An emerging theme from large-scale genetic screens that identify genes essential for fitness of a cell, is that essentiality of a given gene is highly context-specific and depends on a number of genetic and environmental factors. Identification of such contexts could be the key to defining the function of the gene and also to develop novel therapeutic interventions. Here we present CEN-tools (Context-specific Essentiality Network-tools), a website and an accompanying python package, in which users can interrogate the essentiality of a gene from large-scale genome-scale CRISPR screens in a number of biological contexts including tissue of origin, mutation profiles, expression levels, and drug response levels. We show that CEN-tools is suitable for both the systematic identification of genetic dependencies as well as for targeted queries into the dependencies of specific user-selected genes. The associations between genes and a given context within CEN-tools are represented as dependency networks (CENs) and we demonstrate the utility of these networks in elucidating novel gene functions. In addition, we integrate the dependency networks with existing protein-protein interaction networks to reveal context-dependent essential cellular pathways in cancer cells. Together, we demonstrate the applicability of CEN-tools in aiding the current efforts to define the human cellular dependency map.

中文翻译：

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CEN-tools：鉴定必需基因的“背景”的综合平台

大规模遗传筛选的一个新兴主题是确定对细胞适应性至关重要的基因，即给定基因的重要性与环境密切相关，并取决于许多遗传和环境因素。鉴定此类环境可能是定义基因功能以及开发新的治疗干预措施的关键。在这里，我们目前CEN-工具（ç ontext特定è ssentiality ñetwork-tools），一个网站和一个随附的python软件包，用户可以在许多生物学环境中从大规模基因组规模的CRISPR筛选中询问基因的本质，包括起源组织，突变谱，表达水平和药物反应水平。我们表明，CEN工具既适用于遗传依赖性的系统识别，也适用于针对特定用户选择基因的依赖性的有针对性的查询。CEN工具内的基因与给定上下文之间的关联表示为依赖网络（CEN），我们证明了这些网络在阐明新型基因功能中的实用性。此外，我们将依赖关系网络与现有的蛋白质-蛋白质相互作用网络相结合，以揭示癌细胞中上下文相关的基本细胞途径。一起，