Novel Computational Methods for Large Scale Genome Comparison

Conference Paper · January 2008with9 Reads
DOI: 10.1007/978-3-540-85861-4_9 · Source: DBLP
Conference: 2nd International Workshop on Practical Applications of Computational Biology and Bioinformatics, IWPACBB 2008, Salamanca, Spain, 22th-24th October 2008


    The current wealth of available genomic data provides an unprecedented opportunity to compare and contrast evolutionary histories
    of closely and distantly related organisms. The focus of this dissertation is on developing novel algorithms and software
    for efficient global and local comparison of multiple genomes and the application of these methods for a biologically relevant
    case study. The thesis research is organized into three successive phases, specifically: (1) multiple genome alignment of
    closely related species, (2) local multiple alignment of interspersed repeats, and finally, (3) a comparative genomics case
    study of Neisseria. In Phase 1, we first develop an efficient algorithm and data structure for maximal unique match search in multiple genome
    sequences. We implement these contributions in an interactive multiple genome comparison and alignment tool, M-GCAT, that
    can efficiently construct multiple genome comparison frameworks in closely related species. In Phase 2, we present a novel
    computational method for local multiple alignment of interspersed repeats. Our method for local alignment of interspersed
    repeats features a novel method for gapped extensions of chained seed matches, joining global multiple alignment with a homology
    test based on a hidden Markov model (HMM). In Phase 3, using the results from the previous two phases we perform a case study
    of neisserial genomes by tracking the propagation of repeat sequence elements in attempt to understand why the important pathogens
    of the neisserial group have sexual exchange of DNA by natural transformation. In conclusion, our global contributions in
    this dissertation have focused on comparing and contrasting evolutionary histories of related organisms via multiple alignment
    of genomes.