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PhD Lecture by Kai Wang, CBS
Systems biology analysis of pre-mRNA splicing and alternative splicing, and its role in cancers Monday September 7, 2009 at 13:00 CBS, DTU, Lyngby, Building 306, Auditorium 31
Pre-mRNA splicing reaction is a critical step of gene expression. Up to 95% of human gene sequences are intervening sequences (introns), and cells must
precisely excise the introns and ligate the coding sequences (exons) by splicing processes. More than three hundreds of proteins and many RNAs are involved in
this complex and elaborate processing, via a large number of RNA-RNA, proteinprotein, and RNA-protein interactions. Different exons and introns reorganization, called alternative splicing, can yield rearranged genes with altered functions, and it contributes to diversity of proteins based on the same
DNA sequences. The past years have witnessed the refinements in the understanding of network models of splicing/alternative splicing regulatory
elements and functions, but the detailed mechanism and evolution remain to be fully understood.
Different bioinformatics methods were described in this PhD thesis on splice site feature and pattern analyses; splice site prediction and alternative splicing
identification, from a variety of biological data, including ESTs, arrays and deepsequencing data.
The results on six projects/papers were collected, including the discovery of a surprising splicing strength pattern on genes, which is conserved in human and
mouse (Chapter II); the development of a well-performed web based splice site predictor by artificial neural networks (Chapter III); and the discovery of a
potential new class of very unusual intron splice sites, which could link to a "third spliceosome" or suggests a novel defense mechanism to avoid negative
regulation caused by microRNAs (Chapter IV). Those studies indicate a new vision to understand splicing mechanism, splicing fidelity, the relationship
between RNA processing and surveillance mechanism.
Alternative splicing generates diverse protein isoforms to function at different tissues or developmental stages; mutations can trigger aberrant splicing that can
cause human disease. From custom arrays and exon arrays, cell cycle-specific and cancer specific alternative splicing genes were identified (Chapter V and VI).
Currently the development of next generation deep-sequencing technology offers an opportunity and a desire to explore the new and huge biological data. A
number of novel alternative splicing sites were detected by deep sequencing from a brain tumor example (Chapter VII).
Everybody is welcome. Registration is not necessary. |