subject:(Exon usage)

University of Illinois – Urbana-Champaign

1. Sadeque, Ahmed. Identification of alternative exon usage in cancer survival using hierarchical modeling.

Degree: MS, 4026, 2012, University of Illinois – Urbana-Champaign

► 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… (more)

▼ 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 < 5.0E-04 (FDR adjusted P-value < 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 < 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. Advisors/Committee Members: Rodriguez-Zas, Sandra L. (advisor).

Subjects/Keywords: Alternative Splicing (AS); Alternative Exon Usage (AEU); Glioblastoma (GBM)

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sadeque, A. (2012). Identification of alternative exon usage in cancer survival using hierarchical modeling. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/34549

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sadeque, Ahmed. “Identification of alternative exon usage in cancer survival using hierarchical modeling.” 2012. Thesis, University of Illinois – Urbana-Champaign. Accessed February 27, 2021. http://hdl.handle.net/2142/34549.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sadeque, Ahmed. “Identification of alternative exon usage in cancer survival using hierarchical modeling.” 2012. Web. 27 Feb 2021.

Vancouver:

Sadeque A. Identification of alternative exon usage in cancer survival using hierarchical modeling. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2142/34549.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sadeque A. Identification of alternative exon usage in cancer survival using hierarchical modeling. [Thesis]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/34549

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

2. Ruddy, Sean. Shrinkage of dispersion parameters in the double exponential family of distributions, with applications to genomic sequencing.

Degree: Statistics, 2014, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/3rv7g03q

► The prevalence of sequencing experiments in genomics has led to an increased use of methods for count data in analyzing high-throughput genomic data to perform… (more)

▼ The prevalence of sequencing experiments in genomics has led to an increased use of methods for count data in analyzing high-throughput genomic data to perform analyses. The importance of shrinkage methods in improving the performance of statistical methods remains. A common example is that of gene expression data, where the counts per gene are often modeled as some form of an overdispersed Poisson. In this case, shrinkage estimates of the per-gene dispersion parameter have lead to improved estimation of dispersion in the case of a small number of samples. We address a different count setting introduced by the use of sequencing data: comparing differential proportional usage via an overdispersed binomial model. Such a model can be useful for testing differential exon inclusion in mRNA-Seq experiments in addition to the typical differential gene expression analysis. In this setting, there are fewer such shrinkage methods for the dispersion parameter. We introduce a novel method that is developed by modeling the dispersion based on the double exponential family of distributions proposed by Efron (1986), also known as the exponential dispersion model (Jorgensen, 1987). Our methods (WEB-Seq and DEB-Seq) are empirical bayes strategies for producing a shrunken estimate of dispersion that can be applied to any double exponential dispersion family, though we focus on the binomial and poisson. These methods effectively detect differential proportional usage, and have close ties to the weighted likelihood strategy of edgeR developed for gene expression data (Robinson and Smyth, 2007; Robinson et al., 2010). We analyze their behavior on simulated data sets as well as real data for both differential exon usage and differential gene expression. In the exon usage case, we will demonstrate our methods' superior ability to control the FDR and detect truly different features compared to existing methods. In the gene expression setting, our methods fail to control the FDR; however, the rankings of the genes by p-value is among the top performers and proves to be robust to both changes in the probability distribution used to generate the counts and in low sample size situations. We provide implementation of our methods in the R package DoubleExpSeq available from the Comprehensive R Archive Network (CRAN).

Subjects/Keywords: Statistics; Genetics; Biology; Differential Expression; Empirical Bayes; Exon Usage; Overdispersion; RNA-Seq; Shrinkage

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ruddy, S. (2014). Shrinkage of dispersion parameters in the double exponential family of distributions, with applications to genomic sequencing. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/3rv7g03q

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ruddy, Sean. “Shrinkage of dispersion parameters in the double exponential family of distributions, with applications to genomic sequencing.” 2014. Thesis, University of California – Berkeley. Accessed February 27, 2021. http://www.escholarship.org/uc/item/3rv7g03q.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ruddy, Sean. “Shrinkage of dispersion parameters in the double exponential family of distributions, with applications to genomic sequencing.” 2014. Web. 27 Feb 2021.

Vancouver:

Ruddy S. Shrinkage of dispersion parameters in the double exponential family of distributions, with applications to genomic sequencing. [Internet] [Thesis]. University of California – Berkeley; 2014. [cited 2021 Feb 27]. Available from: http://www.escholarship.org/uc/item/3rv7g03q.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ruddy S. Shrinkage of dispersion parameters in the double exponential family of distributions, with applications to genomic sequencing. [Thesis]. University of California – Berkeley; 2014. Available from: http://www.escholarship.org/uc/item/3rv7g03q

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas – Austin

3. Wolfe, Sarah Anne. Molecular mechanisms underlying alcohol use disorder and major depressive disorder comorbidity.

Degree: PhD, Cellular and Molecular Biology, 2017, University of Texas – Austin

URL: http://dx.doi.org/10.26153/tsw/2231

► Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD) are two widespread and debilitating disorders that share a high rate of comorbidity with the presence… (more)

