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Centre for Statistics (CENSTAT) : project R-5464

Title : Differential splicing detection in early drug developments experiments. (R-5464)
Abstract: Thousands of human genes contain hundreds of thousands of exons, which produce hundreds of thousands of different transcript isoforms. The recent advance in genomics such as Affymetrix Exon ST and Human Transcriptome Arrays offer huge potential for whole genome investigation of differential splicing detections. However, such potential is limited partly due to limited number of advance statistical methodology for differential splicing detections. This proposed PhD focuses on both the advance methodology development for differential splicing detection and the application of the methodology in early drug development experiments. The proposed methodology development is based on a mixed model frame work, which provides natural framework for differential splicing detection. The fixed effect of the mixed model corresponds to the gene effects while the random components denotes individual exon deviation from the associated gene expression profile. The magnitudes of exon deviation from the expression of their associated genes is a good indication of whether the gene contains differentially spliced exons or not. This PhD study also covers the extensive analysis of in-house and publicly available experiments on splice variants as well as grouping the detected differential splicing according the most likely splicing mechanisms. This project reveals the science of splice variants and their potential as therapeutic targets and biomarkers.
Period of project : 1/10/2014to30/09/2018

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