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Protein homology detection with sparse models
Descriptive
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Title
Protein homology detection with sparse models
Name
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Huang
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Pai-Hsi
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Pai-Hsi Huang
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author
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Pavlovic
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Vladimir
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Advisory Committee
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Vladimir Pavlovic
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chair
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Kulikowski
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Casimir
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Advisory Committee
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Casimir Kulikowski
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internal member
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Metaxas
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Dimitris
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Advisory Committee
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Dimitris Metaxas
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internal member
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Shokoufandeh
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Ali
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Advisory Committee
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Ali Shokoufandeh
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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theses
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2008
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2008-10
Language
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English
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electronic
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application/pdf
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xvii, 110 pages
Abstract
Establishing structural or functional relationship between sequences, for instance to infer the structural class of an unannotated protein, is a
key task in biological analysis. Protein sequences undergo complex transformations such as mutation, insertion and deletion during the evolutionary process and typically share low sequence similarity on the superfamily level, making the task for remote homology detection based on primary sequence only very challenging.
Based on previous studies stating that knowledge based on only a subset of critical positions and the preferred symbols on such positions are sufficient for remote homology detection, we present a series of works, each enforcing different notion of sparsity, to recover such critical positions. We first start with a generative model and present the sparse profile hidden Markov models. Such generative approach recovers some critical patterns and motivates the need for discriminative learning. In our second study, we present a discriminative approach to recover such critical positions and the preferred symbols. In our third study, we address the issue of very few positive training examples, accompanied by a large number of negative training examples, which is typical in many remote homology detection task. Such issue motivates the need for semi-supervised learning. However, though containing abundant useful and critical information, large uncurated sequence databases also contain a lot of noise, which may compromise the quality of the classifiers. As a result, we present a systematic and biologically motivated framework for semi-supervised learning with large uncurated sequence databases. Combined with a very fast string kernel, our method not only realizes rapid and accurate remote homology detection and show state-of-the-art performance, but also recovers some critical patterns conserved in superfamilies.
key task in biological analysis. Protein sequences undergo complex transformations such as mutation, insertion and deletion during the evolutionary process and typically share low sequence similarity on the superfamily level, making the task for remote homology detection based on primary sequence only very challenging.
Based on previous studies stating that knowledge based on only a subset of critical positions and the preferred symbols on such positions are sufficient for remote homology detection, we present a series of works, each enforcing different notion of sparsity, to recover such critical positions. We first start with a generative model and present the sparse profile hidden Markov models. Such generative approach recovers some critical patterns and motivates the need for discriminative learning. In our second study, we present a discriminative approach to recover such critical positions and the preferred symbols. In our third study, we address the issue of very few positive training examples, accompanied by a large number of negative training examples, which is typical in many remote homology detection task. Such issue motivates the need for semi-supervised learning. However, though containing abundant useful and critical information, large uncurated sequence databases also contain a lot of noise, which may compromise the quality of the classifiers. As a result, we present a systematic and biologically motivated framework for semi-supervised learning with large uncurated sequence databases. Combined with a very fast string kernel, our method not only realizes rapid and accurate remote homology detection and show state-of-the-art performance, but also recovers some critical patterns conserved in superfamilies.
Note
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Ph.D.
Note
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Includes bibliographical references (p. 103-108).
Subject
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Topic
Computer Science
Subject
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Topic
Proteins--Analysis--Mathematical models
Subject
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(authority = ETD-LCSH)
Topic
Homology theory
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17493
Identifier
ETD_1048
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NjNbRU
Identifier
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doi:10.7282/T35M6612
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ETD doctoral
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The author owns the copyright to this work.
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Copyright protected
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Open
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Pai-Hsi Huang
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Affiliation
Rutgers University. Graduate School - New Brunswick
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Non-exclusive ETD license
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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