Two recent papers using different approaches reported draft sequences of the human genome. The international Human Genome Project (HGP) used the hierarchical shotgun approach, whereas Celera Genomics adopted the whole-genome shotgun (WGS) approach. Here, we analyze whether the latter paper provides a meaningful test of the WGS approach on a mammalian genome. In the Celera paper, the authors did not analyze their own WGS data. Instead, they decomposed the HGP's assembled sequence into a "perfect tiling path", combined it with their WGS data, and assembled the merged data set. To study the implications of this approach, we perform computational analysis and find that a perfect tiling path with 2-fold coverage is sufficient to recover virtually the entirety of a genome assembly. We also examine the manner in which the assembly was anchored to the human genome and conclude that the process primarily depended on the HGP's sequence-tagged site maps, BAC maps, and clone-based sequences. Our analysis indicates that the Celera paper provides neither a meaningful test of the WGS approach nor an independent sequence of the human genome. Our analysis does not imply that a WGS approach could not be successfully applied to assemble a draft sequence of a large mammalian genome, but merely that the Celera paper does not provide such evidence.


Waterston RH, Lander ES, Sulston JE.

Institute Authors