunity to apply this expertise. And it’s in an field that is of such importance to society.

This is really exciting and I’m having a great time stepping across this boundary … working with sequences of DNA to sort out questions of who those microbes are and what do they do. Metagenomics.

The human body is home to a diverse range of microorganisms, estimated to outnumber human cells in a healthy adult by ten fold. The importance of characterizing human microbiota for understanding health and disease is highlighted by the recent launch of the Human Microbiome Project by the National Institutes of Health. This report, published online in Genome Research (http://www.genome.org/), describes the investigation of healthy human skin for microbiota diversity and establishes the basis for determining a core microbiome.

The Human Microbiome Project aims to characterize the microbial communities of several regions of the body, including skin, where determining the core microbiome is essential to understanding and developing new treatments for skin conditions and diseases such as acne and atopic dermatitis (eczema). In this study, researchers led by Dr. Julie Segre of the National Human Genome Research Institute have generated a diversity profile of human skin microbiota by sequencing 16S rRNA, a component of the prokaryotic ribosome, isolated from a specific region of skin. “We focused this study on the inner elbow to inform future clinical studies of the extremely common inflammatory skin disorder atopic dermatitis, which affects this area of the skin and is associated with Staphylococcus infections,” explains Segre.

The researchers find that in the healthy subjects tested, Proteobacteria (predominantly Pseudomonas and Janthinobacterium) constituted the majority of inner elbow microbiota. Furthermore, this survey indicated that a common core skin microbiome exists between these individuals. Segre adds that this finding is critical for studying disease. “Our long-term goal is to clarify the microbial contribution to a myriad of skin disorders both with known and suspected bacterial infections.” Segre’s group also found that the microbiota of mouse skin is comparable to that of the human inner elbow, suggesting a potential model for human skin disorders related to microbiota.

Segre explains that this work has established a foundation for answering questions about microbiota and skin disease, with the potential for novel drugs and treatments. “It’s not surprising that microbes play a vital role in human health and disease,” says Segre. “Unfortunately the public is conditioned to view microbes antagonistically, when in fact they may hold the key to a whole new array of therapeutic options.”

—————————-
Article adapted by Medical News Today from original press release.
—————————-

Scientists from the National Human Genome Research Institute (Bethesda, MD) and the National Cancer Institute (Bethesda, MD) contributed to this study.

This work was supported by the National Institute of General Medical Sciences, the National Human Genome Research Institute, and the National Cancer Institute.

About the article:

The manuscript is published online ahead of print on May 23, 2008. Its full citation is as follows: Grice, E.A., Kong, H.H., Renaud, G., Young, A.C., NISC Comparative Sequencing Program, Bouffard, G.G., Blakesley, R.W., Wolfsberg, T.G., Turner, M.L., and Segre, J.A. A diversity profile of the human skin microbiota. Genome Res. doi:10.1101/gr.075549.107.

About Genome Research:

Genome Research is an international, continuously published, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit http://www.cshlpress.com/.

Source: Peggy Calicchia
Cold Spring Harbor Laboratory

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D. audaxviator. Scanning electron micrograph. (Chivian et al, 2008)

2.8 km deep in a South African gold mine, Candidatus Desulforudis audaxviator lives a lonely existence. Growing at the rate of one cell division every 100 to 1000 years, it depends upon the radioactive decay of uranium as the energy source for its unique ecosystem. Audaxviator, Latin for “bold traveler,” contains all the metabolic machinery necessary for independent survival. The presence of genes for heterotrophy and genes derived from archaea suggests that this bug was not always on its own. It is likely that a bottleneck event ocurred, and audaxviator got lucky. Dr. Dylan Chivian of the Lawrence Berkeley National Laboratory and his colleagues used metagenomics techniques to determine the capabilities of the organism based on its genome. The microbe has not been isolated. It’s always exciting from an astrobiological standpoint to find unique ecosystems in environments considered to be particularly harsh!

image and info:

Dylan Chivian, et al. Environmental Genomics Reveals a Single-Species Ecosystem Deep Within Earth. Science 322, 275 (2008). http://www.sciencemag.org/cgi/content/abstract/322/5899/275.

