7 research outputs found
Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology
BACKGROUND: Structural variants (SVs) are less common than single nucleotide polymorphisms and indels in the population, but collectively account for a significant fraction of genetic polymorphism and diseases. Base pair differences arising from SVs are on a much higher order (>100 fold) than point mutations; however, none of the current detection methods are comprehensive, and currently available methodologies are incapable of providing sufficient resolution and unambiguous information across complex regions in the human genome. To address these challenges, we applied a high-throughput, cost-effective genome mapping technology to comprehensively discover genome-wide SVs and characterize complex regions of the YH genome using long single molecules (>150Â kb) in a global fashion. RESULTS: Utilizing nanochannel-based genome mapping technology, we obtained 708 insertions/deletions and 17 inversions larger than 1Â kb. Excluding the 59 SVs (54 insertions/deletions, 5 inversions) that overlap with N-base gaps in the reference assembly hg19, 666 non-gap SVs remained, and 396 of them (60%) were verified by paired-end data from whole-genome sequencing-based re-sequencing or de novo assembly sequence from fosmid data. Of the remaining 270 SVs, 260 are insertions and 213 overlap known SVs in the Database of Genomic Variants. Overall, 609 out of 666 (90%) variants were supported by experimental orthogonal methods or historical evidence in public databases. At the same time, genome mapping also provides valuable information for complex regions with haplotypes in a straightforward fashion. In addition, with long single-molecule labeling patterns, exogenous viral sequences were mapped on a whole-genome scale, and sample heterogeneity was analyzed at a new level. CONCLUSION: Our study highlights genome mapping technology as a comprehensive and cost-effective method for detecting structural variation and studying complex regions in the human genome, as well as deciphering viral integration into the host genome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2047-217X-3-34) contains supplementary material, which is available to authorized users
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Hardware Accelerated Alignment Algorithm for Optical Labeled Genomes
De novo assembly is a widely used methodology in bioinformatics. However, the conventional short-read-based de novo assembly is incapable of reliably reconstructing the large-scale structures of human genomes. Recently, a novel optical label-based technology has enabled reliable large-scale de novo assembly. Despite its advantage in large-scale genome analysis, this new technology requires a more computationally intensive alignment algorithm than its conventional counterpart. For example, the runtime of reconstructing a human genome is on the order of 10,000 hours on a sequential CPU. Therefore, in order to practically apply this new technology in genome research, accelerated approaches are desirable. In this article, we present three different accelerated approaches, multicore CPU, GPU, and FPGA. Against the sequential software baseline, our multicore CPU design achieved an 8.4× speedup, while the GPU and FPGA designs achieved 13.6× and 115× speedups, respectively. We also discuss the details of the design space exploration of this new assembly algorithm on these three different devices. Finally, we compare these devices in performance, optimization techniques, prices, and design efforts
Submicron Streptavidin Patterns for Protein Assembly
Micron and submicron-scale features of aldehyde functionality were fabricated in polymer films by photolithography to develop a platform for protein immobilization and assembly at a biologically relevant scale. Films containing the pH-reactive polymer poly(3,3‘-diethoxypropyl methacrylate) and a photoacid generator (PAG) were patterned from 500 nm to 40 μm by exposure to 365 nm (i-line) light. Upon PAG activation and hydrolysis of acetals, aldehyde groups formed. After the films were incubated with a biotinylated aldehyde reactive probe, the X-ray photoelectron spectroscopy results were consistent with biotin being attached to the surface. The background was subsequently passivated by flood exposure and incubation with an aminooxy-terminated poly(ethylene glycol), resulting in a 98% reduction in nonspecific protein adsorption. Protein patterning and assembly was demonstrated using streptavidin, biotinylated anthrax toxin receptor-1, and the protective antigen moiety of anthrax toxin and confirmed by fluorescence microscopy and atomic force microscopy (AFM). AFM demonstrated that 500 nm protein features were achieved. Because of the abundance of biotinylated proteins, this methodology provides a platform for protein immobilization and assembly for various applications in biotechnology