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        <identifier>oai:www.ideals.illinois.edu:2142/34549</identifier>
        <datestamp>2023-07-11</datestamp>
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        <thesis xmlns="http://www.ndltd.org/standards/metadata/etdms/1.1/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:dc="http://purl.org/dc/elements/1.1/" xsi:schemaLocation="http://www.ndltd.org/standards/metadata/etdms/1.1/ http://www.ndltd.org/standards/metadata/etdms/1.1/etdms11.xsd http://purl.org/dc/elements/1.1/ http://www.ndltd.org/standards/metadata/etdms/1.1/etdmsdc.xsd">
          <dc:contributor>Rodriguez-Zas, Sandra L.</dc:contributor>
          <dc:creator>Sadeque, Ahmed</dc:creator>
          <dc:date>2012-09-18T21:25:10Z</dc:date>
          <dc:date>2012-09-18T21:25:10Z</dc:date>
          <dc:date>2014-09-18T10:00:36Z</dc:date>
          <dc:date>2012-08</dc:date>
          <dc:date>2012-09-18T21:25:10Z</dc:date>
          <dc:date>2012-08</dc:date>
          <dc:description>Background
Alternative exon usage (AEU) is an important component of gene expression regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes such as cancer. Numerous studies have identified associations between gene expression and the brain cancer glioblastoma multiforme (GBM). The few consistent gene expression biomarkers of GBM that have been reported may be due to the limited consideration of AEU and the analytical approaches used. The objectives of this study were to develop a model that accounts for the
variations in expression present between the exons within a gene and to identify AEU biomarkers of GBM survival.
Methods
The expression of exons corresponding to 25,403 genes was related to the survival of 250
individuals diagnosed with GBM in a training data set. Genes exhibiting AEU in the training
data set were confirmed in an independent validation data set of 78 patients. A hierarchical
model allows the consideration of covariation between exons within a gene and of the effect of
the epidemiological characteristics of the patients was developed to identify associations
between exon expression and patient survival. The same model serves multi-exon models with
and without AEU and single-exon models.
Results
AEU associated with GBM survival was identified on 2477 genes (P-value &lt; 5.0E-04 (FDR adjusted P-value &lt; 5.0E-04). G-protein coupled receptor 98 (Gpr98) and epidermal growth factor (Egf) were among the genes exhibiting AEU with 30 and 9 exons associated with GBM survival, respectively. Pathways enriched among the AEU genes included focal adhesion, ECM-receptor interaction, ABC transporters and pathways in cancer. In addition, 24 multi-exon genes without AEU and 8 single-exon genes were associated with GBM survival (P-value &lt; 0.0005).
Conclusions
The inferred patterns of AEU were consistent with in silico AS models. The hierarchical model used offered a flexible and simple way to interpret and identify associations between survival that accommodates multi-exon genes with or without AEU and single exon genes.</dc:description>
          <dc:description>Item withdrawn by Rebecca Bryant (rabryant@illinois.edu) on 2012-07-10T18:43:08Z
Item was in collections:
University of Illinois Theses &amp; Dissertations (ID: 1)
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sadeque2_MS_UIUC_Thesis_Aug2012.pdf: 1146070 bytes, checksum: c5478775585b2a6e27b0e60653f1e4e4 (MD5)</dc:description>
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          <dc:description>Item marked as restricted to the 'Administrator' Group (id=1) by Seth Robbins (srobbins@illinois.edu) on 2012-09-18T21:27:27Z
Item is restricted until 2014-09-18T21:27:16Z</dc:description>
          <dc:description>Restriction data tranferred 2014-07-01T11:35:47-05:00
Original Data
Group with Access Administrator
Release Date: 2014-09-18 16:27:16 UTC
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system</dc:description>
          <dc:description>Limited Restriction Lifted for Item 34823 on 2014-09-18T10:00:36Z.</dc:description>
          <dc:identifier>http://hdl.handle.net/2142/34549</dc:identifier>
          <dc:language>en</dc:language>
          <dc:rights>Copyright 2012 Ahmed Sadeque</dc:rights>
          <dc:subject>Alternative Splicing (AS)</dc:subject>
          <dc:subject>Alternative Exon Usage (AEU)</dc:subject>
          <dc:subject>Glioblastoma (GBM)</dc:subject>
          <dc:title>Identification of alternative exon usage in cancer survival using hierarchical modeling</dc:title>
          <degree>
            <department>Animal Sciences</department>
            <departmentCode>1538</departmentCode>
            <discipline>Bioinformatics</discipline>
            <disciplineCode>4026</disciplineCode>
            <grantor>University of Illinois at Urbana-Champaign</grantor>
            <level>Thesis</level>
            <name>M.S.</name>
            <program>MS: Bioinformatics: AnSci-UIUC</program>
            <programCode>10KS5099MS</programCode>
          </degree>
        </thesis>
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