BACKGROUND: DNA methylation is an important epigenetic modification that is known to regulate gene expression. Whole-genome bisulfite sequencing (WGBS) is a powerful method for studying cytosine methylation in a whole genome. However, it is difficult to obtain methylation profiles using the WGBS raw reads and is necessary to be proficient in all types of bioinformatic tools for the study of DNA methylation. In addition, recent end-to-end pipelines for DNA methylation analyses are not sufficient for addressing those difficulties. RESULTS: Here we present msPIPE, a pipeline for DNA methylation analyses with WGBS data seamlessly connecting all the required tasks ranging from data pre-processing to multiple downstream DNA methylation analyses. The msPIPE can generate various methylation profiles to analyze methylation patterns in the given sample, including statistical summaries and methylation levels. Also, the methylation levels in the functional regions of a genome are computed with proper annotation. The results of methylation profiles, hypomethylation, and differential methylation analysis are plotted in publication-quality figures. The msPIPE can be easily and conveniently used with a Docker image, which includes all dependent packages and software related to DNA methylation analyses. CONCLUSION: msPIPE is a new end-to-end pipeline designed for methylation calling, profiling, and various types of downstream DNA methylation analyses, leading to the creation of publication-quality figures. msPIPE allows researchers to process and analyze the WGBS data in an easy and convenient way. It is available at https://github.com/jkimlab/msPIPE and https://hub.docker.com/r/jkimlab/mspipe .

BACKGROUND: Microorganisms are important occupants of many different environments. Identifying the composition of microbes and estimating their abundance promote understanding of interactions of microbes in environmental samples. To understand their environments more deeply, the composition of microorganisms in environmental samples has been studied using metagenomes, which are the collections of genomes of the microorganisms. Although many tools have been developed for taxonomy analysis based on different algorithms, variability of analysis outputs of existing tools from the same input metagenome datasets is the main obstacle for many researchers in this field. RESULTS: Here, we present a novel meta-analysis tool for metagenome taxonomy analysis, called TAMA, by intelligently integrating outputs from three different taxonomy analysis tools. Using an integrated reference database, TAMA performs taxonomy assignment for input metagenome reads based on a meta-score by integrating scores of taxonomy assignment from different taxonomy classification tools. TAMA outperformed existing tools when evaluated using various benchmark datasets. It was also successfully applied to obtain relative species abundance profiles and difference in composition of microorganisms in two types of cheese metagenome and human gut metagenome. CONCLUSION: TAMA can be easily installed and used for metagenome read classification and the prediction of relative species abundance from multiple numbers and types of metagenome read samples. TAMA can be used to more accurately uncover the composition of microorganisms in metagenome samples collected from various environments, especially when the use of a single taxonomy analysis tool is unreliable. TAMA is an open source tool, and can be downloaded at https://github.com/jkimlab/TAMA.

BACKGROUND: Thanks to the recent advancements in next-generation sequencing (NGS) technologies, large amount of genomic data, which are short DNA sequences known as reads, has been accumulating. Diverse assemblers have been developed to generate high quality de novo assemblies using the NGS reads, but their output is very different because of algorithmic differences. However, there are not properly structured measures to show the similarity or difference in assemblies. RESULTS: We developed a new measure, called the GMASS score, for comparing two genome assemblies in terms of their structure. The GMASS score was developed based on the distribution pattern of the number and coverage of similar regions between a pair of assemblies. The new measure was able to show structural similarity between assemblies when evaluated by simulated assembly datasets. The application of the GMASS score to compare assemblies in recently published benchmark datasets showed the divergent performance of current assemblers as well as its ability to compare assemblies. CONCLUSION: The GMASS score is a novel measure for representing structural similarity between two assemblies. It will contribute to the understanding of assembly output and developing de novo assemblers.

BACKGROUND: Advances in sequencing technologies have facilitated large-scale comparative genomics based on whole genome sequencing. Constructing and investigating conserved genomic regions among multiple species (called synteny blocks) are essential in the comparative genomics. However, they require significant amounts of computational resources and time in addition to bioinformatics skills. Many web interfaces have been developed to make such tasks easier. However, these web interfaces cannot be customized for users who want to use their own set of genome sequences or definition of synteny blocks. RESULTS: To resolve this limitation, we present mySyntenyPortal, a stand-alone application package to construct websites for synteny block analyses by using users' own genome data. mySyntenyPortal provides both command line and web-based interfaces to build and manage websites for large-scale comparative genomic analyses. The websites can be also easily published and accessed by other users. To demonstrate the usability of mySyntenyPortal, we present an example study for building websites to compare genomes of three mammalian species (human, mouse, and cow) and show how they can be easily utilized to identify potential genes affected by genome rearrangements. CONCLUSIONS: mySyntenyPortal will contribute for extended comparative genomic analyses based on large-scale whole genome sequences by providing unique functionality to support the easy creation of interactive websites for synteny block analyses from user's own genome data.

