Searching, clustering and evaluating biological sequences

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2012

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Abstract

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 exponential, and so far,

has outpaced the rate of improvement of computer speed and capacity.

This rate of growth, however, makes analysis of new datasets

increasingly difficult, and highlights the need for efficient,

scalable and modular software tools.

Fortunately most types of analysis of sequence data involve a few

fundamental operations. Here we study three such problems, namely

searching for local alignments between two sets of sequences,

clustering sequences, and evaluating the assemblies made from sequence

fragments. We present simple and efficient heuristic algorithms for

these problems, as well as open source software tools which implement

these algorithms.

First, we present approximate seeds; a new type of seed for local

alignment search. Approximate seeds are a generalization of exact

seeds and spaced seeds, in that they allow for insertions and

deletions within the seed. We prove that approximate seeds are

completely sensitive. We also show how to efficiently find approximate

seeds using a suffix array index of the sequences.

Next, we present DNACLUST; a tool for clustering millions of DNA

sequence fragments. Although DNACLUST has been primarily made for

clustering 16S ribosomal RNA sequences, it can be used for other

tasks, such as removing duplicate or near duplicate sequences from a

dataset.

Finally, we present a framework for comparing (two or more) assemblies

built from the same set of reads. Our evaluation requires the set of

reads and the assemblies only, and does not require the true genome

sequence. Therefore our method can be used in de novo assembly

projects, where the true genome is not known. Our score is based on

probability theory, and the true genome is expected to obtain the

maximum score.

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