Here’s a good reference manual for using R and Bioconductor to work with high throughput sequencing data. The slides are also a good introduction to the sequencing methods.
High throughput sequencing (HT-Seq or HTS), also known as next generation sequencing (NGS), presents a wide spectrum of opportunities for genome research. Unfortunately, many existing bioinformatic tools do not scale well to large datasets consisting of tens of millions of sequences generated by technologies like Illumina/Solexa, Roche/454, ABI/SOLiD and Helicos. The Bioconductor project fills this gap by providing a rapidly growing suite of well designed R packages for analyzing traditional and HT-Seq datasets.