Rapid advances in biology demand new tools for more active research dissemination and engaged teaching. This paper presents Synteny Explorer, an interactive visualization application designed to let college students explore genome evolution of mammalian species. The tool visualizes synteny blocks: segments of homologous DNA shared between various extant species that can be traced back or reconstructed in extinct, ancestral species. We take a karyogram-based approach to create an interactive synteny visualization, leading to a more appealing and engaging design for undergraduate-level genome evolution education. For validation, we conduct three user studies: two focused studies on color and animation design choices and a larger study that performs overall system usability testing while comparing our karyogram-based designs with two more common genome mapping representations in an educational context. While existing views communicate the same information, study participants found the interactive, karyogram-based views much easier and likable to use. We additionally discuss feedback from biology and genomics faculty, who judge Synteny Explorer's fitness for use in classrooms.

SUMMARY: We developed PSAR-Align, a multiple sequence realignment tool that can refine a given multiple sequence alignment based on suboptimal alignments generated by probabilistic sampling. Our evaluation demonstrated that PSAR-Align is able to improve the results from various multiple sequence alignment tools. AVAILABILITY AND IMPLEMENTATION: The PSAR-Align source code (implemented mainly in C++) is freely available for download at http://bioen-compbio.bioen.illinois.edu/PSAR-Align.

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-coding sequences if provided with the true alignments. CONCLUSION: We have developed a method to generate benchmarks for multiple alignments of Drosophila non-coding sequences, and shown it to be more realistic than traditional benchmarks. Apart from helping to select the most effective tools, these benchmarks will help practitioners of comparative genomics deal with the effects of alignment errors, by providing accurate estimates of the extent of these errors.

We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score for motif scanning, the use of different scores for predicting targets of different motifs, and new ways to deal with redundancies among significant motif-function associations. This framework is applied to the recently sequenced genome of the jewel wasp, Nasonia vitripennis, making use of the existing knowledge of motifs and gene annotations in another insect genome, that of the fruitfly. The framework uses cross-species comparison to improve the specificity of its predictions, and does so without relying upon non-coding sequence alignment. It is therefore well suited for comparative genomics across large evolutionary divergences, where existing alignment-based methods are not applicable. We also apply the framework to find motifs associated with socially regulated gene sets in the honeybee, Apis mellifera, using comparisons with Nasonia, a solitary species, to identify honeybee-specific associations.

Simulation-based functional verification is characterized by two inherently conflicting targets: the signal visibility and simulation performance. Achieving a proper trade-off between these two targets is of paramount importance. Even though HDL simulators are the most widely used verification platform at the RTL and gate level, their major drawback is the low performance in verifying complex SOCs, especially when the high visibility over the design under verification is required. This paper presents a new, fast simulation method as an effective way to achieve both high simulation speed and full signal visibility. It is based on an original two-pass simulation approach. During the 1stpass, with the simulation running at full speed, a set of design states is saved periodically at predetermined checkpoints. During the 2ndpass, another simulation is performed, using any of saved checkpoints and providing 100% signal visibility for debugging. Our method differs from the traditional simulation snapshot approach in the amount and the way the design state is saved. Experimental results show significant speed-up compared to existing traditional simulation methods while maintaining 100% visibility.

Ranking has been popularly used for intelligent data retrieval in both database and machine learning communities. Recently, there were studies on integrating these two approaches to support soft queries, based on a user's sense of relevance and preference, for ranking with numerical attributes. However, in real life, it is desirable to use categorical attributes together with numerical ones in ranking. For example, when buying a car, categorical attributes, such as make, model, color, and equipments, are considered as significant factors as numerical attributes, such as price and year. Meanwhile, users often do not have sufficient domain knowledge at formulating an effective selection query over categories, whereas rank formulation is even more challenging as categories have no inherent ordering. In this paper, we propose a framework PerRank (Personalized Ranking with Categorical and Numerical Attributes) to support personalized ranking with both categorical and numerical attributes for soft queries. For an efficient computation, we developed an algorithm CAC (Clustering-based Attribute Construction) which makes use of a clustering method. Extensive experiments show CAC is effective and efficient at supporting ranking with both categorical and numerical attributes for soft queries.

MOTIVATION: A quantitative study of molecular evolutionary events such as substitutions, insertions and deletions from closely related genomes requires (1) an accurate multiple sequence alignment program and (2) a method to annotate the insertions and deletions that explain the 'gaps' in the alignment. Although the former requirement has been extensively addressed, the latter problem has received little attention, especially in a comprehensive probabilistic framework. RESULTS: Here, we present Indelign, a program that uses a probabilistic evolutionary model to compute the most likely scenario of insertions and deletions consistent with an input multiple alignment. It is also capable of modifying the given alignment so as to obtain a better agreement with the evolutionary model. We find close to optimal performance and substantial improvement over alternative methods, in tests of Indelign on synthetic data. We use Indelign to analyze regulatory sequences in Drosophila, and find an excess of insertions over deletions, which is different from what has been reported for neutral sequences. AVAILABILITY: The Indelign program may be downloaded from the website http://veda.cs.uiuc.edu/indelign/ SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online.

Using a variable scaling factor (VSF), a modified enhanced max-log-maximum a posteriori (EMLMAP) algorithm is proposed to improve the performance of the conventional EMLMAP algorithm which uses a fixed SF. The VSF, maximising the mutual information exchanged between component decoders in a turbo decoder, is adaptively varied with a priori information of each component decoder. For a large size of interleaver, it is shown that the proposed algorithm improves the bit error rate performance and speed of decoding convergence of the conventional EMLMAP algorithm. The improved speed of the decoding convergence reduces the average number of iterations and results in low-power implementations of a turbo decoder.