Title of dissertation: SEARCHING, CLUSTERING AND EVALUATING BIOLOGICAL SEQUENCES Mohammadreza Ghodsi, Doctor of Philosophy, 2012 Dissertation directed by: Professor Mihai Pop Department of Computer Science The latest generation of biological sequencing technologies have made it possible to generate sequence data faster and cheaper than ever before. The growth of sequence data has been exponenti...

Dynamic programming [1] has full sensitivity, but too slow for large scale homology search. FASTA / BLAST type of heuristics [2] trade sensitivity for speed. Can we have both sensitivity and speed? We present the mathematical theory of optimized spaced seeds which allows modern homology search to achieve high sensitivity and high speed simultaneously. The spaced seed methodology is implemented ...

Whole-genome bisulfite sequencing (WGBS) has emerged as the gold-standard technique in genome-scale studies of DNA methylation. Mapping reads from WGBS requires unique considerations that make the process more time-consuming than in other sequencing applications. Typical WGBS data sets contain several hundred million reads, adding to this analysis challenge. We present the WALT tool for mapping...

Spaced seeds have been recently shown to not only detect more alignments, but also to give a more accurate measure of phylogenetic distances, and to provide a lower misclassification rate when used with Support Vector Machines (SVMs). We confirm by independent experiments these two results, and propose in this article to use a coverage criterion to measure the seed efficiency in both cases in o...

We propose a new method and its associated algorithm to e ciently compute seed sensitivity when considering that High Throughput Sequencing reads are mapped along sub-parts of a known HMM alignment profile. This computation particularly makes sense with positioned spaced seeds. It relies on both automata theory (previous work [KNR06]) combined with a matrix product problem. Interestingly, it br...

Single Molecule Sequencing technologies such as the Heliscope simplify the preparation of DNA for sequencing, while sampling millions of reads in a day. Simultaneously, the technology suffers from a significantly higher error rate, ameliorated by the ability to sample multiple reads from the same location. In this paper we develop novel rapid alignment algorithms for two-pass Single Molecule Se...