GENOME-WIDE IDENTIFICATION OF DIFFERENTIAL SPLICING BASED ON RNA-SEQ DATA: FROM TOOL DEVELOPMENT TO RESEARCH APPLICATIONS

Abstract

A new genome-wide computational pipeline named SpliceScan was developed in this thesis to identify all differential splicing events based on the RNA-Seq data. SpliceScan was used to identify differential splicing events in myelodyspastic syndrome (MDS) patients with ZRSR2 mutation and in ZRSR2 knockdown TF-1 leukemia cell lines. We identified more than 90% of these differential splicing events are related to U12-type introns. These findings demonstrated that ZRSR2 regulated alternative splicing in hematological diseases and played an indispensable role in splicing of U12-type intron. SpliceScan also successfully predicted the differential splicing events in MCF7 breast cancer samples under normoxia, acute hypoxia and chronic hypoxia conditions. In comparison to normoxia, both the acute and chronic hypoxia conditions lead to an increase in the number of differential splicing candidates. An exonic splicing enhancer with a motif region “GGWC” is discovered during the exon skipping analysis in chronic hypoxia.