Too many sequences, and now what?                              by Omar Delannoy

2/28/2013

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Picture*Image from redOrbit.com
All hail to the computer scientists and their bioinformatics tools!

Let's say you are now ready to analyze your sequencing data. However, you have no idea what bioinformatics tools are available and which ones are the most convenient to use for your specific experiments. Well, if you didn't realize this before, it would be better for you to know that metagenomics is a field that is more suitable for the people that are savvy in computer languages or with experience in bioinformatics tools. But, don't let this get you down. There is still time to acquire skills in computer sciences, and you can even have fun during the process (for more information regarding computational tools that are useful for solving biological problems, visit this link).

Now, in relation to the metagenomic sequences, there are many options available that you can use for analyzing your data. The approach that you decide to use will depend greatly on your research objectives, and in the questions you want to answer. With this in mind, it is important that you understand some of the experimental and computational steps you have to cover during the acquisition and analysis of your data.

Below is a diagram that illustrates the experimental and computational steps that are necessary for a metagenomics study:
Picture
*Diagrams were modified from Thomas, et al. (2012), and from Angly, et al. (2009).
Houston, we have a solution!

In the brink of desperation, when nothing works and you have no clue whatsoever of what bioinformatics tools are available and which ones are the right ones to use for your experiment, there is still a chance for not letting anxiety take the best of you. Many bioinformaticians around the world are working in the development of better tools for analyzing genomic data. You can access some of these computational tools  by clicking the items on the list below:
  • Metagenomic sequence pre-filtering
          – Eu-Detect
          – DeconSeq
  • Metagenomic-specific assembly
          – Meta-IDBA (de Novo assembler for metagenomic data)
          – MetaVelvet (de Novo assembler for metagenomic data)
          – Celera Assembler
          – Newbler
          – Genovo
          – Phrap          
          – MAP (Metagenomic Assembly Program)
          – MetAMOS
  • Assembly quality evaluation
          – Gage
          – QUAST
  • Metagenome analyzers (Gene prediction)
         – MEGAN 4
         – GeneMark
         – GLIMMER
  • Metagenomic and/or profile species diversity analysis
         – QIIME
         – PhymmBL
         – MetaPhlAn

These and other tools are still available online and most are open-source. If you are interested in this topic and want more information about these computational approaches for analyzing your metagenomic data, I'll recommend that you take a look at the Metagenomics Informatics Challenges Workshop 2011 organized by the US Department of Energy Joint Genome Institute (JGI). In this series of talks, scientists discussed the capabilities and advantages of some of the computational tools that I mentioned in the list before. All the talks from the workshop are now available on YouTube. In the video below, you can watch the introductory talk to these workshops.

Good luck on your analysis!

*References:
(1) Angly et al. (2009) The GAAS metagenomic tool and its estimations of viral and microbial average genome size in four major biomes. PLoS Comput Biol. 5(12): e1000593.
(2) Hamady, M., and Knight, R. (2009) Microbial community profiling for human microbiome projects: Tools, techniques, and challenges. Genome Res. 19: 1141–1152.
(3) Kalyuzhnaya, M.G. et al. (2008) High-resolution metagenomics targets specific functional types in complex microbial communities. Nature Biotechnology 26(9): 1029–1034.
(4) Kunin, V. et al. (2008) A bioinformatician’s guide to metagenomics. Microbiol. Mol. Biol. Rev. 72(4): 557–578.
(5) Simon, C., and Daniel, R. (2011) Metagenomic analyses: past and future trends. Appl. Environ. Microbiol. 77(4): 1153–1161.
(6) Thomas et al. (2012) Metagenomics- a guide from sampling to data analysis. Microbial Informatics and Experimentation 2:3.
(7) Wooley, J.C., and Ye, Y. (2009) Metagenomics: facts and artifacts, and computational challenges. J Comput Sci Technol. 25(1): 71–81.
(8) Xu, J. (2006) Microbial ecology in the age of genomics and metagenomics: concepts, tools, and recent advances. Molecular Ecology 15: 1713–1731.
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What's on the menu? Microbes! by Omar Delannoy

