Thesis advisor: Gabor T. MarthDuring the last few years, numerous new sequencing technologies have emerged that require tools that can process large amounts of read data quickly and accurately. Regardless of the downstream methods used, reference-guided aligners are at the heart of all next-generation analysis studies. I have developed a general reference-guided aligner, MOSAIK, to support all current sequencing technologies (Roche 454, Illumina, Applied Biosystems SOLiD, Helicos, and Sanger capillary). The calibrated alignment qualities calculated by MOSAIK allow the user to fine-tune the alignment accuracy for a given study. MOSAIK is a highly configurable and easy-to-use suite of alignment tools that is used in hundreds of labs worldwide. MOSAIK is an integral part of our genetic variant discovery pipeline. From SNP and short-INDEL discovery to structural variation discovery, alignment accuracy is an essential requirement and enables our downstream analyses to provide accurate calls. In this thesis, I present three major studies that were formative during the development of MOSAIK and our analysis pipeline. In addition, I present a novel algorithm that identifies mobile element insertions (non-LTR retrotransposons) in the human genome using split-read alignments in MOSAIK. This algorithm has a low false discovery rate (4.4 %) and enabled our group to be the first to determine the number of mobile elements that differentially occur between any two individuals.Thesis (PhD) — Boston College, 2010.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Biology
