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Improvement of alignment accuracy utilizing sequentially conserved motifs

BMC BIOINFORMATICS 2004年第1期5卷 167-167页

作者： Chakrabarti, S Bhardwaj, N Anand, PA Sowdhamini, R Natl Ctr Biol Sci TIFR Bangalore 560065 Karnataka India Indian Inst Technol Dept Chem Engn Bombay 400076 Maharashtra India Int Inst Informat Technol MSIT Hyderabad Andhra Pradesh India

Background: Multiple sequence alignment algorithms are very important tools in molecular biology today. Accurate alignment of proteins is central to several areas such as homology modelling, docking studies, understanding evolutionary trends and study of structure-function relationships. In recent times, improvement of existing progressing programs and implementation of new iterative algorithms have made a significant change in this field. Results: We report an alignment algorithm that combines progressive dynamic algorithm, local substructure alignment and iterative refinement to achieve an improved, user-interactive tool. Large-scale benchmarking studies show that this FMALIGN server produces alignments that, aside from preservation of functional and structural conservation, have accuracy comparable to other popular multiple alignment programs. Conclusions: The FMALIGN server allows the user to fix conserved regions in equivalent position in the alignment thereby reducing the chance of global misalignment to a great extent. FMALIGN is available at http://***/FMALIGN/***.

关键词： alignment Algorithm alignment program Unweighted Pair Group Method With Arithmetic Iterative Refinement Reference alignment

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CGAT: a comparative genome analysis tool for visualizing alignments in the analysis of complex evolutionary changes between closely related genomes

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BMC BIOINFORMATICS 2006年第1期7卷 472-472页

作者： Uchiyama, Ikuo Higuchi, Toshio Kobayashi, Ichizo Natl Inst Nat Sci Natl Inst Basic Biol Okazaki Aichi 4448585 Japan INTEC Web & Genome Informat Corp Koto Ku Tokyo 1360075 Japan Univ Tokyo Dept Med Genome Sci Grad Sch Frontier Sci Minato Ku Tokyo 1088639 Japan Univ Tokyo Inst Med Sci Minato Ku Tokyo 1088639 Japan Univ Tokyo Grad Program Biophys & Biochem Grad Sch Sci Minato Ku Tokyo Japan

Background: The recent accumulation of closely related genomic sequences provides a valuable resource for the elucidation of the evolutionary histories of various organisms. However, although numerous alignment calculation and visualization tools have been developed to date, the analysis of complex genomic changes, such as large insertions, deletions, inversions, translocations and duplications, still presents certain difficulties. Results: We have developed a comparative genome analysis tool, named CGAT, which allows detailed comparisons of closely related bacteria-sized genomes mainly through visualizing middle-to-large-scale changes to infer underlying mechanisms. CGAT displays precomputed pairwise genome alignments on both dotplot and alignment viewers with scrolling and zooming functions, and allows users to move along the pre-identified orthologous alignments. Users can place several types of information on this alignment, such as the presence of tandem repeats or interspersed repetitive sequences and changes in G+C contents or codon usage bias, thereby facilitating the interpretation of the observed genomic changes. In addition to displaying precomputed alignments, the viewer can dynamically calculate the alignments between specified regions;this feature is especially useful for examining the alignment boundaries, as these boundaries are often obscure and can vary between programs. Besides the alignment browser functionalities, CGAT also contains an alignment data construction module, which contains various procedures that are commonly used for pre- and post-processing for large-scale alignment calculation, such as the split-and-merge protocol for calculating long alignments, chaining adjacent alignments, and ortholog identification. Indeed, CGAT provides a general framework for the calculation of genome-scale alignments using various existing programs as alignment engines, which allows users to compare the outputs of different alignment programs. Earlier ver

关键词： Codon Usage Bias alignment program Segment Pair Feature Segment Annotation Track

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ContextMap 2: fast and accurate context-based RNA-seq mapping

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BMC BIOINFORMATICS 2015年第1期16卷 1-15页

作者： Bonfert, Thomas Kirner, Evelyn Csaba, Gergely Zimmer, Ralf Friedel, Caroline C. Univ Munich Inst Informat D-80333 Munich Germany

