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science里程碑!花了15年,科学家“画出”首张细胞基因互作图谱时间:2016-10-11


      该研究由加拿大、美国、德国等多个国家的近20个研究单位的50多位科学家历时15年绘制完成。这是一张全新的细胞基因互作图谱,与之前报道过的图谱不同,这张新图谱首次展示了基因如何在细胞内以小组的形式相互作用,并解释了成千上万的基因在安排细胞生活的过程中如何互相协调,有望帮助阐明疾病的遗传根源,为探索基因如何导致疾病开辟了新的途径,有望帮助开发精准的治疗方法。

 

a global network of genetic interaction profile similarities.



      由于酵母细胞相对比较简单,而且酵母的6,000个基因中大多可以在人类中找到,因此,科学家们选择酵母来进行研究。对酵母细胞的研究表明,理解基因的作用不仅仅是研究它的个体效应。


      十多年前,在基因编辑技术尚不成熟的时候,他们首次一个接一个地删除了每一个酵母基因,结果发现,只有20%的基因是酵母生存所必须的。随着基因编辑技术的发展,直到去年科学家们才能够在人类细胞中进行相同的研究,并得到了相同的结果:只有一部分基因是人类细胞生存所必须的。


      这些研究结果表明,细胞中大多数基因只是发挥一种缓冲作用,以保护细胞免受突变和环境压力的伤害。


a global network of genetic interaction profile similarities. . (a) the essential similarity network was constructed by computing pccs for genetic interaction profiles (edges) of all pairs of genes (nodes) in the essential genetic interaction matrix (exe). gene pairs with profile similarity of pcc > 0.2 were connected and graphed using a spring-embedded layout algorithm. genes sharing similar genetic interaction profiles map proximal to each other, whereas genes with less similar genetic interaction profiles are positioned farther apart. (b) a genetic profile similarity network for the nonessential genetic interaction matrix (nxn). (c) a global genetic profile similarity network encompassing all nonessential and essential genes was constructed from the combined nxn, exe, and nxe genetic interaction matrices. (d) the essential similarity network was annotated using safe, identifying network regions enriched for similar go biological process terms, which are color-coded. (e) the nonessential similarity network annotated using safe. (f) the global similarity network annotated using safe.

      在这项新研究中,科学家们同时成对删除了2个基因,试图找到对酵母细胞生存至关重要的基因对。出于工作需要,他们定制了相应装置和最先进的流水线,分析了几乎所有1800万种不同的组合,最终鉴定出了酵母细胞中“共事”的基因对。  


      研究人员相信,人类疾病也应该有相关的基因对,而不是单个基因,这意味着新的研究计划可能需要对人类基因组中约2亿个可能的基因对进行深入分析。不过,在了解酵母图谱绘制方法的前提下,该方法能够用于不同细胞类型中的基因相互作用图谱,包括人类细胞。



gene function. (a) highly connected hub genes identified either as pleiotropic (blue nodes), or functionally specific (yellow nodes), are highlighted on a schematic representation of the global similarity network. examples of high (blue text) and low (yellow text) pleiotropy genes, grouped based on their general function, are shown. (b) poorly characterized genes that localize within, or in the vicinity of, a specific biological process–enriched cluster on the global similarity network. an estimated network position is indicated (*) for genes that are not present on the global similarity network because their genetic interaction profile similarity to other genes does not exceed a pcc > 0.2. network position for these genes was estimated as described .


(本文转自精准医学解读)


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