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METHOD FOR IDENTIFICATION OF ACTIVATED molecular mechanisms specific to carcinogenesis in individual patients, and to generate personalized recommendations for optimization SCHEMES antitumor pharmacotherapy

机译:识别个体患者致癌作用的特定激活分子机制的方法,并为优化SCHEMES抗肿瘤药物治疗产生个性化建议

摘要

A method for identifying activated molecular mechanisms that are specific for carcinogenesis process in the individual patient, and generating personalized recommendations for optimization schemes anticancer drug therapy, comprising the following steps: a) search the activated gene regulatory network consisting of a central controller (such as a transcription factor) and regulated genes using data RNASeq-tumor tissue and standards using SNEA algorithm; b) made the union found genetic regulatory etey into clusters based on similarity of a set of regulated genes using measure Jaccard and hierarchical clustering method Ward, wherein each cluster controllers attributed measure characterizing the level of expression of components of the cluster of genes and defined as the sum in the cluster medians regulated gene expression changes; c) case of simultaneous analysis of multiple samples using cluster analysis (using Pearson correlation and Ward method) defined groups of patients with similar profiles acti th e signaling pathways controls and the patient is assigned to the closest group to allow for additional clinical information, in particular on the sensitivity / resistance to specific therapy; g) search for genetic regulatory networks and canonical signaling pathways significantly enriched with differentially expressed genes and genes with mutations (single nucleotide polymorphisms, and insertions / substitutions found by ekzomnym data), the more weight can be assigned to polymorphisms in the gene regulators eq
机译:一种用于识别个体患者致癌过程特异的激活分子机制,并为优化方案抗癌药物治疗生成个性化推荐的方法,该方法包括以下步骤:a)搜索由中央控制器(例如转录因子)和调控的基因,使用数据RNASeq肿瘤组织和标准品(使用SNEA算法); b)使用测量Jaccard和层次聚类方法Ward,根据一组受调控基因的相似性,使工会找到了遗传调控基因,将每个聚类控制器归为代表基因聚类成分表达水平的度量,并定义为簇中位数调节基因表达变化的总和; c)使用聚类分析(使用Pearson相关和Ward方法)同时分析多个样品的情况,这些组定义了具有相似特征的患者组,这些组是激活信号通路的对照,并且将患者分配到最接近的组中,以提供更多的临床信息。特别是对特定疗法的敏感性/耐药性; g)寻找遗传调控网络和规范信号通路,其中显着地丰富了差异表达的基因和具有突变的基因(单核苷酸多态性,以及由ekzomnym数据发现的插入/替换),在基因调节器eq中可以赋予多态性更多的权重

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