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  • 1
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    Meta-analysis of genome-wide association data identifies novel susceptibility loci for obesity (2013)
    Oxford University Press
    Details
    Publication Date: 2013-09-23
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Indel and Carryforward Correction (ICC): a new analysis approach for processing 454 pyrosequencing data (2013)
    Oxford University Press
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    Publication Date: 2013-09-20
    Description: Motivation: Pyrosequencing technology provides an important new approach to more extensively characterize diverse sequence populations and detect low frequency variants. However, the promise of this technology has been difficult to realize, as careful correction of sequencing errors is crucial to distinguish rare variants (~1%) in an infected host with high sensitivity and specificity. Results: We developed a new approach, referred to as Indel and Carryforward Correction (ICC), to cluster sequences without substitutions and locally correct only indel and carryforward sequencing errors within clusters to ensure that no rare variants are lost. ICC performs sequence clustering in the order of (i) homopolymer indel patterns only, (ii) indel patterns only and (iii) carryforward errors only, without the requirement of a distance cutoff value. Overall, ICC removed 93–95% of sequencing errors found in control datasets. On pyrosequencing data from a PCR fragment derived from 15 HIV-1 plasmid clones mixed at various frequencies as low as 0.1%, ICC achieved the highest sensitivity and similar specificity compared with other commonly used error correction and variant calling algorithms. Availability and implementation: Source code is freely available for download at http://indra.mullins.microbiol.washington.edu/ICC . It is implemented in Perl and supported on Linux, Mac OS X and MS Windows. Contact: jmullins@uw.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 3
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    Incorporating prior knowledge into Gene Network Study (2013)
    Oxford University Press
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    Publication Date: 2013-10-04
    Description: Motivation: A major goal in genomic research is to identify genes that may jointly influence a biological response. From many years of intensive biomedical research, a large body of biological knowledge, or pathway information, has accumulated in available databases. There is a strong interest in leveraging these pathways to improve the statistical power and interpretability in studying gene networks associated with complex phenotypes. This prior information is a valuable complement to large-scale genomic data such as gene expression data generated from microarrays. However, it is a non-trivial task to effectively integrate available biological knowledge into gene expression data when reconstructing gene networks. Results: In this article, we developed and applied a Lasso method from a Bayesian perspective, a method we call prior Lasso (pLasso), for the reconstruction of gene networks. In this method, we partition edges between genes into two subsets: one subset of edges is present in known pathways, whereas the other has no prior information associated. Our method assigns different prior distributions to each subset according to a modified Bayesian information criterion that incorporates prior knowledge on both the network structure and the pathway information. Simulation studies have indicated that the method is more effective in recovering the underlying network than a traditional Lasso method that does not use the prior information. We applied pLasso to microarray gene expression datasets, where we used information from the Pathway Commons (PC) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as prior information for the network reconstruction, and successfully identified network hub genes associated with clinical outcome in cancer patients. Availability: The source code is available at http://nba.uth.tmc.edu/homepage/liu/pLasso . Contact: Yin.Liu@uth.tmc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 4
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    Dicer-independent processing of short hairpin RNAs (2013)
    Oxford University Press
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    Publication Date: 2013-04-02
    Description: Short hairpin RNAs (shRNAs) are widely used to induce RNA interference (RNAi). We tested a variety of shRNAs that differed in stem length and terminal loop size and revealed strikingly different RNAi activities and shRNA-processing patterns. Interestingly, we identified a specific shRNA design that uses an alternative Dicer-independent processing pathway. Detailed analyses indicated that a short shRNA stem length is critical for avoiding Dicer processing and activation of the alternative processing route, in which the shRNA is incorporated into RISC and processed by the AGO2-mediated slicer activity. Such alternatively processed shRNAs (AgoshRNAs) yield only a single RNA strand that effectively induces RNAi, whereas conventional shRNA processing results in an siRNA duplex of which both strands can trigger RNAi. Both the processing and subsequent RNAi activity of these AgoshRNAs are thus mediated by the RISC-component AGO2. These results have important implications for the future design of more specific RNAi therapeutics.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts (2013)
    Oxford University Press
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    Publication Date: 2013-09-26
    Description: It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, Coding-Non-Coding Index (CNCI), by profiling adjoining nucleotide triplets to effectively distinguish protein-coding and non-coding sequences independent of known annotations. CNCI is effective for classifying incomplete transcripts and sense–antisense pairs. The implementation of CNCI offered highly accurate classification of transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, that demonstrated gene evolutionary divergence between vertebrates, and invertebrates, or between plants, and provided a long non-coding RNA catalog of orangutan. CNCI software is available at http://www.bioinfo.org/software/cnci .
