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Computational modeling and inference...

Wen, Ji.

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Computational modeling and inference of alternative splicing regulation.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Computational modeling and inference of alternative splicing regulation./
Author:	Wen, Ji.
Description:	164 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-09(E), Section: B.
Contained By:	Dissertation Abstracts International74-09B(E).
Subject:	Biology, Bioinformatics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3563682
ISBN:	9781303121708

Computational modeling and inference of alternative splicing regulation.
Wen, Ji.

Computational modeling and inference of alternative splicing regulation. - 164 p.

Source: Dissertation Abstracts International, Volume: 74-09(E), Section: B.

Thesis (Ph.D.)--University of Miami, 2013.

Alternative splicing of precursor mRNA (pre-mRNA) provides an important means of regulating gene expression and generating transcriptomic and proteomic diversity in most eukaryotes. A number of special proteins, named splicing factors, can regulate the alternative splicing process by binding to certain short subsequences on pre-mRNA, named splicing regulatory elements (SREs). Therefore, identification of these SREs and prediction of their combinatorial effects are very important to the understanding of the mechanisms that regulate splicing.

ISBN: 9781303121708Subjects--Topical Terms:

1018415
Biology, Bioinformatics.

Computational modeling and inference of alternative splicing regulation.
LDR:02953nam a2200325 4500 001 1963637
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008 150210s2013 ||||||||||||||||| ||eng d
020 $a 9781303121708
035 $a (MiAaPQ)AAI3563682
035 $a AAI3563682
040 $a MiAaPQ $c MiAaPQ
100 1 $a Wen, Ji. $3 2099933
245 1 0 $a Computational modeling and inference of alternative splicing regulation.
300 $a 164 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-09(E), Section: B.
500 $a Adviser: Xiaodong Cai.
502 $a Thesis (Ph.D.)--University of Miami, 2013.
520 $a Alternative splicing of precursor mRNA (pre-mRNA) provides an important means of regulating gene expression and generating transcriptomic and proteomic diversity in most eukaryotes. A number of special proteins, named splicing factors, can regulate the alternative splicing process by binding to certain short subsequences on pre-mRNA, named splicing regulatory elements (SREs). Therefore, identification of these SREs and prediction of their combinatorial effects are very important to the understanding of the mechanisms that regulate splicing.
520 $a In this dissertation, we develop two methods for identifying SREs and their interactions. In the first method, we use the traditional enrichment-based approach, which identifies SREs by comparing frequencies of all hexamers in two discriminative data sets generated from mouse RNA-Seq data. The SREs are identified as hexamers that are enriched in the positive data set but under-represented in the negative data set. We also analyze the position preference of the identified SREs and compare their frequencies in constitutive exons and alternatively spliced exons.
520 $a In the second method, we first derive a mathematical model for splicing regulation based on the principles of thermodynamics. We include the effects of both SREs and interactions between two SREs in the model. We then apply the model to identify SREs and SRE interactions with linear regression. Since the linear regression model contains a very large number of variables, the traditional inference method does not perform well. To overcome this problem, we develop a novel framework for inferring the high-dimensional linear model.
520 $a Finally, we systematically study the alternative regions, arising from alternative splicing, alternative first exon or alternative last exon events in 105 breast cancer patients using RNA-Seq data. The identified aberrant alternative regions show very interesting associations with cancer development and provide important candidates for cancer diagnosis and cancer therapies.
590 $a School code: 0125.
650 4 $a Biology, Bioinformatics. $3 1018415
650 4 $a Computer Science. $3 626642
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0715
690 $a 0984
690 $a 0487
710 2 $a University of Miami. $b Electrical and Computer Engineering (Engineering). $3 2092125
773 0 $t Dissertation Abstracts International $g 74-09B(E).
790 $a 0125
791 $a Ph.D.
792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3563682