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  1. Article ; Online: 2023 ASHG Scientific Achievement Award: Molly Przeworski.

    Shendure, Jay

    American journal of human genetics

    2024  Volume 111, Issue 3, Page(s) 424

    Abstract: This article is based on the address given by the author at the 2023 meeting of The American Society of Human Genetics (ASHG) in Washington, D.C. The video of the original address can be found at the ASHG website. ...

    Abstract This article is based on the address given by the author at the 2023 meeting of The American Society of Human Genetics (ASHG) in Washington, D.C. The video of the original address can be found at the ASHG website.
    MeSH term(s) United States ; Humans ; Animals ; Genetics, Medical ; Societies, Scientific ; Poecilia ; Awards and Prizes
    Language English
    Publishing date 2024-03-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 219384-x
    ISSN 1537-6605 ; 0002-9297
    ISSN (online) 1537-6605
    ISSN 0002-9297
    DOI 10.1016/j.ajhg.2023.12.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 107: Show issues Location:
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  2. Article ; Online: A reference cell tree will serve science better than a reference cell atlas.

    Domcke, Silvia / Shendure, Jay

    Cell

    2023  Volume 186, Issue 6, Page(s) 1103–1114

    Abstract: Single-cell biology is facing a crisis of sorts. Vast numbers of single-cell molecular profiles are being generated, clustered and annotated. However, this is overwhelmingly ad hoc, and we continue to lack a principled, unified, and well-moored system ... ...

    Abstract Single-cell biology is facing a crisis of sorts. Vast numbers of single-cell molecular profiles are being generated, clustered and annotated. However, this is overwhelmingly ad hoc, and we continue to lack a principled, unified, and well-moored system for defining, naming, and organizing cell types. In this perspective, we argue against an atlas or periodic table-like discretization as the right metaphor for a reference taxonomy of cell types. In its place, we advocate for a data-driven, tree-based nomenclature that is rooted in a "consensus ontogeny" spanning the life cycle of a given species. We explore how such a reference cell tree, inclusive of both lineage histories and molecular states, could be constructed, represented, and segmented in practice. Analogous to the taxonomic classification of species, a consensus ontogeny would provide a universal, stable, and extendable framework for precise scientific communication, both contemporaneously and across the ages.
    MeSH term(s) Communication ; Cytology ; Life Cycle Stages ; Phylogeny ; Single-Cell Analysis
    Language English
    Publishing date 2023-03-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2023.02.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A molecular proximity sensor based on an engineered, dual-component guide RNA.

    Choi, Junhong / Chen, Wei / Liao, Hanna / Li, Xiaoyi / Shendure, Jay

    bioRxiv : the preprint server for biology

    2024  

    Abstract: One of the goals of synthetic biology is to enable the design of arbitrary molecular circuits with programmable inputs and outputs. Such circuits bridge the properties of electronic and natural circuits, processing information in a predictable manner ... ...

    Abstract One of the goals of synthetic biology is to enable the design of arbitrary molecular circuits with programmable inputs and outputs. Such circuits bridge the properties of electronic and natural circuits, processing information in a predictable manner within living cells. Genome editing is a potentially powerful component of synthetic molecular circuits, whether for modulating the expression of a target gene or for stably recording information to genomic DNA. However, programming molecular events such as protein-protein interactions or induced proximity as triggers for genome editing remains challenging. Here we demonstrate a strategy termed "P3 editing", which links protein-protein proximity to the formation of a functional CRISPRCas9 dual-component guide RNA. By engineering the crRNA:tracrRNA interaction, we demonstrate that various known protein-protein interactions, as well as the chemically-induced dimerization of protein domains, can be used to activate prime editing or base editing in human cells. Additionally, we explore how P3 editing can incorporate outputs from ADAR-based RNA sensors, potentially allowing specific RNAs to induce specific genome edits within a larger circuit. Our strategy enhances the controllability of CRISPR-based genome editing, facilitating its use in synthetic molecular circuits deployed in living cells.
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.14.553235
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A continuous model of early mammalian development.

    Qiu, Chengxiang / Shendure, Jay

    Nature

    2021  Volume 593, Issue 7858, Page(s) 200–201

    MeSH term(s) Animals ; Embryo, Mammalian ; Mammals
    Language English
    Publishing date 2021-04-28
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-021-01153-1
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    Zs.A 26: Show issues Location:
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    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

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  5. Article ; Online: Genetic Tools for Cell Lineage Tracing and Profiling Developmental Trajectories in the Skin.

    Nathans, Jenny F / Ayers, Jessica L / Shendure, Jay / Simpson, Cory L

    The Journal of investigative dermatology

    2024  Volume 144, Issue 5, Page(s) 936–949

    Abstract: The epidermis is the body's first line of protection against dehydration and pathogens, continually regenerating the outermost protective skin layers throughout life. During both embryonic development and wound healing, epidermal stem and progenitor ... ...

