Correlation Vectors in Gene Expression Profiling Modern methods of microarray data analysis are biased towards selecting those genes that display the most pronounced differential expression. Our preliminary studies strongly suggest that the correlation structure of microarray data can serve as an important indicator of changes in transcription profiles between phenotypes. The objective of the proposed project is to develop a new multivariate method for selecting candidate genes that change their relationships (correlations) with other genes across the conditions (phenotypes) under study. This will be accomplished by designing a pertinent multivariate statistical test and associated resampling algorithm. The proposed method represents a radical conceptual change in current approaches focused solely on differentially expressed genes. This new approach will enable the biologist to enrich currently practiced methods of microarray data analysis with quantitative inference on dependencies between gene expression intensities. An efficient multiple testing rule will be designed to combine the two approaches in a single procedure that provides strong control of false discoveries. The proposed general methodology will provide biological investigators with an additional source of information, allowing them to make more educated decisions when selecting and prioritizing candidate genes from microarray data analysis. This methodology has far-reaching implications for diverse research activities in modern genomics that involve uncovering molecular mechanisms of diseases and finding therapeutic targets. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21GM079259-01A1
Application #
7291808
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Li, Jerry
Project Start
2007-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$154,000
Indirect Cost
Name
University of Rochester
Department
Biostatistics & Other Math Sci
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Qiu, Xing; Klebanov, Lev (2013) Gene selection with the ýý-sequence method. Methods Mol Biol 972:57-71
Needham, Mark; Hu, Rui; Dwarkadas, Sandhya et al. (2011) Hierarchical parallelization of gene differential association analysis. BMC Bioinformatics 12:374
Hu, Rui; Qiu, Xing; Glazko, Galina (2010) A new gene selection procedure based on the covariance distance. Bioinformatics 26:348-54
Glazko, Galina V; Emmert-Streib, Frank (2009) Unite and conquer: univariate and multivariate approaches for finding differentially expressed gene sets. Bioinformatics 25:2348-54
Hanin, Leonid; Awadalla, Saria S; Cox, Paul et al. (2009) Chromosome-specific spatial periodicities in gene expression revealed by spectral analysis. J Theor Biol 256:333-42
Hu, Rui; Qiu, Xing; Glazko, Galina et al. (2009) Detecting intergene correlation changes in microarray analysis: a new approach to gene selection. BMC Bioinformatics 10:20
Klebanov, Lev B; Yakovlev, Andrei Yu (2008) A nitty-gritty aspect of correlation and network inference from gene expression data. Biol Direct 3:35
Klebanov, Lev; Chen, Linlin; Yakovlev, Andrei (2007) Revisiting adverse effects of cross-hybridization in Affymetrix gene expression data: do they matter for correlation analysis? Biol Direct 2:28
Klebanov, Lev; Glazko, Galina; Salzman, Peter et al. (2007) A multivariate extension of the gene set enrichment analysis. J Bioinform Comput Biol 5:1139-53