▼ Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD) are two widespread and debilitating disorders that share a high rate of comorbidity with the presence of either disorder doubling the risk of developing the other. Despite their prevalence, few treatments are available to individuals with comorbid AUD and MDD. Both alcohol and antidepressants promote lasting neuroadaptive changes in synapses and dendrites. With alcohol these changes may provide relief from depressive symptoms, and the initial use of alcohol may be a form of self-medication for individuals with MDD, suggesting ethanol may have antidepressant properties underlying similarities in neurobiological abnormalities. However, the synaptic pathways that are shared by alcohol and antidepressants are unknown. This study aims to identify why acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviors. To understand the functional basis of these behaviors, a molecular pathway activated by rapid antidepressants was investigated. Here ethanol, like rapid antidepressants, altered γ-aminobutyric acid type B receptor (GABA [subscript B] R) expression and signaling, to increase dendritic calcium. New GABA [subscript B] Rs were synthesized in response to ethanol treatment, requiring fragile-X mental retardation protein (FMRP). Ethanol-dependent changes in GABA [subscript B] R expression, dendritic signaling, and antidepressant efficacy were absent in Fmr1-knockout (KO) mice. These findings indicate that FMRP is an important regulator of protein synthesis following acute alcohol exposure, and provided a molecular basis for the antidepressant efficacy of acute ethanol exposure. We identify alterations on a global scale with acute alcohol and antidepressant by sequencing the synaptic transcriptome. We identified parallel alterations in exon usage with acute alcohol and antidepressant treatment. These shared differentially expressed exons may give rise to isoforms and proteins with altered function or localization in the synapse. Some of these differentially expressed exons were identified in genes known to have alternative isoforms with AUD and MDD. These data implicate alternative splicing and isoform expression in the acute antidepressant-like effects of ethanol and the development of comorbid alcohol and depression. Understanding the molecular basis for comorbidity may aid in development of treatment options for afflicted individuals with dual disorders, as well as explore the mechanism for the initiation of addiction with acute exposure to alcohol Advisors/Committee Members: Harris, R. Adron (advisor), Raab-Graham, Kimberly F. (advisor), Golding, Nace (committee member), Morrisett, Richard (committee member), Macdonald, Paul (committee member).

Subjects/Keywords: Alcohol use disorder; Major depressive disorder; Ethanol; Rapid antidepressants; FMRP; GABABR; Ro 25-6981; RNA-sequencing; Synaptoneurosomes; Exon usage

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wolfe, S. A. (2017). Molecular mechanisms underlying alcohol use disorder and major depressive disorder comorbidity. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://dx.doi.org/10.26153/tsw/2231

Chicago Manual of Style (16^th Edition):

Wolfe, Sarah Anne. “Molecular mechanisms underlying alcohol use disorder and major depressive disorder comorbidity.” 2017. Doctoral Dissertation, University of Texas – Austin. Accessed February 27, 2021. http://dx.doi.org/10.26153/tsw/2231.

MLA Handbook (7^th Edition):

Wolfe, Sarah Anne. “Molecular mechanisms underlying alcohol use disorder and major depressive disorder comorbidity.” 2017. Web. 27 Feb 2021.

Vancouver:

Wolfe SA. Molecular mechanisms underlying alcohol use disorder and major depressive disorder comorbidity. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2017. [cited 2021 Feb 27]. Available from: http://dx.doi.org/10.26153/tsw/2231.

Council of Science Editors:

Wolfe SA. Molecular mechanisms underlying alcohol use disorder and major depressive disorder comorbidity. [Doctoral Dissertation]. University of Texas – Austin; 2017. Available from: http://dx.doi.org/10.26153/tsw/2231

Brno University of Technology

4. Abo Khayal, Layal. Transkriptomická charakterizace pomocí analýzy RNA-Seq dat: Transcriptomic Characterization Using RNA-Seq Data Analysis.

Degree: 2019, Brno University of Technology

URL: http://hdl.handle.net/11012/70129

► The high-throughputs sequence technologies produce a massive amount of data, that can reveal new genes, identify splice variants, and quantify gene expression genome-wide. However, the… (more)

Subjects/Keywords: RNA-Seq; diferenciální genová exprese (DGE); alternativní splicing; diferenciální použití exonů (DEU); dlouhá nekódující RNA (lncRNA); RNA-Seq; Differential Gene Expression (DGE); Alternative splicing; Differential Exon Usage (DEU); long non-coding RNA (lncRNA).

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Abo Khayal, L. (2019). Transkriptomická charakterizace pomocí analýzy RNA-Seq dat: Transcriptomic Characterization Using RNA-Seq Data Analysis. (Thesis). Brno University of Technology. Retrieved from http://hdl.handle.net/11012/70129

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Abo Khayal, Layal. “Transkriptomická charakterizace pomocí analýzy RNA-Seq dat: Transcriptomic Characterization Using RNA-Seq Data Analysis.” 2019. Thesis, Brno University of Technology. Accessed February 27, 2021. http://hdl.handle.net/11012/70129.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Abo Khayal, Layal. “Transkriptomická charakterizace pomocí analýzy RNA-Seq dat: Transcriptomic Characterization Using RNA-Seq Data Analysis.” 2019. Web. 27 Feb 2021.

Vancouver:

Abo Khayal L. Transkriptomická charakterizace pomocí analýzy RNA-Seq dat: Transcriptomic Characterization Using RNA-Seq Data Analysis. [Internet] [Thesis]. Brno University of Technology; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11012/70129.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Abo Khayal L. Transkriptomická charakterizace pomocí analýzy RNA-Seq dat: Transcriptomic Characterization Using RNA-Seq Data Analysis. [Thesis]. Brno University of Technology; 2019. Available from: http://hdl.handle.net/11012/70129

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

		in
And / Or
		in
And / Or
		in
And / Or
		in

Open Access Theses and Dissertations