Methods for enhanced detection and analysis of...

Data processing: measuring – calibrating – or testing – Measurement system in a specific environment – Biological or biochemical

Reexamination Certificate

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C435S006120

Reexamination Certificate

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07454293

ABSTRACT:
A method for enhanced detection and statistical analysis of differentially expressed genes in gene chip microarrays employs: (a) transformation of gene expression data into an expression data matrix (image data paradigm); (b) wavelet denoising of expression data matrix values to enhance their signal-to-noise ratio; and (c) singular value decomposition (SVD) of the wavelet-denoised expression data matrix to concentrate most of the gene expression signal in primary matrix eigenarrays to enhance the separation of true gene expression values from background noise. The transformation of gene chip data into an image data paradigm facilitates the use of powerful image data processing techniques, including a generalized logarithm (g-log) function to stabilize variance over intensity, and the WSVD combination of wavelet packet transform and denoising and SVD to clearly enhance separation of the truly changed genes from background noise. Detection performance can be assessed using a true false discovery rate (tFDR) computed for simulated gene expression data, and comparing it to estimated FDR (eFDR) rates based on permutations of the available data. Where a small number (N) of samples in a group is involved, a pair of specific WSVD algorithms are employed complementarily if N>5 and if N<6.

REFERENCES:
patent: 6351712 (2002-02-01), Stoughton et al.
patent: 2002/0019704 (2002-02-01), Tusher
patent: WO 02/057426 (2002-07-01), None
Morgan et al. Frequent sampling reveals Dynamic responses by the Transcriptome to Routine Media replacement in HepG2 Cells. Toxicologic Pathology vol. 31, pp. 448-461 (2003).
Klevecz et al, “Genome Wide Oscillations in Expression”, Mol.Biol. Rpts. 2001, vol. 28, p. 73-82.
Morgan et al, “Frequent Sampling Reveals Dynamic Responses by the Transcriptome . . . ”, Toxicologic Path. 2003, vol. 31, p. 448-461.

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