Background: Mapping of short sequencing reads is a crucial step in the analysis of RNA sequencing (RNA-seq) data. ContextMap is an RNA-seq mapping algorithm that uses a context-based approach to identify the best alignment for each read and allows parallel mapping against several reference genomes. Results: In this article, we present ContextMap 2, a new and improved version of ContextMap. Its key novel features are: (i) a plug-in structure that allows easily integrating novel short read alignment programs with improved accuracy and runtime;(ii) context-based identification of insertions and deletions (indels);(iii) mapping of reads spanning an arbitrary number of exons and indels. ContextMap 2 using Bowtie, Bowtie 2 or BWA was evaluated on both simulated and real-life data from the recently published RGASP study. Conclusions: We show that ContextMap 2 generally combines similar or higher recall compared to other state-of-the-art approaches with significantly higher precision in read placement and junction and indel prediction. Furthermore, runtime was significantly lower than for the best competing approaches. ContextMap 2 is freely available at http://***/ContextMap.

关键词： Splice Site Splice Junction alignment program Seed Length Read alignment

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SinicView: A visualization environment for comparisons of multiple nucleotide sequence alignment tools

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BMC BIOINFORMATICS 2006年第1期7卷 103-103页

作者： Shih, ACC Lee, DT Lin, L Peng, CL Chen, SH Wu, YW Wong, CY Chou, MY Shiao, TC Hsieh, F Acad Sinica Inst Informat Sci Taipei 115 Taiwan Acad Sinica Genom Res Ctr Taipei 115 Taiwan

Background: Deluged by the rate and complexity of completed genomic sequences, the need to align longer sequences becomes more urgent, and many more tools have thus been developed. In the initial stage of genomic sequence analysis, a biologist is usually faced with the questions of how to choose the best tool to align sequences of interest and how to analyze and visualize the alignment results, and then with the question of whether poorly aligned regions produced by the tool are indeed not homologous or are just results due to inappropriate alignment tools or scoring systems used. Although several systematic evaluations of multiple sequence alignment (MSA) programs have been proposed, they may not provide a standard-bearer for most biologists because those poorly aligned regions in these evaluations are never discussed. Thus, a tool that allows cross comparison of the alignment results obtained by different tools simultaneously could help a biologist evaluate their correctness and accuracy. Results: In this paper, we present a versatile alignment visualization system, called SinicView, ( for Sequence-aligning INnovative and Interactive Comparison VIEWer), which allows the user to efficiently compare and evaluate assorted nucleotide alignment results obtained by different tools. SinicView calculates similarity of the alignment outputs under a fixed window using the sum-of-pairs method and provides scoring profiles of each set of aligned sequences. The user can visually compare alignment results either in graphic scoring profiles or in plain text format of the aligned nucleotides along with the annotations information. We illustrate the capabilities of our visualization system by comparing alignment results obtained by MLAGAN, MAVID, and MULTIZ, respectively. Conclusion: With SinicView, users can use their own data sequences to compare various alignment tools or scoring systems and select the most suitable one to perform alignment in the initial stage of sequence anal

关键词： Cystic Fibrosis Transmembrane Conductance Regulator Repetitive Element alignment program alignment Tool Stem Cell Leukemia

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Towards realistic benchmarks for multiple alignments of non-coding sequences

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BMC BIOINFORMATICS 2010年第1期11卷 54-54页

作者： Kim, Jaebum Sinha, Saurabh Univ Illinois Dept Comp Sci Urbana IL 61801 USA Univ Illinois Inst Genom Biol Urbana IL 61801 USA

Background: With the continued development of new computational tools for multiple sequence alignment, it is necessary today to develop benchmarks that aid the selection of the most effective tools. Simulation-based benchmarks have been proposed to meet this necessity, especially for non-coding sequences. However, it is not clear if such benchmarks truly represent real sequence data from any given group of species, in terms of the difficulty of alignment tasks. Results: We find that the conventional simulation approach, which relies on empirically estimated values for various parameters such as substitution rate or insertion/deletion rates, is unable to generate synthetic sequences reflecting the broad genomic variation in conservation levels. We tackle this problem with a new method for simulating non-coding sequence evolution, by relying on genome-wide distributions of evolutionary parameters rather than their averages. We then generate synthetic data sets to mimic orthologous sequences from the Drosophila group of species, and show that these data sets truly represent the variability observed in genomic data in terms of the difficulty of the alignment task. This allows us to make significant progress towards estimating the alignment accuracy of current tools in an absolute sense, going beyond only a relative assessment of different tools. We evaluate six widely used multiple alignment tools in the context of Drosophila non-coding sequences, and find the accuracy to be significantly different from previously reported values. Interestingly, the performance of most tools degrades more rapidly when there are more insertions than deletions in the data set, suggesting an asymmetric handling of insertions and deletions, even though none of the evaluated tools explicitly distinguishes these two types of events. We also examine the accuracy of two existing tools for annotating insertions versus deletions, and find their performance to be close to optimal in Drosophila non