    Keywords: Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Detecting and understanding genetic and structural features in HIV-1 B subtype V3 underlying HIV-1 co-receptor usage (2013)
    Oxford University Press
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    Publication Date: 2013-02-13
    Description: Motivation: To define V3 genetic elements and structural features underlying different HIV-1 co-receptor usage in vivo . Results: By probabilistically modeling mutations in the viruses isolated from HIV-1 B subtype patients, we present a unique statistical procedure that would first identify V3 determinants associated with the usage of different co-receptors cooperatively or independently, and then delineate the complicated interactions among mutations functioning cooperatively. We built a model based on dual usage of CXCR4 and CCR5 co-receptors. The molecular basis of our statistical predictions is further confirmed by phenotypic and molecular modeling analyses. Our results provide new insights on molecular basis of different HIV-1 co-receptor usage. This is critical to optimize the use of genotypic tropism testing in clinical practice and to obtain molecular-implication for design of vaccine and new entry-inhibitors. Contact: jing.zhang.jz349@yale.edu or cf.perno@uniroma2.it Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 7
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    NGSUtils: a software suite for analyzing and manipulating next-generation sequencing datasets (2013)
    Oxford University Press
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    Publication Date: 2013-02-13
    Description: : NGSUtils is a suite of software tools for manipulating data common to next-generation sequencing experiments, such as FASTQ, BED and BAM format files. These tools provide a stable and modular platform for data management and analysis. Availability and implementation: NGSUtils is available under a BSD license and works on Mac OS X and Linux systems. Python 2.6+ and virtualenv are required. More information and source code may be obtained from the website: http://ngsutils.org . Contact: yunliu@iupui.edu Supplemental information: Supplementary data are available at Bioinformatics online.
    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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    Improvement of an aquaculture site-selection model for Japanese kelp (Saccharina japonica) in southern Hokkaido, Japan: an application for the impacts of climate events (2013)
    Oxford University Press
    Details
    Publication Date: 2013-10-15
    Description: Liu, Y., Saitoh, S-I., Radiarta, I. N., Isada, T., Hirawake, T., Mizuta, H., and Yasui, H. 2013. Improvement of an aquaculture site-selection model for Japanese kelp ( Saccharina japonica ) in southern Hokkaido, Japan: an application for the impacts of climate events. – ICES Journal of Marine Science, 70: . Japanese kelp ( Saccharina japonica ) is one of the most valuable cultured and harvested kelp species in Japan. In this study, we added a physical parameter, sea surface nitrate (SSN) estimated from satellite remote sensing data, to develop a suitable aquaculture site-selection model (SASSM) for hanging cultures of Japanese kelp in southern Hokkaido, Japan. The local algorithm to estimate SSN was developed using satellite measurements of sea surface temperature and chlorophyll-a. We found a high correlation between satellite- and ship-measured data ( r 2 = 0.87, RMSE = 1.39). Multi-criteria evaluation was adapted to the SASSM to rank sites on a scale of 1 (least suitable) to 8 (most suitable). We found that 64.4% of the areas were suitable (score above 7). Minamikayabe was identified as the most suitable area, and Funka Bay also contained potential aquaculture sites. In addition, we examined the impact of El Niño/La Niña–Southern Oscillation (ENSO) events on Japanese kelp aquaculture and site suitability from 2003–2010. During El Niño events, the number of suitable areas (scores 7 and 8) decreased significantly, indicating that climatic conditions should be considered for future development of marine aquaculture.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press
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  • 9
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    Deciphering the 8q24.21 association for glioma (2013)
    Oxford University Press
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    Publication Date: 2013-05-14
    Description: We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 ( P = 2.24 x 10 –38 ) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours ( P = 1.07 x 10 –67 ). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 x 10 –28 ). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 ( P = 2.31 x 10 –94 ). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality . These data provide additional insights into the aetiological basis of glioma development.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    Phosphorylation of the alternative mRNA splicing factor 45 (SPF45) by Clk1 regulates its splice site utilization, cell migration and invasion (2013)
    Oxford University Press
    Details
    Publication Date: 2013-05-04
    Description: Alternative mRNA splicing is a mechanism to regulate protein isoform expression and is regulated by alternative splicing factors. The alternative splicing factor 45 (SPF45) is overexpressed in cancer, although few biological effects of SPF45 are known, and few splicing targets have been identified. We previously showed that Extracellular Regulated Kinase 2 (ERK2) phosphorylation of SPF45 regulates cell proliferation and adhesion to fibronectin. In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues. Clk1 expression enhanced, whereas Clk1 inhibition reduced, SPF45-induced exon 6 exclusion from Fas mRNA. Mutational analysis of the Clk1 phosphorylation sites on SPF45 showed both positive and negative regulation of splicing, with a net effect of inhibiting SPF45-induced exon 6 exclusion, correlating with reduced Fas mRNA binding. However, Clk1 enhanced SPF45 protein expression, but not mRNA expression, whereas inhibition of Clk1 increased SPF45 degradation through a proteasome-dependent pathway. Overexpression of SPF45 or a phospho-mimetic mutant, but not a phospho-inhibitory mutant, stimulated ovarian cancer cell migration and invasion, correlating with increased fibronectin expression, ERK activation and enhanced splicing and phosphorylation of full-length cortactin. Our results demonstrate for the first time that SPF45 overexpression enhances cell migration and invasion, dependent on biochemical regulation by Clk1.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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