• New technology enables unprecedented gli

    From ScienceDaily@1:317/3 to All on Wed Mar 9 21:30:48 2022
    New technology enables unprecedented glimpse inside single brain cells
    Platform will provide open-source cell catalogue to better understand
    brain diseases

    Date:
    March 9, 2022
    Source:
    Salk Institute
    Summary:
    Researchers have developed a new genomic technology to
    simultaneously analyze the DNA, RNA and chromatin -- a combination
    of DNA and protein - - from a single cell. The method, which took
    five years to develop, is an important step forward for large
    collaborations where multiple teams are working simultaneously to
    classify thousands of new cell types. The new technology will help
    streamline analyses.



    FULL STORY ==========================================================================
    Salk Institute researchers have developed a new genomic technology to simultaneously analyze the DNA, RNA and chromatin -- a combination of
    DNA and protein -- from a single cell. The method, which took five years
    to develop, is an important step forward for large collaborations where multiple teams are working simultaneously to classify thousands of new
    cell types. The new technology, published in Cell Genomics on March 9,
    2022, will help streamline analyses.


    ========================================================================== "This multimodal platform is going to be useful by providing a
    comprehensive database that can be used by the groups trying to integrate
    their single- modality data," says Joseph Ecker, director of the Genomic Analysis Laboratory at Salk, the Salk International Council Chair in
    Genetics and Howard Hughes Medical Institute Investigator. "This new information can also inform and guide future cell-type classification."
    Ecker believes this technology will be vital for large-scale efforts,
    such as the National Institutes of Health's BRAIN Initiative Cell Census Network, which he co-chairs. A major effort of the BRAIN Initiative is to develop catalogues of mouse and human brain cell types. This information
    can then be used to better understand how the brain grows and develops, as
    well as the role different cell types play in neurodegenerative diseases,
    such as Alzheimer's.

    Current single-cell technology works by extracting either DNA, RNA
    or chromatin from a cell's nucleus, and then analyzing its molecular
    structure for patterns.

    However, this method destroys the cell in the process, requiring
    researchers to rely on computational algorithms to analyze more than
    one of these components per cell or to compare the results.

    For the new method, called snmCAT-seq, scientists used biomarkers to tag
    DNA, RNA and chromatin without removing them from the cell. This allowed
    the researchers to measure all three types of molecular information in
    the same cell. The scientists then used this method to identify 63 cell
    types in the frontal cortex region of the human brain and benchmarked the efficacy of computational methods for integrating multiple single-cell technologies. The team found the computational methods have high
    accuracy in characterizing broadly defined brain-cell populations but
    show significant ambiguity in analyzing finely defined cell types,
    suggesting the necessity to define cell types by diverse measurements
    for more accurate classification.

    The technology could also be used to better understand how genes and
    cells interact to cause neurodegenerative diseases.

    "These diseases can broadly affect many cell types. But there could
    be certain cell populations that are particularly vulnerable," says
    co-first author Chongyuan Luo, assistant professor of human genetics
    at the David Geffen School of Medicine at UCLA. "Genetic research has pinpointed the regions of the genome that are relevant for diseases
    like Alzheimer's. We're providing another data dimension and identifying
    the cell types affected by these genomic regions." As a next step, the
    team plans to use the new platform to survey other areas of the brain,
    and to compare cells from healthy human brains with those from brains
    affected by Alzheimer's and other neurodegenerative diseases.

    Other authors included Hanqing Liu, Bang-An Wang, Zhuzhu Zhang, Dong-Sung
    Lee, Jingtian Zhou, Sheng-Yong Niu, Rosa Castanon, Anna Bartlett,
    Angeline Rivkin, Jacinta Lucero, Joseph R. Nery, Jesse R. Dixon and
    M. Margarita Behrens of Salk; Fangming Xie, Ethan J. Armand, Wayne
    I. Doyle, Sebastian Preissl and Eran A. Mukamel of the University of
    California San Diego; Kimberly Siletti, Lijuan Hu and Sten Linnarsson
    of the Karolinska Institutet in Sweden; Trygve E.

    Bakken, Rebecca D. Hodge and Ed Lein of the Allen Institute for Brain
    Science in Seattle; Rongxin Fang, Xinxin Wang, and Bing Ren of the Ludwig Institute for Cancer Research in La Jolla, California; Tim Stuart and
    Rahul Satija of the New York Genome Center; and David A. Davis and
    Deborah C. Mash of the University of Miami.

    The research was supported by the National Institutes of Health
    (5R21HG009274, 5R21MH112161, 5U19MH11483, R01MH125252, U01HG012079, 5T32MH020002, R01HG010634 and U01MH114812), the Howard Hughes Medical
    Institute and UC San Diego School of Medicine.


    ========================================================================== Story Source: Materials provided by Salk_Institute. Note: Content may
    be edited for style and length.


    ========================================================================== Journal Reference:
    1. Chongyuan Luo, Hanqing Liu, Fangming Xie, Ethan J. Armand, Kimberly
    Siletti, Trygve E. Bakken, Rongxin Fang, Wayne I. Doyle, Tim
    Stuart, Rebecca D. Hodge, Lijuan Hu, Bang-An Wang, Zhuzhu Zhang,
    Sebastian Preissl, Dong-Sung Lee, Jingtian Zhou, Sheng-Yong Niu,
    Rosa Castanon, Anna Bartlett, Angeline Rivkin, Xinxin Wang,
    Jacinta Lucero, Joseph R.

    Nery, David A. Davis, Deborah C. Mash, Rahul Satija, Jesse R. Dixon,
    Sten Linnarsson, Ed Lein, M. Margarita Behrens, Bing Ren, Eran
    A. Mukamel, Joseph R. Ecker. Single nucleus multi-omics identifies
    human cortical cell regulatory genome diversity. Cell Genomics,
    2022; 2 (3): 100107 DOI: 10.1016/j.xgen.2022.100107 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220309131828.htm

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