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Quantitative maps of genetic interactions in yeast - Comparative evaluation and integrative analysis

DOI: 10.1186/1752-0509-5-45

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Abstract:

Using large-scale data matrices from epistatic miniarray profiling (E-MAP), genetic interaction mapping (GIM), and synthetic genetic array (SGA) approaches, we carried out here a systematic comparative evaluation among these quantitative maps of genetic interactions in yeast. The relatively low association between the original interaction measurements or their customized scores could be improved using a matrix-based modelling framework, which enables the use of single- and double-mutant fitness estimates and measurements, respectively, when scoring genetic interactions. Toward an integrative analysis, we show how the detections from the different screening approaches can be combined to suggest novel positive and negative interactions which are complementary to those obtained using any single screening approach alone. The matrix approximation procedure has been made available to support the design and analysis of the future screening studies.We have shown here that even if the correlation between the currently available quantitative genetic interaction maps in yeast is relatively low, their comparability can be improved by means of our computational matrix approximation procedure, which will enable integrative analysis and detection of a wider spectrum of genetic interactions using data from the complementary screening approaches.The recent advances in experimental biotechnologies have made it possible to start screening genome-wide datasets of quantitative genetic interactions in model organisms such as yeast [1-3]. High-throughput genetic screening approaches, such as those based on epistatic miniarray profiling (E-MAP) [4-7], genetic interaction mapping (GIM) [8], and synthetic genetic array (SGA) [9-11], have provided systematic means to global investigation of quantitative relationship between genotype and phenotype, with potential implications for a wide range of biological phenomena, including, for instance, modularity, essentiality, redundancy, buffering, epi

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