Image via Wikipedia

I’ve recently attended a talk on the advancements of human metagenomics projects. As the speaker admitted, the whole field is a researchers’ gold mine – almost all they find is new and interesting. There were couple of interesting points – mainly concerning how limited our knowledge about things in here is. For example, there was a unconfirmed feeling among microbiologists that in fact all modern microbiology is nothing more than biology of E. coli and relatives. Now we know that for sure – number of known to us microbial species is estimated at 0.5% of all existing microbial species. Also, I heard a nice story about polish doctor who described in 19th century Helicobacter pylori and its role in gastric diseases (there was a Nobel prize for that in 2005), wrote a book and then trashed the whole thing because he couldn’t grow the bacteria in a pure culture. Another important issue was amount of data and lack of new ways of handling them.

But the most interesting for me was a connection between human microbiome and diseases. Or rather a possibility of such connection. I am not aware of any single case when composition of human microbiome have been proven to influence chance of getting ill and I don’t think there will be a lots of such correlations found soon. My impression is that correlations are to be found when we have both, a complete human genome and a complete metagenome of all that lives on particular person – a human genobiome, as I’ve called it (BTW, word “genobiome” is not present in Google – is there a better word for that?). And I believe that getting the first full human genobiome will be the achievement compared to sequencing human genome for the first time. Not because of technical difficulties – because of the all discoveries that need to be made to make it happen. For example, human gut of all people carries a species doing some sulfur reaction – but  its population is only up to few thousands cells. How many such cases are we have in our organisms? That is very good question. The field is brand new, and possibilities of speculations are endless.

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The human body is home to a diverse range of microorganisms, estimated to outnumber human cells in a healthy adult by ten fold. The importance of characterizing human microbiota for understanding health and disease is highlighted by the recent launch of the Human Microbiome Project by the National Institutes of Health. This report, published online in Genome Research (http://www.genome.org/), describes the investigation of healthy human skin for microbiota diversity and establishes the basis for determining a core microbiome.

The Human Microbiome Project aims to characterize the microbial communities of several regions of the body, including skin, where determining the core microbiome is essential to understanding and developing new treatments for skin conditions and diseases such as acne and atopic dermatitis (eczema). In this study, researchers led by Dr. Julie Segre of the National Human Genome Research Institute have generated a diversity profile of human skin microbiota by sequencing 16S rRNA, a component of the prokaryotic ribosome, isolated from a specific region of skin. “We focused this study on the inner elbow to inform future clinical studies of the extremely common inflammatory skin disorder atopic dermatitis, which affects this area of the skin and is associated with Staphylococcus infections,” explains Segre.

The researchers find that in the healthy subjects tested, Proteobacteria (predominantly Pseudomonas and Janthinobacterium) constituted the majority of inner elbow microbiota. Furthermore, this survey indicated that a common core skin microbiome exists between these individuals. Segre adds that this finding is critical for studying disease. “Our long-term goal is to clarify the microbial contribution to a myriad of skin disorders both with known and suspected bacterial infections.” Segre’s group also found that the microbiota of mouse skin is comparable to that of the human inner elbow, suggesting a potential model for human skin disorders related to microbiota.

Segre explains that this work has established a foundation for answering questions about microbiota and skin disease, with the potential for novel drugs and treatments. “It’s not surprising that microbes play a vital role in human health and disease,” says Segre. “Unfortunately the public is conditioned to view microbes antagonistically, when in fact they may hold the key to a whole new array of therapeutic options.”

—————————-
Article adapted by Medical News Today from original press release.
—————————-

Scientists from the National Human Genome Research Institute (Bethesda, MD) and the National Cancer Institute (Bethesda, MD) contributed to this study.

This work was supported by the National Institute of General Medical Sciences, the National Human Genome Research Institute, and the National Cancer Institute.

