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A Self-Adaptive Spectral Rotation Approach to Detection of DNA Sequence Periodicities and Their Relationship with Molecular Mechanisms

Posted on:2012-12-10Degree:Ph.DType:Dissertation
University:Hong Kong Polytechnic University (Hong Kong)Candidate:Chen, BoFull Text:PDF
GTID:1460390011967969Subject:Computer Science
Abstract/Summary:
Computational investigations into the relationship and interaction between DNA sequences and cell components help biologists and medical scientists to address many important issues. This study initiates a new approach, namely, Self-Adaptive Spectral Rotation (SASR), to investigate the relationship between periodicities in DNA sequences and various molecular mechanisms in cells. This newly developed approach could be very useful in fields of bioinformatics, including protein-coding region prediction and nucleosome positioning prediction.;Protein-coding region prediction, especially computational methods to find locations of protein-coding regions in uncharacterized DNA sequences, is a meaningful issue in computational molecular biology. In this study, the SASR approach is first developed to visualize a coding related feature, i.e., the Triplet Periodicity (TP), in DNA sequences. Applications on real genomic datasets show that, in SASR's output, the graphic patterns for coding and non-coding regions differ so significantly that the former can be visually distinguished from the latter. Such visualization by the SASR approach requires no training process, and takes the advantage of "auto-scale analysis ability" from human vision, Besides, a T-Z-T approach is developed to extract numerical information from the SASR's graphic result. The combination of the SASR and the T-Z-T provides computational predictions of coding regions without any training process.;Experimental studies on nucleosome positioning have revealed the preference of nucleosome binding for certain regions of a DNA sequence. However, it is still not clear whether such a binding preference is sequence-specific. In this study, the original SASR approach is extended to investigate the relationship between nucleosome formation and the ∼10bp periodicity of dinucleotides in DNA sequences. A Genetic Algorithm (GA) based method is developed to identify which dinucleotide combination mostly connects its ∼10bp periodicity with nucleosome formation. The results from the GA support the "sequence-specific" argument of nucleosome formation, and also imply some new principles of nucleosome formation.;Besides the TP and the ∼10bp periodicity, in this study, another extension of the SASR approach, i.e., the mature SASR, shows its ability to detect a hypothetical anti-TP property in DNA sequences. Some real DNA fragments are found with such an anti-TP property by using the mature SASR.
Keywords/Search Tags:DNA, SASR, Approach, Relationship, Nucleosome formation, Molecular
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