Looking at sequencing from one perspective, library preparation is straightforward. Sequencing a genome (whether bacterial on the order of 5 million bases or a human at 3 billion bases) is a shotgun-based affair with tens of millions to tens of billions of reads that overlap multiple times across the genome (known as ‘fold coverage’). (Thus a 30x human genome coverage would require some 90 billion bases, or a 15x coverage of each haploid allele.) Multiple random start points, 30-fold coverage across the entire genomic sample, one takes a gDNA sample, randomly shears it, attaches synthetic adapters, and off you go following the manufacturer’s protocol on getting sequence data out, whether by Roche / 454, Illumina GAIIx or HiSeq 2000, Life Technologies SOLiD or 5500xl, Pacific BioSciences RS, Illumina MiSeq, Life Technologies Ion Torrent PGM…