Imputing and predicting quantitative genetic interactions in epistatic MAPs.

Mapping epistatic (or genetic) interactions has emerged as an important network biology approach for establishing functional relationships among genes and proteins. Epistasis networks are complementary to physical protein interaction networks, providing valuable insight into both the function of individual genes and the overall wiring of the cell. A high-throughput method termed "epistatic mini array profiles" (E-MAPs) was recently developed in yeast to quantify alleviating or aggravating interactions between gene pairs. The typical output of an E-MAP experiment is a large symmetric matrix of interaction scores. One problem with this data is the large amount of missing values - interactions that cannot be measured during the high-throughput process or whose measurements were discarded due to quality filtering steps. These missing values can reduce the effectiveness of some data analysis techniques and prevent the use of others. Here, we discuss one solution to this problem, imputation using nearest neighbors, and give practical examples of the use of a freely available implementation of this method.

[1]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Russ B. Altman,et al.  Missing value estimation methods for DNA microarrays , 2001, Bioinform..

[3]  Shin Ishii,et al.  A Bayesian missing value estimation method for gene expression profile data , 2003, Bioinform..

[4]  T. H. Bø,et al.  LSimpute: accurate estimation of missing values in microarray data with least squares methods. , 2004, Nucleic acids research.

[5]  S. L. Wong,et al.  Combining biological networks to predict genetic interactions. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Sean R. Collins,et al.  A strategy for extracting and analyzing large-scale quantitative epistatic interaction data , 2006, Genome Biology.

[7]  T. Ideker,et al.  Systematic interpretation of genetic interactions using protein networks , 2005, Nature Biotechnology.

[8]  Sean R. Collins,et al.  Exploration of the Function and Organization of the Yeast Early Secretory Pathway through an Epistatic Miniarray Profile , 2005, Cell.

[9]  Gene H. Golub,et al.  Missing value estimation for DNA microarray gene expression data: local least squares imputation , 2005, Bioinform..

[10]  A. Fraser,et al.  Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways , 2006, Nature Genetics.

[11]  Nevan J Krogan,et al.  High-throughput genetic interaction mapping in the fission yeast Schizosaccharomyces pombe , 2007, Nature Methods.

[12]  Tero Aittokallio,et al.  Missing value imputation improves clustering and interpretation of gene expression microarray data , 2008, BMC Bioinformatics.

[13]  Sean R. Collins,et al.  A tool-kit for high-throughput, quantitative analyses of genetic interactions in E. coli , 2008, Nature Methods.

[14]  Ambuj K. Singh,et al.  Predicting genetic interactions with random walks on biological networks , 2009, BMC Bioinformatics.

[15]  Shan Zhao,et al.  Mining protein networks for synthetic genetic interactions , 2008, BMC Bioinformatics.

[16]  J. Bader,et al.  Finding friends and enemies in an enemies-only network: a graph diffusion kernel for predicting novel genetic interactions and co-complex membership from yeast genetic interactions. , 2008, Genome research.

[17]  R. Shamir,et al.  Towards accurate imputation of quantitative genetic interactions , 2009, Genome Biology.

[18]  Derek Greene,et al.  Missing value imputation for epistatic MAPs , 2010, BMC Bioinformatics.

[19]  Nevan J Krogan,et al.  Quantitative genetic interaction mapping using the E-MAP approach. , 2010, Methods in enzymology.

[20]  G. Fink,et al.  Guide to yeast genetics : functional genomics, proteomics, and other systems analysis , 2010 .