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Biomedical subjects

Keng Wah Choo

Publications and source records attributed to Keng Wah Choo.

3 recordsLinked to original sources

Predicting single nucleotide polymorphisms (SNP) from DNA sequence by support vector machine.

Recently, SNP has gained substantial attention as genetic markers and is recognized as a key element in the development of personalized medicine. Computational prediction of SNP can be used as a guide for SNP discovery to reduce the cost and time needed for the development of personalized medicine. We have developed a method for SNP prediction based on support vector machines (SVMs) using different features extracted from the SNP data. Prediction rates of 60.9% was achieved by sequence feature, 59.1% by free-energy feature, 58.1% by GC content feature, 58.0% by melting temperature feature, 56.2% by enthalpy feature, 55.1% by entropy feature and 54.3% by the gene, exon and intron feature. We introduced a new feature, the SNP distribution score that achieved a prediction rate of 77.3%. Thus, the proposed SNP prediction algorithm can be used to in SNP discovery.

Algorithms↗

Identification of differentially expressed genes in multiple microarray experiments using discrete fourier transform.

Research in the post-genome sequence era has been shifting towards a functional understanding of the roles and relationships between different genes in different conditions. While the advances in genetic expression profiling techniques including microarrays enable detailed and genome-scale measurements, the extraction of meaningful information from large datasets remains a challenging task. Here, we propose a novel method of generating gene differential expression profiles such that gene expression values from one dataset can be directly compared with those of another dataset. A simplified Discrete Fourier Transform is applied to interposed gene expression values, thereby generating the 'spectra' for a pair of conditions. Using this technique, differentially expressed genes produce higher amplitudes at the Nyquist Frequency. By measuring the phase of the 'spectra' generated, the over- and under-expressed nature of the genes can be identified. This method was validated using two sets of GeneChip array data, one from prostate cancer related dataset and the other from macular degeneration related dataset. The genes identified as differentially expressed by our method were found to be similar to those published using their preferred methods. Based on our findings, the proposed DFT method could be used efficiently in identifying differentially expressed genes from multiple-array experiments from two different conditions.

Fourier Analysis↗

An isothermal method for whole genome amplification of fresh and degraded DNA for comparative genomic hybridization, genotyping and mutation detection.

Molecular genotyping has important biomedical and forensic applications. However, limiting amounts of human biological material often yield genomic DNA (gDNA) in insufficient quantity and of poor quality for a reliable analysis. This motivated the development of an efficient whole genome amplification method with quantitatively unbiased representation usable on fresh and degraded gDNA. Amplification of fresh frozen, formalin-fixed paraffin-embedded (FFPE) and DNase-degraded DNA using degenerate oligonucleotide-primed PCR or primer extension amplification using a short primer sequence bioinformatically optimized for coverage of the human genome was compared with amplification using current primers by chromosome-based and BAC-array comparative genomic hybridization (CGH), genotyping at short tandem repeats (STRs) and single base mutation detection. Compared with current primers, genome amplification using the bioinformatically optimized primer was significantly less biased on CGH in self-self hybridizations, and replicated tumour genome copy number aberrations, even from FFPE tissue. STR genotyping could be performed on degraded gDNA amplified using our technique but failed with multiple displacement amplification. Of the 18 different single base mutations 16 (89.5%) were correctly identified by sequencing gDNA amplified from clinical samples using our technique. This simple and efficient isothermal method should be helpful for genetic research and clinical and forensic applications.

Base Sequence↗