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Systematic Profiling of Alternative mRNA Splicing Signature for Predicting Glioblastoma Prognosis.

Xueran Chen | Chenggang Zhao | Bing Guo | Zhiyang Zhao | Hongzhi Wang | Zhiyou Fang
Frontiers in oncology | 2019

Emerging evidence suggests that alternative splicing (AS) is modified in cancer and is associated with cancer progression. Systematic analysis of AS signature in glioblastoma (GBM) is lacking and is greatly needed. We profiled genome-wide AS events in 498 GBM patients in TCGA using RNA-seq data, and splicing network and prognostic predictor were built by integrated bioinformatics analysis. Among 45,610 AS events in 10,434 genes, we detected 1,829 AS events in 1,311 genes, and 1,667 AS events in 1,146 genes that were significantly associated with overall survival and disease-free survival of GBM patients, respectively. Five potential feature genes, S100A4, ECE2, CAST, ASPH, and LY6K, were discovered after network mining as well as correlation analysis between AS and gene expression, most of which were related to carcinogenesis and development. Multivariate survival model analysis indicated that these five feature genes could classify the prognosis at AS event and gene expression level. This report opens up a new avenue for exploration of the pathogenesis of GBM through AS, thus more precisely guiding clinical treatment and prognosis judgment.

Pubmed ID: 31608231

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This is a list of tools and resources that we have found mentioned in this publication.


DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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Cytoscape (tool)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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SpliceSeq (tool)

RRID:SCR_005267

A Java application to investigate alternative mRNA splicing patterns in data from high-throughput mRNA sequencing studies. Sequence reads are mapped to splice graphs that unambiguously quantify the inclusion level of each exon and splice junction. The graphs are then traversed to predict the protein isoforms that are likely to result from the observed exon and splice junction reads. UniProt annotations are mapped to each protein isoform to identify potential functional impacts of alternative splicing. This tool may be used on a single RNASeq sample to identify genes with multiple spliceforms, on a pair of samples to identify differential splicing between the two, or on groups of samples to identify statistically significant group level differences in splicing patterns. SpliceSeq can be run from the install page as a java web start application to explore the sequencing data on their server or can be installed locally to analyze your own mRNA-Seq data.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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