系统地使用计算方法可以对多形性胶质母细胞瘤的治疗反应进行分层

R. Louhimo, V. Aittomäki, A. Faisal, M. Laakso, Ping Chen, K. Ovaska, E. Valo, L. Lahti, V. Rogojin, Samuel Kaski, S. Hautaniemi
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引用次数: 0

摘要

背景:癌症是一种复杂的疾病,其综合表征需要从遗传学到转录组学和临床数据等多个水平的基因组级分子数据。利用我们最近发表的Anduril生物信息学框架和新的计算方法,如依赖性分析,我们确定了多形性胶质母细胞瘤(GBM)进展和耐药性中的miRNA、拷贝数变化、表达、甲基化和途径水平的关键变量。此外,我们确定了临床相关亚组的特征,例如接受替莫唑胺治疗的患者和EGFRvIII突变的患者,EGFRvIII突变是EGFR的组成型活性变体。结果:我们确定了几个新的基因组区域和转录谱,可能有助于GBM的进展和耐药性。所有结果和Anduril脚本可在http://csbi.ltdk.helsinki.fi/camda/上获得。结论:我们的研究结果强调需要在多个水平上定义上下文的方法,以确定在癌症进展和耐药性中起关键作用的基因组区域或转录谱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Systematic use of computational methods allows stratification of treatment responders in glioblastoma multiforme
Background: Cancers are complex diseases whose comprehensive characterization requires genome-scale molecular data at multiple levels from genetics to transcriptomics and clinical data. Using our recently published Anduril bioinformatics framework and novel computational approaches, such as dependency analysis, we identify key variables at miRNA, copy number variation, expression, methylation, and pathway levels in glioblastoma multiforme (GBM) progression and drug resistance. Furthermore, we identify characteristics of clinically relevant subgroups, such as patients treated with temozolomide and patients with an EGFRvIII mutation, which is a constitutively active variant of EGFR. Results: We identify several novel genomic regions and transcript profiles that may contribute to GBM progression and drug resistance. All results and Anduril scripts are available at http://csbi.ltdk.helsinki.fi/camda/. Conclusions: Our results highlight the need for approaches that define context at several levels in order to identify genomic regions or transcript profiles playing key roles in cancer progression and drug resistance.
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