Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2000. ; Includes bibliographical references (leaves 180-191). ; The field of genomics provides many challenges to computer scientists and mathematicians. The area of computational genomics has been expanding recently, and the timely application of computer science in this field is proving to be an essential component of the large international effort in genomics. In this thesis we address key issues in the different stages of genome research: planning of a genome sequencing project, obtaining and assembling sequence information, and ultimately study, cross-species comparison, and annotation of finished genomic sequence. We present applications of computational techniques to the above areas: (1) In relation to the early stages of a genome project, we address physical mapping, and we present results on the theoretical problem of finding minimum superstrings of hypergraphs, a combinatorial problem motivated by physical mapping. We also present a statistical and simulation study of "walking with clone-end sequences", an important method for sequencing a large genome. ; (cont.) (2) Turning to the problem of obtaining the finished genomic sequence, we present ARACHNE, a prototype software system for assembling sequence data that are derived from sequencing a genome with the "shotgun" method. (3) Finally, we turn to the computational analysis of finished genomic sequence. We present GLASS, a software system for obtaining global pairwise alignments of orthologous finished sequences. We finally use GLASS to perform a comparative structure and sequence analysis of orthologous human and mouse genomic regions, and develop ROSETTA, the first cross-species comparison-based system for the prediction of protein coding regions in genomic sequences. ; by Serafin Batzoglou. ; Ph.D.