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  • 1
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    RiboFR-Seq: a novel approach to linking 16S rRNA amplicon profiles to metagenomes (2016)
    Oxford University Press
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    Publication Date: 2016-06-03
    Description: 16S rRNA amplicon analysis and shotgun metagenome sequencing are two main culture-independent strategies to explore the genetic landscape of various microbial communities. Recently, numerous studies have employed these two approaches together, but downstream data analyses were performed separately, which always generated incongruent or conflict signals on both taxonomic and functional classifications. Here we propose a novel approach, RiboFR-Seq (Ribosomal RNA gene flanking region sequencing), for capturing both ribosomal RNA variable regions and their flanking protein-coding genes simultaneously. Through extensive testing on clonal bacterial strain, salivary microbiome and bacterial epibionts of marine kelp, we demonstrated that RiboFR-Seq could detect the vast majority of bacteria not only in well-studied microbiomes but also in novel communities with limited reference genomes. Combined with classical amplicon sequencing and shotgun metagenome sequencing, RiboFR-Seq can link the annotations of 16S rRNA and metagenomic contigs to make a consensus classification. By recognizing almost all 16S rRNA copies, the RiboFR-seq approach can effectively reduce the taxonomic abundance bias resulted from 16S rRNA copy number variation. We believe that RiboFR-Seq, which provides an integrated view of 16S rRNA profiles and metagenomes, will help us better understand diverse microbial communities.
    Keywords: Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation (2016)
    Oxford University Press
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    Publication Date: 2016-01-29
    Description: Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G〉T, p.191Gly〉Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G〉A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G〉A mutation, or both m.11778G〉A and heterozygous p.191Gly〉Val mutations and symptomatic subjects harboring m.11778G〉A and homozygous p.191Gly〉Val mutations) and controls lacking these mutations. The 191Gly〉Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA Tyr were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly〉Val and m.11778G〉A mutations. The failure in tRNA Tyr metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly〉Val and m.11778G〉A mutations. The YARS2 p.191Gly〉Val mutation worsened the respiratory phenotypes associated with m.11778G〉A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G〉A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2 .
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Secure-TWS: Authenticating Node to Multi-user Communication in Shared Sensor Networks (2012)
    Oxford University Press
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    Publication Date: 2012-03-28
    Description: Recent works have shown the usefulness of network and application layer protocols that connect low-power sensor nodes directly to multiple applications and users on the Internet. We propose a security solution for this scenario. While previous works have provided security support for various communication patterns in sensor networks, such as among nodes, from nodes to a base station, and from users to nodes, the security of communication from sensor nodes to multiple users has not been sufficiently addressed. Specifically, we explore this design space and develop a security solution, named Secure Tiny Web Service, for efficient authentication of data sent by a resource-constrained sensor node to multiple users, using digital signatures. We investigate the resource overheads in communication and computation of four suitable signature schemes—the Elliptic Curve Digital Signature Algorithm, the (elliptic curve) Schnorr signature, and the Boneh–Lynn–Shacham and Zhang–Safavi-Naini–Susilo short signature schemes. We implement these schemes on two popular sensor node architectures (based on AVR ATmega128L and MSP430 processors with 802.15.4 radios) and experimentally characterize relevant trade-offs.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
    Published by Oxford University Press
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  • 4
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    An Orthogonal Genetic Algorithm for QoS-Aware Service Composition (2016)
    Oxford University Press
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    Publication Date: 2016-12-10
    Description: Service composition has been proven to be a convincing computing paradigm for rapidly constructing large-scale distributed applications within and across organizational boundaries. Quality of service (QoS)-aware service composition, i.e. selection of the optimal execution plan that maximizes the composition's end-to-end QoS properties, is an active area of research and development endeavors in service composition. In this article, we propose an orthogonal genetic algorithm (OGA) for QoS-aware service composition problem. Its significant feature is to incorporate an orthogonal design method into the initial population generation process and crossover operation. As a result, our algorithm is more robust and can search the solution space in a statistically sound manner. We have executed the OGA to solve 81 randomly generated service composition problems with different sizes and structures based on QWS data set including 2507 real Web services. The results indicate that our OGA can find near-optimal solutions within moderate numbers of generation and has the performance superiority in comparison with many existing optimization algorithms.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
    Published by Oxford University Press
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  • 5
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    Ancestry of the Australian Termitivorous Numbat (2013)
    Oxford University Press
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    Publication Date: 2013-04-16