关键词： Drosophila Species alignment program True alignment Root Sequence alignment Task

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Efficient digest of high-throughput sequencing data in a reproducible report

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BMC BIOINFORMATICS 2013年第Sup11期14卷 S3-S3页

作者： Zhang, Zhe Leipzig, Jeremy Sasson, Ariella Yu, Angela M. Perin, Juan C. Xie, Hongbo M. Sarmady, Mahdi Warren, Patrick V. White, Peter S. Childrens Hosp Philadelphia Ctr Biomed Informat Philadelphia PA 19104 USA Childrens Hosp Philadelphia Div Oncol Philadelphia PA USA Univ Penn Dept Pediat Perelman Sch Med Philadelphia PA 19104 USA

Background: High-throughput sequencing (HTS) technologies are spearheading the accelerated development of biomedical research. Processing and summarizing the large amount of data generated by HTS presents a nontrivial challenge to bioinformatics. A commonly adopted standard is to store sequencing reads aligned to a reference genome in SAM (Sequence alignment/Map) or BAM (Binary alignment/Map) files. Quality control of SAM/BAM files is a critical checkpoint before downstream analysis. The goal of the current project is to facilitate and standardize this process. Results: We developed bamchop, a robust program to efficiently summarize key statistical metrics of HTS data stored in BAM files, and to visually present the results in a formatted report. The report documents information about various aspects of HTS data, such as sequencing quality, mapping to a reference genome, sequencing coverage, and base frequency. Bamchop uses the R language and Bioconductor packages to calculate statistical matrices and the Sweave utility and associated LaTeX markup for documentation. Bamchop's efficiency and robustness were tested on BAM files generated by local sequencing facilities and the 1000 Genomes Project. Source code, instruction and example reports of bamchop are freely available from https://***/CBMi-BiG/bamchop. Conclusions: Bamchop enables biomedical researchers to quickly and rigorously evaluate HTS data by providing a convenient synopsis and user-friendly reports.

关键词： Read Count Sequencing Depth Sequencing Quality alignment program Bioconductor Project

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Conservation of regulatory elements between two species of Drosophila

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BMC BIOINFORMATICS 2003年第1期4卷 57-57页

作者： Emberly, E Rajewsky, N Siggia, ED Rockefeller Univ Ctr Studies Phys & Biol New York NY 10021 USA NYU Dept Biol New York NY 10003 USA

Background: One of the important goals in the post-genomic era is to determine the regulatory elements within the non-coding DNA of a given organism's genome. The identification of functional cis-regulatory modules has proven difficult since the component factor binding sites are small and the rules governing their arrangement are poorly understood. However, the genomes of suitably diverged species help to predict regulatory elements based on the generally accepted assumption that conserved blocks of genomic sequence are likely to be functional. To judge the efficacy of strategies that prefilter by sequence conservation it is important to know to what extent the converse assumption holds, namely that functional elements common to both species will fall within these conserved blocks. The recently completed sequence of a second Drosophila species provides an opportunity to test this assumption for one of the experimentally best studied regulatory networks in multicellular organisms, the body patterning of the fly embryo. Results: We find that 50%-70% of known binding sites reside in conserved sequence blocks, but these percentages are not greatly enriched over what is expected by chance. Finally, a computational genome-wide search in both species for regulatory modules based on clusters of binding sites suggests that genes central to the regulatory network are consistently recovered. Conclusions: Our results indicate that binding sites remain clustered for these "core modules" while not necessarily residing in conserved blocks. This is an important clue as to how regulatory information is encoded in the genome and how modules evolve.

关键词： Module Prediction alignment program Noncoding Sequence Body Patterning Interspecies Comparison

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Database of publicly available nucleotide sequences

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Genome Biology 2000年第1期1卷 1-4页

作者： Betts, Matthew

Publicly available nucleotide sequences, along with their associated annotations are available here.

关键词： Nucleotide Sequence Sequence Database Additional Tool alignment program Nucleotide Sequence Database

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