About the article:

The manuscript is published online ahead of print on May 23, 2008. Its full citation is as follows: Grice, E.A., Kong, H.H., Renaud, G., Young, A.C., NISC Comparative Sequencing Program, Bouffard, G.G., Blakesley, R.W., Wolfsberg, T.G., Turner, M.L., and Segre, J.A. A diversity profile of the human skin microbiota. Genome Res. doi:10.1101/gr.075549.107.

About Genome Research:

Genome Research is an international, continuously published, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit http://www.cshlpress.com/.

Source: Peggy Calicchia
Cold Spring Harbor Laboratory

Please rate this article:
(Hover over the stars
then click to rate) Patient / Public:
orHealth Professional:
Useful Links

I thank my colleague Suhail Rafudeen for alerting me to this:

 ”Some Of Our Oxygen Is Produced By Viruses Infecting Micro-organisms In The Oceans

ScienceDaily (Apr. 6, 2008) – Some of the oxygen we breathe today is being produced because of viruses infecting micro-organisms in the world’s oceans, scientists heard April 2, 2008 at the Society for General Microbiology’s 162nd meeting.

About half the world’s oxygen is being produced by tiny photosynthesising creatures called phytoplankton in the major oceans. These organisms are also responsible for removing carbon dioxide from our atmosphere and locking it away in their bodies, which sink to the bottom of the ocean when they die, removing it forever and limiting global warming.

“In major parts of the oceans, the micro-organisms responsible for providing oxygen and locking away carbon dioxide are actually single celled bacteria called cyanobacteria,” says Professor Nicholas Mann of the University of Warwick. “These organisms, which are so important for making our planet inhabitable, are attacked and infected by a range of different types of viruses.”

The researchers have identified the genetic codes of these viruses using molecular techniques and discovered that some of them are responsible for providing the genetic material that codes for key components of photosynthesis machinery.

“It is beginning to become to clear to us that at least a proportion of the oxygen we breathe is a by-product of the bacteria suffering from a virus infection,” says Professor Mann. “Instead of being viewed solely as evolutionary bad guys, causing diseases, viruses appear to be of central importance in the planetary process. In fact they may be essential to our survival.”

Viruses may also help to spread useful genes for photosynthesis from one strain of bacteria to another.

Adapted from materials provided by Society for General Microbiology, via EurekAlert!, a service of AAAS”

Fascinating concept: viruses as an essential link in the circle of life?!  Not so far-fetched, though: just because we know them largely because of their propensity to cause, and our fascination with, diseases that affect us and our livestock and crops…doesn’t mean that is all there is.

Viruses have been around as long as any other form of life, and it would be strange indeed if some form(s) of commensalism and/or symbiosis had not evolved.

…and see here for some fascinating speculations on the possible involvement of viruses with the origin of eukaryotes.

Dawn Field, Susanna-Assunta Sansone and George Garrity have been asked by the OMICS Editor and Chief Eugene Kolker to produce a special issue of OMICS based on the 5th GSC Workshop.

A community consultation has now started with the posting of the first paper on the GSC wiki. special issue of OMICS Wiki page Authors are strongly encouraged to circulate their papers widely, including to members of the GSC.

Please provide feedback directly to the authors or Editors (Dawn Field, George Garrity, Susanna-Assunta Sansone).

Further information:

Genomic Standards Consortium: http://gensc.org

Earlier post: special issue of OMICS

special issue of OMICS Wiki page

A poster will be presented at the Asia Pacific Bioinformatics Conference 2008 describing GenCat and the Genome Catalogue, two products of the Genomic Standards Consortium (GSC). If you are attending APBC 2008 and are interested in the work of the GSC, please contact Tanya Gray at tgra at ceh.ac.uk.

About the GSC:

The Genomic Standards Consortium (GSC) formed in 2005 with the aim to promote methods to standardize the description of genomes and the exchange and integration of genomics data.

The GSC is an open-membership international working body. Participants in the GSC include biologists, computer scientists, those building genomic databases and conducting large-scale comparative genomic analyses, and those with experience of building community-based standards.

For more information, please visit http://gensc.org

Products

The GSC has released a number of products:

MIGS/MIMS
Minimum Information about a Genome Sequence/Metagenome Sequence specification. Provides an extensions to the minimum information already captured by primary nucleotide databases (DDBJ/EMBL/Genbank) (Field et al, 2007).

