ABSTRACT
Exceptionally accurate genome reference sequences have proven to be of great value to microbial researchers. Thus, to date, about 1800 bacterial genome assemblies have been "finished" at great expense with the aid of manual laboratory and computational processes that typically iterate over a period of months or even years. By applying a new laboratory design and new assembly algorithm to 16 samples, we demonstrate that assemblies exceeding finished quality can be obtained from whole-genome shotgun data and automated computation. Cost and time requirements are thus dramatically reduced.
Subject(s)
Bacteria/genetics , Genome, Bacterial , Genomic Library , Sequence Analysis, DNA/methods , AlgorithmsABSTRACT
Massively parallel DNA sequencing technologies are revolutionizing genomics by making it possible to generate billions of relatively short (~100-base) sequence reads at very low cost. Whereas such data can be readily used for a wide range of biomedical applications, it has proven difficult to use them to generate high-quality de novo genome assemblies of large, repeat-rich vertebrate genomes. To date, the genome assemblies generated from such data have fallen far short of those obtained with the older (but much more expensive) capillary-based sequencing approach. Here, we report the development of an algorithm for genome assembly, ALLPATHS-LG, and its application to massively parallel DNA sequence data from the human and mouse genomes, generated on the Illumina platform. The resulting draft genome assemblies have good accuracy, short-range contiguity, long-range connectivity, and coverage of the genome. In particular, the base accuracy is high (≥99.95%) and the scaffold sizes (N50 size = 11.5 Mb for human and 7.2 Mb for mouse) approach those obtained with capillary-based sequencing. The combination of improved sequencing technology and improved computational methods should now make it possible to increase dramatically the de novo sequencing of large genomes. The ALLPATHS-LG program is available at http://www.broadinstitute.org/science/programs/genome-biology/crd.
Subject(s)
Algorithms , Genomics/methods , Sequence Analysis, DNA/methods , Software , Animals , Genome/genetics , Humans , Internet , Mice , Reproducibility of ResultsABSTRACT
Quantum transport properties of porphyrin-bridged p-n junctions with Si leads are investigated by ab initio calculations. It is shown that this system exhibits strong negative differential resistance (NDR) peaks, whose magnitude and position can be controlled by the doping levels of the leads and by changing the central transition metal atom of the porphyrin. These results are explained by bias-induced on-off switching of resonant tunneling channels associated with specific molecular orbitals. The predicted behavior is general and should be observable for other organic molecules bridging doped semiconducting leads.
