Showing 10 of 46348 results

  • PROJ Cytosine base editor generates substantial off-target single nucleotide variants in mouse embryos

    Yang Hui, Institute of Neuroscience, State Key Laboratory of Neuroscience,2018.11.30

    Description

    Genome editing holds promise for correcting pathogenic mutations. However, it is difficult to determine off-target effects of editing due to single-nucleotide polymorphism in individuals. Here we developed a method named GOTI (genome-wide off-target analysis by two-cell embryo injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. Comparison of the whole-genome sequences of progeny cells of edited and nonedited blastomeres at embryonic day 14.5 showed that off-target single-nucleotide variants (SNVs) were rare in embryos edited by CRISPR-Cas9 or adenine base editor, with a frequency close to the spontaneous mutation rate. By contrast, cytosine base editing induced SNVs at more than 20-fold higher frequencies, requiring a solution to address its fidelity. 

    OEP000195 Public

  • PROJ mGMB (mouse gut microbial biobank)

    Liu Chang, Institute of Microbiology, Chinese Academy of Science,2019.01.04

    Description

    To constructed a metabolic-syndrome-specific gut microbial biobank of ob/ob mouse, extensive bacterial isolatation, cultivation and preservation were performed. For each species, the draft genome of the representative strain was sequenced and provided in this bioproject 

    OEP000211 Public

  • PROJ 10X genomics human and mouse test data

    Xin Changpeng, PICB,2019.01.10

    Description

    test the 10X genomics system with human 293T and mouse 3T3 mixed cells 

    OEP000215 Public

  • PROJ Structure and degradation of circular RNAs regulate PKR activation in innate immunity

    Yang Li, CAS-MPG Partner Institute for Computational Biology,2019.01.19

    Description

    CircRNAs produced from back-splicing of exons of pre-mRNAs are widely expressed, but current understanding of their functions is limited. These RNAs are stable in general and are thought to have unique structural conformations distinct from their linear RNA cognates. Here we uncover that endogenous circRNAs tend to form 16-26 bp RNA duplexes and act as inhibitors of dsRNA-activated protein kinase (PKR) related to innate immunity. Upon poly(I:C) stimulation or viral infection, circRNAs are globally degraded by RNase L, a process required for PKR activation in early cellular innate immune responses. Augmented PKR phosphorylation and circRNA reduction are found in peripheral blood mononuclear cells (PBMCs) derived from patients of autoimmune disease systemic lupus erythematosus (SLE). Importantly, over-expression of the dsRNA-containing circRNA in PBMCs or T cells derived from SLE can alleviate the aberrant PKR activation cascade, thus providing a connection between circRNAs and SLE. 

    OEP000216 Public

  • PROJ A versatile baseediting tool withoutsequence preference for studying regulatory genomicelements

    Jiang Wen, ShanghaiTech University,2019.01.31

    Description

    Understanding the biology of functional genomic elements within non-coding regions is considered as one of the next frontiers of genomic studies.CRISPR-basedbase editing (BE)provides a tool to perturb genomic elements at single-nucleotide resolution. Yet, by comprehensive analysis of human genome, we found that “GC”dinucleotidesareenriched in regulatory regions, includingpromoter and the 5’UTR region. Furthermore, we and others found that currently available BEs displaya sequence preference, strongly disfavouring “GC” dinucleotides. To avoid such a sequence bias, we developed and characterized a new version of base editor, BE-PLUS(AID) without sequence preference, and use it to perform efficient and precise base editing at GC rich loci. Using BE-PLUS(AID), we successfully manipulated G-rich G-quadruplex (G4) elements and explored theirregulatory roles on gene expression.BE-PLUS(AID) will serve as a versatile tool for investigatingfunctional genomic elements. 

    OEP000222 Public

  • PROJ Xinyi_xBE3 and BPNLS-Gam-xBE3

    Liu Xinyi, Jinan university,2019.02.22

    Description

    Optimization of xBE3 and modeling pathogenic mutations in discarded human 3PN zygotes using BPNLS-Gam-xBE3. 

    OEP000252 Public

  • PROJ NG on cells and 3PN

    Liu Xinyi, Jinan university,2019.03.08

    Description

    targeted deep-sequencing raw data of BE-NG on 293T cells and discarded human 3PN zygotes 

    OEP000261 Public

  • PROJ Zfhx3 is required for the differentiation of late born D1-type medium spiny neurons

    feng hua, PICB,2019.03.11

    Description

     

    OEP000265 Public

  • PROJ Off-target RNA mutation induced by DNA base editing

    Yang Hui, Institute of Neuroscience, State Key Laboratory of Neuroscience,,2019.03.26

    Description

    Recently developed DNA base editing methods enable the direct generation of desired point mutations in genomic DNA without generating any double-strand breaks1,2,3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target mutations in genomic DNA4,5,6,7,8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9,10,11,12,13. For example, the cytosine deaminase APOBEC1—which is used in cytosine base editors (CBEs)—targets both DNA and RNA12, and the adenine deaminase TadA—which is used in adenine base editors (ABEs)—induces site-specific inosine formation on RNA9,11. However, any potential RNA mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA mutations induced by DNA base editors is of great concern14,15,16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases. 

    OEP000277 Public

  • PROJ MTSS1 Suppresses Expansion and Activity of Mammary Tumor-initiating Cells by Mediating P65 Ubiquitination and Degradation.

    Hu Guohong, SIBS,2019.03.28

    Description

    We conduct transcriptome comparison of control and Mtss1-overexpressed Py8119 cells to gain genomic insights on the biological processes that Mtss1 is involved in breast cancer cells. Through unsupervised cluster analysis of differentially expressed genes DEGs we found 1661 genes were significantly changed in Mtss1 cells. Single Site Analysis and Gene Set Enrichment Analysis show that Mtss1 downregualted numerous NF-κB targeted genes. 

    OEP000280 Public

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