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  • Cold Spring Harbor Laboratory  (2)
  • Chen, Xi  (2)
  • Medicine  (2)
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  • Cold Spring Harbor Laboratory  (2)
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  • Medicine  (2)
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  • 1
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 29, No. 4 ( 2019-04), p. 682-696
    Abstract: The origination of new genes contributes to phenotypic evolution in humans. Two major challenges in the study of new genes are the inference of gene ages and annotation of their protein-coding potential. To tackle these challenges, we created GenTree, an integrated online database that compiles age inferences from three major methods together with functional genomic data for new genes. Genome-wide comparison of the age inference methods revealed that the synteny-based pipeline (SBP) is most suited for recently duplicated genes, whereas the protein-family–based methods are useful for ancient genes. For SBP-dated primate-specific protein-coding genes (PSGs), we performed manual evaluation based on published PSG lists and showed that SBP generated a conservative data set of PSGs by masking less reliable syntenic regions. After assessing the coding potential based on evolutionary constraint and peptide evidence from proteomic data, we curated a list of 254 PSGs with different levels of protein evidence. This list also includes 41 candidate misannotated pseudogenes that encode primate-specific short proteins. Coexpression analysis showed that PSGs are preferentially recruited into organs with rapidly evolving pathways such as spermatogenesis, immune response, mother–fetus interaction, and brain development. For brain development, primate-specific KRAB zinc-finger proteins (KZNFs) are specifically up-regulated in the mid-fetal stage, which may have contributed to the evolution of this critical stage. Altogether, hundreds of PSGs are either recruited to processes under strong selection pressure or to processes supporting an evolving novel organ.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2019
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2020
    In:  Genome Research Vol. 30, No. 4 ( 2020-04), p. 622-634
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 30, No. 4 ( 2020-04), p. 622-634
    Abstract: A time course experiment is a widely used design in the study of cellular processes such as differentiation or response to stimuli. In this paper, we propose time course reg ulatory analysis (TimeReg) as a method for the analysis of gene regulatory networks based on paired gene expression and chromatin accessibility data from a time course. TimeReg can be used to prioritize regulatory elements, to extract core regulatory modules at each time point, to identify key regulators driving changes of the cellular state, and to causally connect the modules across different time points. We applied the method to analyze paired chromatin accessibility and gene expression data from a retinoic acid (RA)–induced mouse embryonic stem cells (mESCs) differentiation experiment. The analysis identified 57,048 novel regulatory elements regulating cerebellar development, synapse assembly, and hindbrain morphogenesis, which substantially extended our knowledge of cis -regulatory elements during differentiation. Using single-cell RNA-seq data, we showed that the core regulatory modules can reflect the properties of different subpopulations of cells. Finally, the driver regulators are shown to be important in clarifying the relations between modules across adjacent time points. As a second example, our method on Ascl1 -induced direct reprogramming from fibroblast to neuron time course data identified Id1/2 as driver regulators of early stage of reprogramming.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2020
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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