Methods for genome-wide screening and construction of genetic interaction maps

    公开(公告)号:US10144927B2

    公开(公告)日:2018-12-04

    申请号:US14458114

    申请日:2014-08-12

    摘要: The present invention provides methods for conducting screens using nucleic acid elements (e.g., interfering RNAs) to confidently identify hit genetic elements. The present invention further comprises constructing vectors that contain two or more nucleic acid elements to knock down all pairwise combinations of the hit genetic elements identified from the screen. Following quantitation of the single and double-knockdown phenotypes, genetic interactions between all gene pairs can be calculated. Genes can then be clustered according to the similarity of the pattern of their interactions with all of the other genes to obtain a genetic interaction map, which can advantageously be used to predict functional associations between genes and identify drug targets for therapy such as combination cancer therapy.

    METHODS FOR GENOME-WIDE SCREENING AND CONSTRUCTION OF GENETIC INTERACTION MAPS
    6.
    发明申请
    METHODS FOR GENOME-WIDE SCREENING AND CONSTRUCTION OF GENETIC INTERACTION MAPS 审中-公开
    广泛筛选和遗传相互作用的构建方法

    公开(公告)号:US20150072893A1

    公开(公告)日:2015-03-12

    申请号:US14458114

    申请日:2014-08-12

    IPC分类号: C12N15/10 G06F19/18

    摘要: The present invention provides methods for conducting screens using nucleic acid elements (e.g., interfering RNAs) to confidently identify hit genetic elements. The present invention further comprises constructing vectors that contain two or more nucleic acid elements to knock down all pairwise combinations of the hit genetic elements identified from the screen. Following quantitation of the single and double-knockdown phenotypes, genetic interactions between all gene pairs can be calculated. Genes can then be clustered according to the similarity of the pattern of their interactions with all of the other genes to obtain a genetic interaction map, which can advantageously be used to predict functional associations between genes and identify drug targets for therapy such as combination cancer therapy.

    摘要翻译: 本发明提供了使用核酸元件(例如干扰RNA)进行筛选以自信地鉴定命中遗传元件的方法。 本发明还包括构建含有两个或更多个核酸元件的载体,以压倒从屏幕识别的命中遗传元件的所有成对组合。 在定量单次和双重敲除表型后,可以计算所有基因对之间的遗传相互作用。 然后可以根据其与所有其他基因的相互作用模式的相似性将基因聚类,以获得遗传相互作用图,其可有利地用于预测基因之间的功能关联并鉴定用于治疗的药物靶标,例如组合癌症治疗 。