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Analyzing Structural Rearrangements in Cancer Genomes
October 24, 2007 (03:30PM PDT - 04:15PM PDT)
The genomes of many cancers exhibit extensive chromosomal rearrangements including translocations, inversions, duplications and deletions. I will introduce computational methods for studying these rearrangements using data from paired-end sequencing of cancer genomes. In the paired-end approach, short “tag” sequences are obtained from fragments of cancer DNA, and these tags are aligned to the reference human genome sequence identifying locations of rearrangements. I will discuss two topics in the analysis of this data. First is the question of determining the amount of sequencing required to detect rearrangement breakpoints and to localize them precisely. I will show how extensions of the Lander-Waterman statistics address this question. Second, I will examine the possibility of deriving a parsimonious sequence of rearrangements that transform the normal human genome into a cancer genome. For this problem, I will introduce the Hannenhalli-Pevzner theory, which yields a sequence of inversions and translocations that produce one genome from another, and describe how duplications in cancer genomes can also be analyzed.
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