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Major Breakthrough: FANTOM5 Releases Comprehensive Atlas of Human Gene Expression

Discussion in 'Other Health News and Research' started by Ecoclimber, Mar 27, 2014.

  1. Ecoclimber

    Ecoclimber Senior Member

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    A large international consortium of researchers has produced the first comprehensive, detailed map of the way genes work across the major cells and tissues of the human body. The findings describe the complex networks that govern gene activity, and the new information could play a crucial role in identifying the genes involved with disease.

    The work is published in 16 major journals including Nature, PNAS, PLos One, Science, etc. listed here:


    FANTOM5 Releases Comprehensive Atlas of Human Gene Expression


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    Whereas the human genome project mapped every gene in the human genome, the FANTOM project has been mapping which genes are active. And now, with the culmination of the project’s fifth stage, FANTOM has released the most detailed picture yet of how human genetic material is regulated. The work amounts to a grand circuit diagram of the network of switches, built into human DNA, that controls when and where genes are turned on and off.

    Two landmark papers appeared March 26 in Nature, accompanied by 16 studies published in Nature Biotechnology, Genome Research, Blood, Molecular Biology and Evolution, Proceedings of the National Academy of Sciences, Nucleic Acids Research, Molecular Genetics and Metabolism, BMC Genomics, and PLoS ONE.

    The papers published in Nature describe maps of promoters and enhancers—short regions of DNA that influence the activity of genes—encoded in the human genome, and their activity across the vast wealth of human cell types and tissues of the human body. Together with the other studies published by FANTOM5, this data provides the first complete view of the networks regulating transcription across all cell types.

    The FANTOM project (for functional annotation of the mammalian genome) is a RIKEN initiative launched in 2000 to build a complete library of human genes using the capabilities offered by new, state-of-the-art cDNA technologies. Over 250 experts in primary cell biology and bioinformatics from 114 institutions based in more than 20 countries and regions worked as part of FANTOM5.

    The researchers involved in the two Nature papers used a highly sensitive technique called cap analysis of gene expression (CAGE), developed at RIKEN, to monitor the activity of promoters and enhancers.
    The first Nature paper (“An atlas of active enhancers across human cell types and tissues”) presents an atlas of active, in vivo bidirectionally transcribed enhancers across the human body: “Based upon the FANTOM5 CAGE expression atlas encompassing 432 primary cell, 135 tissue, and 241 cell line samples from human, we identify 43,011 enhancer candidates and characterize their activity across the majority of human cell types and tissues.” The researchers indicated that the activity of the large majority of these transcriptional regulation regions is highly specific to cell type.

    The authors report using the atlas to “compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers.” In addition, the authors explored the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The authors concluded that the FANTOM5 enhancer atlas, which is available online, represents a unique resource for studies on cell-type-specific enhancers and gene regulation.

    The second Nature paper (“A promoter level mammalian expression atlas”) used single-molecule sequencing to map human and mouse transcription start sites and their usage in a panel of distinct human and mouse primary cells, cell lines, and tissues to produce the most comprehensive mammalian gene expression atlas to date.
    According to a Nature editor’s summary, the data provide “a plethora of insights into open reading frames and promotes across different cell types in addition to valuable annotation of mammalian cell-type-specific transcriptomes."

    The significance of having compiled an atlas of human gene expression was explained by Dr. Alistair Forrest, scientific coordinator of FANTOM5: “Humans are complex multicellular organisms composed of at least 400 distinct cell types. This beautiful diversity of cell types allow us to see, think, hear, move, and fight infection, yet all of this is encoded in the same genome. The difference between all these cells is what parts of the genome they use—for instance, brain cells use different genes than liver cells, and therefore they work very differently.

    In FANTOM5, we have for the first time systematically investigated exactly what genes are used in virtually all cell types across the human body, and the regions which determine where the genes are read from the genome.”

    Looking forward to applications inspired by FANTOM5's work, Dr. Yoshihide Hayashizaki, the general director of FANTOM, offerered these remarks: “The basic library of cell definition that was produced during FANTOM5 is a remarkable step to manipulating cells. The library will be an essential resource for developing a wide range of technologies for the life sciences, that will lead to the development of regenerative and personalized medicine in the near future.”


    First comprehensive atlas of human gene activity released

    For immediate release: Wednesday, March 26, 2014

    Boston, MA — A large international consortium of researchers has produced the first comprehensive, detailed map of the way genes work across the major cells and tissues of the human body. The findings describe the complex networks that govern gene activity, and the new information could play a crucial role in identifying the genes involved with disease.

    “Now, for the first time, we are able to pinpoint the regions of the genome that can be active in a disease and in normal activity, whether it’s in a brain cell, the skin, in blood stem cells or in hair follicles,” said Winston Hide, associate professor of bioinformatics and computational biology at Harvard School of Public Health (HSPH) and one of the core authors of the main paper in Nature. “This is a major advance that will greatly increase our ability to understand the causes of disease across the body.”

    The research is outlined in a series of papers published March 27, 2014, two in the journal Nature and 16 in other scholarly journals. The work is the result of years of concerted effort among 250 experts from more than 20 countries as part of FANTOM 5 (Functional Annotation of the Mammalian Genome).

    The FANTOM project, led by the Japanese institution RIKEN, is aimed at building a complete library of human genes.

    Researchers studied human and mouse cells using a new technology called Cap Analysis of Gene Expression (CAGE), developed at RIKEN, to discover how 95% of all human genes are switched on and off. These “switches”—called “promoters” and “enhancers”—are the regions of DNA that manage gene activity. The researchers mapped the activity of 180,000 promoters and 44,000 enhancers across a wide range of human cell types and tissues and, in most cases, found they were linked with specific cell types.

    “We now have the ability to narrow down the genes involved in particular diseases based on the tissue cell or organ in which they work,” said Hide. “This new atlas points us to the exact locations to look for the key genetic variants that might map to a disease.”

    Funding for FANTOM 5 came from a research grant from RIKEN and from Innovative Cell Biology.
    “A promoter-level mammalian expression analysis,” Alistair R. R. Forrest; Hideya Kawaji; J. Kenneth Baillie; Michiel J. L. de Hoon; Timo Lassmann; Masayoshi Itoh; Kim M. Summers, Harukazu Suzuki, Carsten O. Daub, Jun Kawai, Peter Heutink, Winston Hide, Tom C. Freeman, Boris Lenhard, Vladimir B. Bajic, Martin S. Taylor, Vsevolod J. Makeev, Albin Sandelin, David A. Hume, Piero Carninci and Yoshihide Hayashizaki, Nature, March 27, 2014, doi:10.1038/nature13182, 2014

    For more information:
    Todd Datz
    617.432.8413
    tdatz@hsph.harvard.edu
    Last edited: Mar 27, 2014
    Waverunner, Valentijn and rosie26 like this.

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