Protein complexes are central in the yeast genetic landscape.
Protein complexes are central in the yeast genetic landscape.
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DOI：
10.1371/journal.pcbi.1001092
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发表时间：
2011-02
影响因子：
4.3
通讯作者：
Bader GD
中科院分区：
文献类型：
--
作者：
Michaut M;Baryshnikova A;Costanzo M;Myers CL;Andrews BJ;Boone C;Bader GD
如果两个基因的干扰比预期的效果更强或更弱，它们就被称为基因相互作用。遗传相互作用很重要，因为它们有助于绘制基因功能图，功能相关的基因具有相似的遗传相互作用模式。最近，在全球范围内绘制定量（积极和消极）遗传相互作用已成为可能。这些数据清楚地显示了由主要的正或负相互作用连接的基因组，称为单色组。这些组通常对应于功能模块，如生物过程或复合体，或模块之间的连接。然而，目前还不知道这些模式如何全局地与已知的功能模块相关。在这里，我们系统地研究单色性已知的生物过程中使用最大的定量遗传相互作用的数据集，其中包括健身测量540万个基因对的酵母酿酒酵母。我们发现，只有10%的生物过程，如基因本体论注释所定义的，只有不到1%的过程间连接是单色的。此外，我们表明，蛋白质复合物是负责这些模式的一个令人惊讶的大部分。这表明复合体在塑造生物过程的单色景观方面发挥着核心作用。总之，这项工作表明，积极和消极的单色模式中发现已知的生物过程和它们的连接，蛋白质复合物在这些模式中发挥重要作用。我们发现的单色过程，复合物和连接绘制了酵母细胞中敏感和冗余生物系统的分层和模块化地图，这将有助于基因功能预测和表型和生物体之间的比较。此外，我们开发的分析方法也适用于其他物种，这些物种的遗传相互作用将逐渐变得更加可用。遗传互作反映了基因间的功能依赖关系，是预测基因功能的有力工具。功能相关的基因往往具有相似的遗传相互作用谱。最近，全球规模的定量（积极和消极）遗传相互作用的映射已经完成。这些数据清楚地显示了由主要的正或负相互作用连接的基因组，称为单色组。这些组通常对应于功能模块，如生物过程或蛋白质复合物，或模块之间的连接，但目前还不知道这些模式如何全局地与已知的功能模块相关。在这里，我们系统地评估单色的性质，已知的生物过程和它们的连接在酵母酿酒酵母。我们发现，10%的生物过程和不到1%的过程间连接是单色的。此外，我们表明，蛋白质复合物是负责这些单色组的一个令人惊讶的大部分。我们发现的单色过程，复合物和连接绘制了酵母细胞中敏感和冗余生物系统的分层和模块化地图，这将有助于基因功能预测和表型和生物体之间的比较。
If perturbing two genes together has a stronger or weaker effect than expected, they are said to genetically interact. Genetic interactions are important because they help map gene function, and functionally related genes have similar genetic interaction patterns. Mapping quantitative (positive and negative) genetic interactions on a global scale has recently become possible. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, like biological processes or complexes, or connections between modules. However it is not yet known how these patterns globally relate to known functional modules. Here we systematically study the monochromatic nature of known biological processes using the largest quantitative genetic interaction data set available, which includes fitness measurements for ∼5.4 million gene pairs in the yeast Saccharomyces cerevisiae. We find that only 10% of biological processes, as defined by Gene Ontology annotations, and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these patterns. This suggests that complexes play a central role in shaping the monochromatic landscape of biological processes. Altogether this work shows that both positive and negative monochromatic patterns are found in known biological processes and in their connections and that protein complexes play an important role in these patterns. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms. Furthermore the analysis methods we develop are applicable to other species for which genetic interactions will progressively become more available. Genetic interactions indicate functional dependencies between genes and are a powerful tool to predict gene function. Functionally related genes tend to have similar profiles of genetic interactions. Recently, global scale mapping of quantitative (positive and negative) genetic interactions has been performed. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, such as biological processes or protein complexes, or connections between modules, but it is not yet known how these patterns globally relate to known functional modules. Here we systematically evaluate the monochromatic nature of known biological processes and their connections in the yeast Saccharomyces cerevisiae. We find that 10% of biological processes and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these monochromatic groups. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms.
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DOI：
10.1093/bioinformatics/btq197
发表时间：
2010-06-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Jaimovich A;Rinott R;Schuldiner M;Margalit H;Friedman N
通讯作者：
Friedman N
DOI：
10.1073/pnas.0712255105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Mani, Ramamurthy;Onge, Robert P. St.;Roth, Frederick P.
通讯作者：
Roth, Frederick P.
影响因子：
56.9
作者：
Hillenmeyer, Maureen E.;Fung, Eula;Giaever, Guri
通讯作者：
Giaever, Guri
在基因组量表上对酵母中适应性和遗传相互作用的定量分析。
影响因子：
48
作者：
Baryshnikova, Anastasia;Costanzo, Michael;Kim, Yungil;Ding, Huiming;Koh, Judice;Toufighi, Kiana;Youn, Ji-Young;Ou, Jiongwen;San Luis, Bryan-Joseph;Bandyopadhyay, Sunayan;Hibbs, Matthew;Hess, David;Gingras, Anne-Claude;Bader, Gary D.;Troyanskaya, Olga G.;Brown, Grant W.;Andrews, Brenda;Boone, Charles;Myers, Chad L.
通讯作者：
Myers, Chad L.
影响因子：
12.3
作者：
Collins SR;Schuldiner M;Krogan NJ;Weissman JS
通讯作者：
Weissman JS