Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection
Cheng Li,Wing Hung Wong +1 more
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TLDR
A statistical model is proposed for the probe-level data, and model-based estimates for gene expression indexes are developed, which help to identify and handle cross-hybridizing probes and contaminating array regions.Abstract:
Recent advances in cDNA and oligonucleotide DNA arrays have made it possible to measure the abundance of mRNA transcripts for many genes simultaneously. The analysis of such experiments is nontrivial because of large data size and many levels of variation introduced at different stages of the experiments. The analysis is further complicated by the large differences that may exist among different probes used to interrogate the same gene. However, an attractive feature of high-density oligonucleotide arrays such as those produced by photolithography and inkjet technology is the standardization of chip manufacturing and hybridization process. As a result, probe-specific biases, although significant, are highly reproducible and predictable, and their adverse effect can be reduced by proper modeling and analysis methods. Here, we propose a statistical model for the probe-level data, and develop model-based estimates for gene expression indexes. We also present model-based methods for identifying and handling cross-hybridizing probes and contaminating array regions. Applications of these results will be presented elsewhere.read more
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Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
TL;DR: The hierarchical model of Lonnstedt and Speed (2002) is developed into a practical approach for general microarray experiments with arbitrary numbers of treatments and RNA samples and the moderated t-statistic is shown to follow a t-distribution with augmented degrees of freedom.
Journal ArticleDOI
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Rafael A. Irizarry,Bridget G. Hobbs,Francois Collin,Yasmin Beazer-Barclay,Kristen J. Antonellis,Uwe Scherf,Terence P. Speed +6 more
TL;DR: There is no obvious downside to using RMA and attaching a standard error (SE) to this quantity using a linear model which removes probe-specific affinities, and the exploratory data analyses of the probe level data motivate a new summary measure that is a robust multi-array average (RMA) of background-adjusted, normalized, and log-transformed PM values.
Journal ArticleDOI
Summaries of Affymetrix GeneChip probe level data
Rafael A. Irizarry,Benjamin M. Bolstad,Francois Collin,Leslie Cope,Bridget G. Hobbs,Terence P. Speed,Terence P. Speed +6 more
TL;DR: It is found that the performance of the current version of the default expression measure provided by Affymetrix Microarray Suite can be significantly improved by the use of probe level summaries derived from empirically motivated statistical models.
Journal ArticleDOI
affy---analysis of Affymetrix GeneChip data at the probe level
TL;DR: The affy package is an R package of functions and classes for the analysis of oligonucleotide arrays manufactured by Affymetrix that provides the user with extreme flexibility when carrying out an analysis and make it possible to access and manipulate probe intensity data.
References
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PatentDOI
Expression monitoring by hybridization to high density oligonucleotide arrays
TL;DR: In this article, the authors proposed a method for monitoring the expression levels of a multiplicity of genes by hybridizing a nucleic acid sample to a high density array of oligonucleotide probes and quantifying the hybridized nucleic acids in the array.
Journal ArticleDOI
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Journal ArticleDOI
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High density synthetic oligonucleotide arrays
TL;DR: An approach in which sequence information is used directly to design high–density, two–dimensional arrays of synthetic oligonucleotides is developed, which have been designed and used for quantitative and highly parallel measurements of gene expression, to discover polymorphic loci and to detect the presence of thousands of alternative alleles.
Journal ArticleDOI
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