GCDML
Genomic Contextual Data Markup Language that incorporates the MIGS/MIMS specification and provides an extended data capture and exchange mechanism for integrating a wide range of information relevant to the in depth description of genomes and metagenomes.

Genome Catalogue
A repository of genome reports that are compliant with the MIGS/MIMS specification. The Genome Catalogue is based on the GenCat software.

GenCat
A generic XML data catalogue tool that supports the development of data standards by providing a data repository and input forms auto-generated from successive XML schema files (used to define a data standard). (http://gencat.sf.net)

APBC 2008

http://sunflower.kuicr.kyoto-u.ac.jp/apbc2008/

At the recent Genomic Standards Consortium (GSC) workshop, George Garrity led discussions to review and produce a final version of the MIGS/MIMS checklist that will be included in the MIGS paper to be published in Nature Biotechnology in February 2008.

The revised version of the MIGS/MIMS checklist, together with comments recorded during the GSC workshop, are available via the GSC wiki at:

http://gensc.org/gc_wiki/index.php/MIGS_Checklist_Proofs

The MIGS/MIMS checklist document is available directly at:

http://gensc.sourceforge.net/docs/migsmims/

Nature Biotechnology Journal home page:

http://www.nature.com/nbt/index.html

Nature Biotechnology invited the scientific community to comment on the MIGS paper prior to publication. The community consultation page http://www.nature.com/nbt/consult/index.ht includes a link to the version of the MIGS paper made available for the community consultation:

Towards richer descriptions of our collection of genomes and metagenomes: the “Minimum Information about a Genome Sequence” (MIGS) specification (PDF 45K)

Dawn Field and Susanna-Assunta Sansone guest edited a special issue of the journal OMICS on data standards as an output of the 2nd GSC workshop. There were 22 invited papers including 5 in the area of standardization of genomic data (See: Special_Issue_of_OMICS).
An overview of the issue and its goals is captured in the foreword: http://www.liebertonline.com/doi/pdfplus/10.1089/omi.2006.10.84
The entire issue was open source and many of the papers in the issue continue to be at the top of the most downloaded list: http://www.liebertonline.com/action/showMostReadArticles?journalCode=omi

Special issue of OMICS from the 5th GSC Workshop

Dawn Field and George Garrity have been asked by the OMICS Editor and Chief Eugene Kolker to produce a special issue of OMICS based on the 5th GSC Workshop. After guaging interest in this prior to the workshop, and in response to developments at the workshop, we are going to accept this invitation.We are now considering proposals from the participants of the 5th GSC workshop (and their colleagues) for contributions on several key topics of special interest to the GSC.

Further information:

GSC web site: http://gensc.org

Dawn Field : contact info

George Garrity : contact info

Susanna-Assunta Sansone : contact info

Eugene Kolker : contact info

Further to the 5th Genomic Standards Consortium (GSC) workshop, slides are available to download from the GSC wiki:

agenda and presentations

On November 8th, Nature published two cool articles about metagenomic studies of twelve Drosophila (“fruit flies”) species. In the the first paper (click here), The Drosophila 12 Genomes Consortium (D12GG) compared the complete genomic sequences of the twelve Drosophila species, which included the model organism species Drosophila Melanogaster. Although the twelve species are related, they exhibit a surprising amount genetic biodiversity. For example, the evolutionary distance between D. Grimshawi and D. Melanogaster is the same distance as between humans and lizards. As a side note, six months earlier (in May 2007), PLoS Genetics published a similar metagenomic comparison of Drosophila (click here for the paper). In the PLoS paper, Hahn et al. present the (somewhat obvious) conclusion: “the apparent stasis in total gene number among species has masked rapid turnover in individual gene gain and loss.”

