High-throughput DNA sequencing has considerably changed the possibilities for conducting biomedical research by measuring billions of short DNA or RNA fragments. A central computational problem, and for many applications a first step, consists of determining where the fragments came from in the original genome. In this article, we review the main techniques for generating the fragments, the main applications, and the main algorithmic ideas for computing a solution to the read alignment problem. In addition, we describe pitfalls and difficulties connected to determining the correct positions of reads.