    Abstract The epidermis is the body's first line of protection against dehydration and pathogens, continually regenerating the outermost protective skin layers throughout life. During both embryonic development and wound healing, epidermal stem and progenitor cells must respond to external stimuli and insults to build, maintain, and repair the cutaneous barrier. Recent advances in CRISPR-based methods for cell lineage tracing have remarkably expanded the potential for experiments that track stem and progenitor cell proliferation and differentiation over the course of tissue and even organismal development. Additional tools for DNA-based recording of cellular signaling cues promise to deepen our understanding of the mechanisms driving normal skin morphogenesis and response to stressors as well as the dysregulation of cell proliferation and differentiation in skin diseases and cancer. In this review, we highlight cutting-edge methods for cell lineage tracing, including in organoids and model organisms, and explore how cutaneous biology researchers might leverage these techniques to elucidate the developmental programs that support the regenerative capacity and plasticity of the skin.
    MeSH term(s) Humans ; Cell Lineage ; Animals ; Cell Differentiation ; Skin/cytology ; Stem Cells/cytology ; Cell Proliferation ; Regeneration/physiology
    Language English
    Publishing date 2024-04-22
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2024.02.006
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  6. Article ; Online: Human genomics: A deep dive into genetic variation.

    Shendure, Jay

    Nature

    2016  Volume 536, Issue 7616, Page(s) 277–278

    MeSH term(s) Genetic Variation ; Genomics ; Humans
    Language English
    Publishing date 2016--18
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/536277a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 244: Show issues

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  7. Article ; Online: Expanding the single-cell genomics toolkit.

    Minkina, Anna / Shendure, Jay

    Nature genetics

    2019  Volume 51, Issue 6, Page(s) 931–932

    MeSH term(s) Breast Neoplasms ; Chromatin ; Genomics ; Humans ; Software
    Chemical Substances Chromatin
    Language English
    Publishing date 2019-07-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-019-0429-4
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  8. Article: Multiplex generation and single cell analysis of structural variants in a mammalian genome.

    Pinglay, Sudarshan / Lalanne, Jean-Benoit / Daza, Riza M / Koeppel, Jonas / Li, Xiaoyi / Lee, David S / Shendure, Jay

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The functional consequences of structural variants (SVs) in mammalian genomes are challenging to study. This is due to several factors, including: 1) their numerical paucity relative to other forms of standing genetic variation such as single nucleotide ... ...

    Abstract The functional consequences of structural variants (SVs) in mammalian genomes are challenging to study. This is due to several factors, including: 1) their numerical paucity relative to other forms of standing genetic variation such as single nucleotide variants (SNVs) and short insertions or deletions (indels); 2) the fact that a single SV can involve and potentially impact the function of more than one gene and/or
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.22.576756
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Predicting mRNA Abundance Directly from Genomic Sequence Using Deep Convolutional Neural Networks.

    Agarwal, Vikram / Shendure, Jay

    Cell reports

    2020  Volume 31, Issue 7, Page(s) 107663

    Abstract: Algorithms that accurately predict gene structure from primary sequence alone were transformative for annotating the human genome. Can we also predict the expression levels of genes based solely on genome sequence? Here, we sought to apply deep ... ...

    Abstract Algorithms that accurately predict gene structure from primary sequence alone were transformative for annotating the human genome. Can we also predict the expression levels of genes based solely on genome sequence? Here, we sought to apply deep convolutional neural networks toward that goal. Surprisingly, a model that includes only promoter sequences and features associated with mRNA stability explains 59% and 71% of variation in steady-state mRNA levels in human and mouse, respectively. This model, termed Xpresso, more than doubles the accuracy of alternative sequence-based models and isolates rules as predictive as models relying on chromatic immunoprecipitation sequencing (ChIP-seq) data. Xpresso recapitulates genome-wide patterns of transcriptional activity, and its residuals can be used to quantify the influence of enhancers, heterochromatic domains, and microRNAs. Model interpretation reveals that promoter-proximal CpG dinucleotides strongly predict transcriptional activity. Looking forward, we propose cell-type-specific gene-expression predictions based solely on primary sequences as a grand challenge for the field.
    MeSH term(s) Animals ; Genomics/methods ; Humans ; Mice ; Nerve Net ; RNA, Messenger/genetics
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2020-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.107663
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Life after genetics.

    Shendure, Jay

    Genome medicine

    2014  Volume 6, Issue 10, Page(s) 86

    Abstract: Gene finding is a finite exercise, and a means to an end, rather than an end in itself. The field of human genetics should increasingly shift its attention from disease gene identification to following through on next steps, most importantly pursuing the ...

    Abstract Gene finding is a finite exercise, and a means to an end, rather than an end in itself. The field of human genetics should increasingly shift its attention from disease gene identification to following through on next steps, most importantly pursuing the biological mechanisms underlying genotype-phenotype associations.
    Language English
    Publishing date 2014
    Publishing country England
    Document type Journal Article
    ZDB-ID 2484394-5
    ISSN 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-014-0086-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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