2/27/2013

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Picture* Image from Cho and Blaser (2012) Nature Reviews Genetics
A catalogue of microbes in the human gut

It comes to my attention how our knowledge of the microbial world is rapidly expanding throughout the years. As of today, researchers are able to identify most of the microorganisms that inhabit a specific environment in an ecosystem, including parts of our bodies (see image on the left). Now is known, that the set of microbes, their genomes and their environmental interactions that are associated within our bodies (here forth termed as the human microbiome) have an important role in human health. This is reason of why many scientists around the world are paying attention to microbes and their role in diseases and other medical-related conditions.

The human microbiome project was developed with the purpose of understanding all the microbial communities (including their genomes and their interactions) that are associated to humans. Their aim, as is presented on their website, reads as follow:
"The aim of the HMP is to characterize microbial communities found at multiple human body sites and to look for correlations between changes in the microbiome and human health."
Picture*Figure from Qin, et al. (2010) Nature
In addition to the human microbiome project, researchers from Europe and China collaborated to develop the MetaHit (Metagenomics of the Human Intestinal Tract) project. This project lasted from 2008 – 2012, and with it, many scientific discoveries were published (look video below for more information about the project). Among those discoveries, it is worthwhile to mention the work of Qin, et al. (2010) from the MetaHIT Consortium, about the human gut microbial gene catalogue.

In this article, using deep metagenomic sequencing, the authors managed to identify and characterize a catalogue of microbial genes (encoded in their metagenomes) that were present in the gut of individuals with obesity/diabetes phenotypes, patients with Crohn's disease or ulcerative colitis, and healthy individuals. They were able to study these metagenomes due to the power of the new emerging sequencing technologies. Their results showed that the microorganisms that predominated in the gut of the individuals that were studied belong to the phyla Firmicutes and Bacteroidetes. In addition, they noted a significant difference in the species abundance of the core microbiota of healthy individuals and patients with Crohn's disease or ulcerative colitis (figure shown above). These results might suggest a possible role of specific microbial species in the progression of inflammatory bowel disease in patients suffering from such diseases.

With the advancement of these sequencing technologies, we could easily predict how medicine will change in the near future. With years to come, and as long as technologies continue to grow, we might be able to diagnose and medicate patients individually according to their genomic and metagenomic background. In this way, treatments could be more specific and more accurate, leading to a better diagnosis and a faster recovery.

*References:
(1) Cho, I., and Blaser, M.J (2012) The human microbiome: at the interface of health and disease. Nature Reviews Genetics 13: 260–270.
(2) Qin, J., Li, R., Raes, j., et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(4): 59–67.
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The omics movement in the microbe world                  by Omar Delannoy

2/27/2013

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Picture*Image from clinical-bioinformatics.com
Next Generation Sequencing (NGS) technologies to the rescue!

It wasn’t long ago when sequencing genomes were a very expensive and tiresome procedure. Nowadays, with the emergence of Next Generation Sequencing (NGS) technologies (for more information regarding these technologies, visit the following link), we are able to test many biological problems that were nearly impossible to work with in past years.

These technologies had also contributed in the development of new areas of research that followed, in close range, the omics movement. Genomics and more recently metagenomics fields emerge from the application of these technologies. Since these new approaches became readily available, scientists all over the world took advantage of these NGS technologies and began doing novel research in different areas of biology that resulted in surprising discoveries. One of these scientists was Dr. J. Craig Venter, a famous North American biologist and entrepreneur. In addition to his outstanding contributions in the determination of all the sequences in the human genome (see human genome project), he pioneered in using NGS technologies as a mean for cataloguing the metagenomes of millions of microbial species in different marine environments (see video below). As a result, he was able to determine the tremendous microbial diversity that dominated such marine environments, and he could also identify a vast collection of microbial genes with possible roles in metabolic pathways and with importance to the ecosystem (for more information see Venter, et al. 2004).

