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dc.contributor.authorChrysostomou, Charalambos
dc.date.accessioned2014-04-17T08:35:03Z
dc.date.available2014-04-17T08:35:03Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/2086/9895
dc.descriptionDue to copyright reasons, the authors published papers have been removed from this copy of the thesis.en
dc.description.abstractProtein sequencing has produced overwhelming amount of protein sequences, especially in the last decade. Nevertheless, the majority of the proteins' functional and structural classes are still unknown, and experimental methods currently used to determine these properties are very expensive, laborious and time consuming. Therefore, automated computational methods are urgently required to accurately and reliably predict functional and structural classes of the proteins. Several bioinformatics methods have been developed to determine such properties of the proteins directly from their sequence information. Such methods that involve signal processing methods have recently become popular in the bioinformatics area and been investigated for the analysis of DNA and protein sequences and shown to be useful and generally help better characterise the sequences. However, there are various technical issues that need to be addressed in order to overcome problems associated with the signal processing methods for the analysis of the proteins sequences. Amino acid indices that are used to transform the protein sequences into signals have various applications and can represent diverse features of the protein sequences and amino acids. As the majority of indices have similar features, this project proposes a new set of computationally derived indices that better represent the original group of indices. A study is also carried out that resulted in finding a unique and universal set of best discriminating amino acid indices for the characterisation of allergenic proteins. This analysis extracts features directly from the protein sequences by using Discrete Fourier Transform (DFT) to build a classification model based on Support Vector Machines (SVM) for the allergenic proteins. The proposed predictive model yields a higher and more reliable accuracy than those of the existing methods. A new method is proposed for performing a multiple sequence alignment. For this method, DFT-based method is used to construct a new distance matrix in combination with multiple amino acid indices that were used to encode protein sequences into numerical sequences. Additionally, a new type of substitution matrix is proposed where the physicochemical similarities between any given amino acids is calculated. These similarities were calculated based on the 25 amino acids indices selected, where each one represents a unique biological protein feature. The proposed multiple sequence alignment method yields a better and more reliable alignment than the existing methods. In order to evaluate complex information that is generated as a result of DFT, Complex Informational Spectrum Analysis (CISA) is developed and presented. As the results show, when protein classes present similarities or differences according to the Common Frequency Peak (CFP) in specific amino acid indices, then it is probable that these classes are related to the protein feature that the specific amino acid represents. By using only the absolute spectrum in the analysis of protein sequences using the informational spectrum analysis is proven to be insufficient, as biologically related features can appear individually either in the real or the imaginary spectrum. This is successfully demonstrated over the analysis of influenza neuraminidase protein sequences. Upon identification of a new protein, it is important to single out amino acid responsible for the structural and functional classification of the protein, as well as the amino acids contributing to the protein's specific biological characterisation. In this work, a novel approach is presented to identify and quantify the relationship between individual amino acids and the protein. This is successfully demonstrated over the analysis of influenza neuraminidase protein sequences. Characterisation and identification problem of the Influenza A virus protein sequences is tackled through a Subgroup Discovery (SD) algorithm, which can provide ancillary knowledge to the experts. The main objective of the case study was to derive interpretable knowledge for the influenza A virus problem and to consequently better describe the relationships between subtypes of this virus. Finally, by using DFT-based sequence-driven features a Support Vector Machine (SVM)-based classification model was built and tested, that yields higher predictive accuracy than that of SD. The methods developed and presented in this study yield promising results and can be easily applied to proteomic fields.en
dc.language.isoenen
dc.publisherDe Montfort Universityen
dc.subjectamino acid indicesen
dc.subjectAllergensen
dc.subjectClassificationen
dc.subjectCluster of Differentiation 4en
dc.subjectDendrogramen
dc.subjectDiscrete Fourier Transformen
dc.subjectHierarchical Clusteringen
dc.subjectInfluenza A virusen
dc.subjectMultiple Sequence Alignmentsen
dc.subjectNeuraminidaseen
dc.subjectPrincipal Component Analysisen
dc.subjectProtein Sequencesen
dc.subjectSignal Processing Techniquesen
dc.subjectSubgroup Discoveryen
dc.subjectSupport Vector Machinesen
dc.titleCharacterisation and Classification of Protein Sequences by Using Enhanced Amino Acid Indices and Signal Processing-Based Methodsen
dc.typeThesis or dissertationen
dc.publisher.departmentFaculty of Technologyen
dc.publisher.departmentCentre for Computational Intelligenceen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhDen


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