Fastest ever profile of bugs in the gut (A new tool has profiled the metagenome of the microbe community inhabiting the human gut with unparalleled speed and accuracy)



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News · Health & Mind · Life & Environment · Technology
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Fastest ever profile of bugs in the gut
Monday, 11 June 2012
by Jude Dineley

Cosmos Online

The leap in speed and accuracy of profiling the metagenome of the
microbe community will build a comprehensive picture of suspect
communities associated with a range of medical conditions including
Crohn’s disease and diabetes.
Credit: iStockphoto

SYDNEY: A new tool has profiled the metagenome of the microbe
community inhabiting the human gut with unparalleled speed and
accuracy, which will advance research into the diagnosis and treatment
of metabolic and digestive diseases.

With advancement in the MetaPhiAn tool, researchers are now able to
profile the composition of microbe communities in hours, compared to
the months it would take a supercomputer using conventional
techniques.

The leap in speed and accuracy will build a comprehensive picture of
suspect communities associated with a range of medical conditions
including Crohn’s disease and diabetes.

Identifying microbes & how they behave

“The two big questions for microbial communities are typically, ‘Who's
there?’ and, ‘What are they doing?’ That is, which microbes are
present, and what biological activities are they carrying out in
response to or as an influence on their environment,” said Curtis
Huttenhower, senior author of the paper published in Nature Methods
and specialist in computational biology at Harvard University, in
Boston.

“MetaPhlAn answers the first [question] very precisely, and it does so
fast enough to keep up with the tremendous amount of microbiome
sequencing data we can now produce - a typical sequencing center now
produces about a million times more DNA sequence than it did ten years
ago during the Human Genome Project!” said Huttenhower.

Metagenome analysis: a mammoth task

The human microbiome is a diverse community of beneficial and,
occasionally, harmful microbes that inhabit the body. It consists
mainly of bacteria and outnumbers our own cells by a factor of ten.
According to first author, computer scientist Nicola Segata, it’s
community profiles in the gut rather than specific microbes that are
associated with conditions such as Crohn’s disease.

“We thus need to investigate all microbes – whether beneficial,
pathogenic, or unknown - present in a microbiome and their
proportions, in other words a microbiome quantitative taxonomic
profile,” said Segata.

But the task is a mammoth one, with up to 750 billion DNA sequences
per dataset requiring analysis. Conventional techniques are either too
slow or of limited accuracy, motivating the researchers to develop a
more efficient way of generating a taxonomic profile of the biome.

The researchers improved profiling accuracy by first identifying
unique “name tags” – short DNA sequences particular to each microbial
species. These tags were used to build a reference library of microbe
signatures. The library provides a quick and easy way for the computer
to check for each microbe and its abundance when a real, live microbe
community is analysed.

Segata likens the approach to counting the number of elephant trunks
as a proxy for the number of elephants, “in the biome genome we need
to find something discriminative in each microbe species, like trunks
for elephants.”

Uncovering the link between microbe communities & disease

“Given MetaPhlAn's high sensitivity and specificity, I hope that it
will contribute to our ability to associate specific microbes with
genetic variants in human hosts, which is a big open question in the
study of the microbiome right now,” said Huttenhower.

“It also allows us to survey microbial genetic variation - whether
there are changes not just in human genes, but in microbial genes in
the microbiome, that influence human health,”

The Harvard researchers have already started to use the tool in
several clinical studies, including biome comparisons of healthy
individuals and those with inflammatory bowel disease and surveys
identifying locations in the human body where a harmful balance of
microbes might occur.

Commenting on the research, Lutz Krause, a bioinformatician at the
Queensland Institute of Medical Research in Brisbane said “the main
bottleneck in metagenomics is not the research budget or sequencing
facilities, but the computational analysis of the complex and
multidimensional data sets produced.”

“These challenges are tackled by the proposed method using an
innovative novel computational approach, and now large metagenomic
datasets can be rapidly analysed on a desktop computer. This program
is a further step towards the automated analysis of large metagenomic
samples,” said Krause.



More information

Homepage for the MetaPhlAn Project, Huttenhower Lab, Harvard

The Human Microbiome Project



http://www.cosmosmagazine.com/news/5669/fastest-ever-profile-bugs-gut
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