On November 8, Nature also published this paper (click here), in which Stark et al. (including Hahn) used the data from D12GG’s research to demonstrate a truly novel insight about the connection between conserved metagenomic sequence motifs and functional elements. The result of this paper allows us to infer the presence of functional elements with a accuracy far surpassing previous methods. Specifically, Stark et al. show how to infer the following functional elements, based on a metagenomic sample:

• Protein-coding regions: have highly constrained condon substitution regions, and indels have a bias for multiples of three.
• RNA genes: tolerate substitutions that preserve base pairing.
• miRNA: can be detected by looking for conserved palindromic stem sequences, which mutable loop sub-sequences between the two palindrome pieces.
• Regulatory motifs: have high levels of genome-wide conservation.
• Post-transcriptional motifs: are typically strand-based conservations.

Nobody who follows the scientific literature can possibly have missed the reports on Craig Venter’s metagenomics effort, trawling the oceans on his “Sorcerer II” yacht on the search for new DNA sequences. Unlike some of my fellow bloggers who know their metagenome, I have never been quite convinced that metagenomics is good for anything (except maybe for yachting on grant money).

This notion has changed today, when at around 2 pm CET, people in my group made an earth-shattering discovery while analysing some portion of the global ocean sampling data. It appears that the book on primate biology has to be re-written, or in other words, by overturning a century-old dogma, primate science is experiencing a veritable paradigm shift. To put our epochal discovery into context: Until recently, the smallest known primates were probably the pygmy mouse lemur (microcebus myoxinus), maybe this guy here. With a weight of 30-70 grams, and a length of 10-14 centimeters, these primates are firmly anchored within the macroscopic realm. However, as we have learned now, there is at least one more species of primates, living in the oceans, which has eluded us due to its small size.

By using most advanced computing hardware (HP dc7700) and software technology (BLAST), we were able to show that at least 1090 different sequences from various oceanic regions contain Alu elements, which are a hallmark of the primate genome. Our first suspicion was that the trawling device inadvertently sampled a Scuba diver, who did not manage to escape the subsequent homogenization step. However, this theory had to be abandoned, as i) the ocean sample sequences did not yield a perfect match to the human genome, ii) there was no homogenization step, and iii) the sampling procedure described in the original publication was selective for the size range of 0.1–0.8-μm, which does not accommodate divers.

Thus, we are currently pursuing alternative explanations, the most likely of which is the existence of a hitherto unnoticed ocean dwelling micro-primate. While our analyses are still ongoing, the results obtained so far fully support this theory. Not only are the ocean-derived Alu elements and their flanking DNA sequences distinct from the human genome, they also do not match the genome of J.C. Venter, J.D. Watson, or any other sequenced model primate. We are currently trying to obtain more genomic information on this elusive primate, which might give us hints to its evolutionary ancestry and its planktonic habitat. A first important observation in that respect is the apparent overabundance of DNA fragments derived from odorant receptors. This enrichment suggests that the micro-primate makes thorough use of its olfactory sense, most likely for finding nutrients and evading predators.

There is little doubt that the bioinformatical discovery of the micro-primate will have as far-reaching consequences as the ant populations living in outer space, which were identified in 1999 through the discovery of dense clumps of formic acid in interstellar molecular clouds.

Update:

I have adjusted some numbers and links in the main article. For those interested in further pursuing this line of research, here is a list of the Alu-containing ocean samples. Unfortunately, we don’t have enough time to work on this, as we are already preparing our next scoop: a comprehensive metagenomic analysis of the ALH84001 meteorite.

In case anyone is interested, Science will be hosting an online discussion on the metagenomics of Honey Bee colony collapse disorder next week (Oct 24 2007, 12 – 5pm EST). Speakers include Dr. W Ian Lipkin (Columbia University) and Dr. Michael Egholm (454 Life Sciences).

From the description on the seminar homepage:

Colony collapse disorder (CCD) among honey bee populations in the United States has resulted in the loss of between 50% and 90% of hive colonies. Previous studies have pointed to the possibility that an infectious agent could be involved. A recent study published in Science magazine used unbiased metagenomic analysis to survey microflora present in normal and CCD-affected hives to determine whether a pathological agent could be linked to CCD. The authors found that the presence of one virus, Israeli acute paralysis virus of bees (IAPV), showed a strong correlation with colony collapse disorder. In addition to the important economical implications, this work also represents a novel use for massively parallel next generation sequencing technology which has enabled this type of high level metagenomic study.