    Description: The Australian numbat, Myrmecobius fasciatus , is the only marsupial that feeds almost exclusively on termites and that has a life following the diurnally restricted and dynamic geographical distribution of termites. The millions of years of this adaptation led to unique morphological and anatomical features, especially basicranial and dental characteristics, that make it difficult to identify a clear phylogenetic affiliation to other marsupials. From DNA sequence analyses, the family Myrmecobiidae is placed within the dasyuromorph marsupials, but the exact position varies from study to study, and support values are mostly rather modest. Here, we report the recovery and analysis of approximately 110,000 quasifossilized traces of mobile element insertions into the genome of a dasyurid marsupial (Tasmanian devil), 25 of which are phylogenetically informative for early dasyuromorphial evolution. Fourteen of these ancient retroposon insertions are shared by the 16 Dasyuromorphia species analyzed, including the numbat, but are absent in the outgroups. An additional 11 other insertions are present in all Dasyuridae but are absent in the numbat. These findings place numbats as the sister group to all living Dasyuridae and show that the investigated Dasyuromorphia, including the Myrmecobiidae, constitutes a monophyletic group that is separated from Peramelemorphia, Notoryctemorphia, and other marsupials.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    A genome-wide meta-analysis identifies two novel loci associated with high myopia in the Han Chinese population (2013)
    Oxford University Press
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    Publication Date: 2013-05-14
    Description: High myopia, highly prevalent in the Chinese population, is a leading cause of visual impairment worldwide. Genetic factors play a critical role in the development of this visual disorder. Genome-wide association studies in recent years have revealed several chromosomal regions that contribute to its progression. To identify additional genetic variants for high myopia susceptibility, we used a genome-wide meta-analysis to examine the associations between the disease and 286 031 single-nucleotide polymorphisms (SNPs) in a combined cohort of 665 cases and 960 controls. The most significant SNPs ( n = 61) were genotyped in a replication cohort (850 cases and 1197 controls), and 14 SNPs were further tested through genotyping in two additional validation cohorts (combined 1278 cases and 2486 controls). As a result of this analysis, four SNPs reached genome-wide significance ( P 〈 2.0 x 10 –7 ). The most significantly associated SNP, rs2730260 [overall P = 8.95 x 10 –14 ; odds ratio (95% CI) =1.33 (1.23–1.44)], is located in the VIPR2 gene, which is located in the MYP4 locus. The other three SNPs (rs7839488, rs4395927 and rs4455882) in the same linkage disequilibrium block are located in the SNTB1 gene, with ­P values ranging from 1.13 x 10 –8 to 2.13 x 10 –11 . The VIPR2 and SNTB1 genes are expressed in the retina and the retinal pigment epithelium and have been previously reported to have potential functions for the pathogenesis of myopia. Our results suggest that variants of the VIPR2 and SNTB1 genes increase susceptibility to high myopia in Han Chinese.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Protein threading using context-specific alignment potential (2013)
    Oxford University Press
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    Publication Date: 2013-06-24
    Description: Motivation: Template-based modeling, including homology modeling and protein threading, is the most reliable method for protein 3D structure prediction. However, alignment errors and template selection are still the main bottleneck for current template-base modeling methods, especially when proteins under consideration are distantly related. Results: We present a novel context-specific alignment potential for protein threading, including alignment and template selection. Our alignment potential measures the log-odds ratio of one alignment being generated from two related proteins to being generated from two unrelated proteins, by integrating both local and global context-specific information. The local alignment potential quantifies how well one sequence residue can be aligned to one template residue based on context-specific information of the residues. The global alignment potential quantifies how well two sequence residues can be placed into two template positions at a given distance, again based on context-specific information. By accounting for correlation among a variety of protein features and making use of context-specific information, our alignment potential is much more sensitive than the widely used context-independent or profile-based scoring function. Experimental results confirm that our method generates significantly better alignments and threading results than the best profile-based methods on several large benchmarks. Our method works particularly well for distantly related proteins or proteins with sparse sequence profiles because of the effective integration of context-specific, structure and global information. Availability: http://raptorx.uchicago.edu/download/ . Contact: jinboxu@gmail.com
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 8
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    BreakSeek: a breakpoint-based algorithm for full spectral range INDEL detection (2015)
    Oxford University Press
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    Publication Date: 2015-08-18
    Description: Although recent developed algorithms have integrated multiple signals to improve sensitivity for insertion and deletion (INDEL) detection, they are far from being perfect and still have great limitations in detecting a full size range of INDELs. Here we present BreakSeek, a novel breakpoint-based algorithm, which can unbiasedly and efficiently detect both homozygous and heterozygous INDELs, ranging from several base pairs to over thousands of base pairs, with accurate breakpoint and heterozygosity rate estimations. Comprehensive evaluations on both simulated and real datasets revealed that BreakSeek outperformed other existing methods on both sensitivity and specificity in detecting both small and large INDELs, and uncovered a significant amount of novel INDELs that were missed before. In addition, by incorporating sophisticated statistic models, we for the first time investigated and demonstrated the importance of handling false and conflicting signals for multi-signal integrated methods.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Secure-TWS: Authenticating Node to Multi-user Communication in Shared Sensor Networks (2011)
    Oxford University Press
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    Publication Date: 2011-09-08
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
    Published by Oxford University Press
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  • 10
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    PlasmoGF: an integrated system for comparative genomics and phylogenetic analysis of Plasmodium gene families (2008)
    Oxford University Press
    Details
    Publication Date: 2008-03-12
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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