As NGS technologies continues to grow, new approaches for studying microorganisms will become available. To me, it would not be surprising if in the near future we encounter that our microscopic friends happened to be involved in important processes in the development and evolution of organisms. These new discoveries could have a huge impact in our understanding of biological processes that could change our perception in how we study human diseases, such as cancer, inflammable bowel diseases, asthma, diabetes, etc. This is the reason of why we can not overlook the presence of microbes in any biological study.

*References:
(1) Venter, J.C., et al. (2004) Environmental genome shotgun sequencing of the Sargasso Sea. Science 304(5667): 66–74.
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Are you ready for a career in Metagenomics?               By Omar Delannoy

2/27/2013

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Bringing you closer to metagenomics!

I am very excited to know that you have selected (or are thinking in selecting) the field of metagenomics as a career path for your future. In this field, we strive to uncover and to reveal the secrets of our microbial planet. If you wish to explore more about this topic, I'll recommend that you read the book: "The New Science of Metagenomics", from the National Academy of Sciences (book cover image to the right). This book exquisitely explains the importance of this field.

Most of us graduate students often face with the unstable confusion of not knowing how to analyze metagenomics data. There are too many programs available on the internet, yet it is not cleared which ones are more fitted for our analysis. This is the time when we often succumb in an abyss of uncertainty, and our brains are more likely to explode.
Picture
*Image from National Academy of Sciences
Well my fellow Metagenomic adventurers, we all have been there at some point of our lives. Luckily, there is good news for us. There are many workshops, small technical courses, seminar series, and summer courses that are offered throughout the year at many institutions that can help you stay on the right track.

Here, I'll show you a list of some programs that are useful for training students, professors and professionals in analyzing metagenomic data.

1) Marine Biological Laboratories (MBL)
     – Summer Course in Microbial Diversity
        (usually lasts 6 weeks | Deadline: Early February of each year)
     – Special Topics in Strategies and Techniques for Analyzing Microbial Population
        Structures
         (usually lasts 11 days | Deadline: Early April of each year)
2) European Molecular Biology Laboratory (EMBL)
     – Practical course in Metagenomics: From the Bench to Data Analysis
        (usually lasts 1 week | It is scheduled during April)
3) EMBL–European Bioinformatics Institute (EBI)
     – Training course in Metagenomics: Managing, Analysing and Visualising Data
        (usually lasts 3 days | Deadline: July 12, 2013)
4) University of Oslo, Department of Biosciences
     – Course in Bioinformatics for metagenomic analyses and environmental
        sequencing
        (usually lasts 5 days | It is scheduled during March)
5) DOE Joint Genome Institute
     – Workshops in Microbial Genomics and Metagenomics
        (usually lasts 5 days | Scheduled throughout different dates, usually in February,
        May and September)

Well, there you have it. If you happen to know of other courses that are useful for microbiologists, please, let me know in the comment section.

Good luck on your analysis!
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Why study microbes? by Omar Delannoy

2/26/2013

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Picture*Image extracted from The National Academies
A microbial world indeed...

We live in a planet that is completely dominated by microorganisms. About half of Earth's total biomass is entirely composed of microbes, whereas animals just make up about 1/1000th of the biomass. So far, our knowledge of microbes is very limited and is very restricted to those microorganisms that play a role as pathogens to humans and other economically important organisms (e.g. farm animals, lab animals, agricultural plants, etc.).

With the emergence of Next Generation Sequencing (NGS) technologies, we can expand this knowledge and begin studying microorganisms at a larger scope.

Now is the time to embrace the microbiological sciences. Better yet, to make extraordinary discoveries about the function and role of microbes in every ecosystem. This is where NGS comes handy. High-throughput sequencing techniques are offering us the opportunity to study microbial communities at a large scale, in a field that is now known as metagenomics. 
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