You will hear our panel, which includes two of the study’s authors, discussing:

• How metagenomics can be applied in the discovery of unknown pathogens.
• The importance of study design and data analysis in metagenomics research.
• How recent technological advances have made this type of study possible ovarian cancer

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Registration is required, but is open to anyone interested.

A peine j’ai eu le temps de revenir vers ma biblio quotidienne, après la lecture du papier de Wired que mentionne DNAcowboy à son commentaire au sujet des tests ADN, que je tombe sur ce papier “Multilocus OCA2 genotypes specify human iris colors.”, par Frudakis T, Terravainen T, Thomas M., ou Tony Frudakis est le même qui avait été interviewé par Wired.

Je n’ai pas accès à Human Genetis, je reste donc sur ma faim avec l’abstract:
Addendum : il suffit de jeter un coup d’oeil à Scienblogs pour trouver un peu plus quand la frustration vous guète Razib, à Gene Expression en parle et visiblement il a lu le papier.

Human iris color is a quantitative, multifactorial phenotype that exhibits quasi-Mendelian inheritance. Recent studies have shown that OCA2 polymorphism underlies most of the natural variability in human iris pigmentation but to date, only a few associated polymorphisms in this gene have been described. Herein, we describe an iris color score (C) for quantifying iris melanin content in-silico and undertake a more detailed survey of the OCA2 locus (n = 271 SNPs). In 1,317 subjects, we confirmed six previously described associations and identified another 27 strongly associated with C that were not explained by continental population stratification (OR 1.5-17.9, P = 0.03 to <0.001). Haplotype analysis with respect to these 33 SNPs revealed six haplotype blocks and 11 hap-tags within these blocks. To identify genetic features for best-predicting iris color, we selected sets of SNPs by parsing P values among possible combinations and identified four discontinuous and non-overlapping sets across the LD blocks (p-Selected SNP sets). In a second, partially overlapping sample of 1,072, samples with matching diplotypes comprised of these p-Selected OCA2 SNPs exhibited a rate of C concordance of 96.3% (n = 82), which was significantly greater than that obtained from randomly selected samples (62.6%, n = 246, P<0.0001). In contrast, the rate of C concordance using diplotypes comprised of the 11 identified hap-tags was only 83.7%, and that obtained using diplotypes comprised of all 33 SNPs organized as contiguous sets along the locus (defined by the LD block structure) was only 93.3%. These results confirm that OCA2 is the major human iris color gene and suggest that using an empirical database-driven system, genotypes from a modest number of SNPs within this gene can be used to accurately predict iris melanin content from DNA.

Il y a des moments où je me dis que je n’ai pas pris la Science du côté où ça paie. Merde ! Ils en sont à EuropeanDNA 2.0 Product ! 2.0, ouah !

I am little confused after reading about the metagenomics approach that identified the causative agent for the colony collapse disorder which Deepak and myself blogged about.

After trolling through pubmed , it seems like a number of the honeybee potential pathogens were already quite well known. The Kashmir bee virus and the Israeli acute Paralysis virus were also lurking among bee populations. Was is not then possible to query this with a quick microarray designed following some text and sequence mining .

Or maybe its just faster to just sequence the whole bee and then perform the in vitro RT-PCR experiments which are a little more targeted.

Maybe this does say something about the difficulty of on the fly bioinformatics driven microarray fabrication . Since the closest I have come to a microarray experiment is seeing the images on the web .. I was just wondering aloud..I am hardly an expert

Addendum: There is of course no denying the added benefits of the metagenomic approach . Like the many other conclusions the paper made possible- that mite levels in both CCD and non-CCD samples were similar , that microflora ( like the bacteria in the bee gut) among Australian and American bees are similar . So I guess the question then is ..maybe metagenomics is just so much more direct that its going to be the first choice in all such open ended questions like ” What causes infectious Disease X”