BACKGROUND: Some transcription factors, MYC for example, bind sites of potentially methylated DNA. This may increase binding specificity as such sites are (1) highly under-represented in the genome, and (2) offer additional, tissue specific information in the form of hypo- or hyper-methylation. Fortunately, bisulfite sequencing data can be used to investigate this phenomenon. METHOD: We developed MethylSeqLogo, an extension of sequence logos which includes new elements to indicate DNA methylation and under-represented dimers in each position of a set binding sites. Our method displays information from both DNA strands, and takes into account the sequence context (CpG or other) and genome region (promoter versus whole genome) appropriate to properly assess the expected background dimer frequency and level of methylation. MethylSeqLogo preserves sequence logo semantics-the relative height of nucleotides within a column represents their proportion in the binding sites, while the absolute height of each column represents information (relative entropy) and the height of all columns added together represents total information RESULTS: We present figures illustrating the utility of using MethylSeqLogo to summarize data from several CpG binding transcription factors. The logos show that unmethylated CpG binding sites are a feature of transcription factors such as MYC and ZBTB33, while some other CpG binding transcription factors, such as CEBPB, appear methylation neutral. CONCLUSIONS: Our software enables users to explore bisulfite and ChIP sequencing data sets-and in the process obtain publication quality figures.

MOTIVATION: Alignment-free, k-mer based genotyping methods are a fast alternative to alignment-based methods and are particularly well suited for genotyping larger cohorts. The sensitivity of algorithms, that work with k-mers, can be increased by using spaced seeds, however, the application of spaced seeds in k-mer based genotyping methods has not been researched yet. RESULTS: We add a spaced seeds functionality to the genotyping software PanGenie and use it to calculate genotypes. This significantly improves sensitivity and F-score when genotyping SNPs, indels, and structural variants on reads with low (5×) and high (30×) coverage. Improvements are greater than what could be achieved by just increasing the length of contiguous k-mers. Effect sizes are particularly large for low coverage data. If applications implement effective algorithms for hashing of spaced k-mers, spaced k-mers have the potential to become an useful technique in k-mer based genotyping. AVAILABILITY AND IMPLEMENTATION: The source code of our proposed tool MaskedPanGenie is openly available on https://github.com/hhaentze/MaskedPangenie.

Abstract Science teams for rover-based planetary exploration missions like the Mars Science Laboratory Curiosity rover have limited time for analyzing new data before making decisions about follow-up observations. There is a need for systems that can rapidly and intelligently extract information from planetary instrument datasets and focus attention on the most promising or novel observations. Several novelty detection methods have been explored in prior work for three-channel color images and non-image datasets, but few have considered multispectral or hyperspectral image datasets for the purpose of scientific discovery. We compared the performance of four novelty detection methods—Reed Xiaoli (RX) detectors, principal component analysis (PCA), autoencoders, and generative adversarial networks (GANs)—and the ability of each method to provide explanatory visualizations to help scientists understand and trust predictions made by the system. We show that pixel-wise RX and autoencoders trained with structural similarity (SSIM) loss can detect morphological novelties that are not detected by PCA, GANs, and mean squared error autoencoders, but that the latter methods are better suited for detecting spectral novelties—i.e., the best method for a given setting depends on the type of novelties that are sought. Additionally, we find that autoencoders provide the most useful explanatory visualizations for enabling users to understand and trust model detections, and that existing GAN approaches to novelty detection may be limited in this respect.

Starting a professional society is not something that should be entered into lightly: it requires work and dedication that can detract from your research projects and other career objectives [15]. It certainly should not be attempted on your own. But there are many potential benefits and rewards in terms of promoting the profile of your discipline (which, in turn, can affect your grant success), boosting your own profile, developing useful management and leadership skills, finding mentors, and forming essential contacts and partnerships, as science is becoming increasingly collaborative. A successful society will be a source of lifelong learning and new ideas, will open up career opportunities for students and investigators, and will provide a much stronger voice for your discipline than an isolated scientist.

GIW/InCoB2015 the joint 26th International Conference on Genome Informatics (GIW) and 14th International Conference on Bioinformatics (InCoB) held in Tokyo, September 9-11, 2015 was attended by over 200 delegates. Fifty-one out of 89 oral presentations were based on research articles accepted for publication in four BMC journal supplements and three other journals. Sixteen articles in this supplement and six articles in the BMC Systems Biology GIW/InCoB2015 Supplement are covered by this introduction. The topics range from genome informatics, protein structure informatics, image analysis to biological networks and biomarker discovery.

The papers in this special section were presented at the 2014 International Conference on Genome Informatics (GIW).

In this issue, we present a collection of papers inspired by ISCB-Asia/SCCG 2012, an international conference on bioinformatics co-organized by the International Society of Computational Biology and BGI, known for their Sequencing Center near the conference site in Shenzhen, China. The issue begins at the whiteboard fastidiously counting bits, gradually moves into the more abstract world of inferring various kinds of gene networks and ends near the clinic reviewing methods to detect diabetes biomarkers and cancer driver mutations. In the first paper, Shrestha et al. give the reader a look ‘under-the-hood’ at how to efficiently construct suffix arrays, a data structure forming the basis for most methods used in the initial processing of high-throughput sequencing data. In the second paper, Gromiha & Ou review databases, online resources and sequence analysis techniques to characterize membrane proteins primarily from their amino acid sequence. In the third paper, Vreven et al. compare methods to predict protein–protein complexes from sequence. The next three papers focus on the inference of various kinds of networks. B. Chen et al. review methods for inferring protein–protein interaction networks from a collection of (possibly error-prone) protein–protein interaction pairs. Maetschke et al. show a little teaching can go a long way in their comparison of supervised versus unsupervised inference methods for gene regulatory networks. Kim et al. provide a comprehensive review of methods for inferring dynamic networks from time course data. Both B. Chen et al. and Kim et al. discuss the decomposition of interactions in spatial (subcellular localization) and temporal dimensions. The last two papers focus on medical applications. Li et al. review the dynamical network biomarkers method to identify genes marking pre-disease to disease transition from time course expression data, applying the method on animal models of type 2 diabetes as a test case. Finally, Zhang et al. bring us back to the genome by reviewing methods to distinguish driver mutations from passenger mutations in cancer. Despite the broad range of topics covered, several issues are encountered in multiple papers. Among the common issues are low concordance between different prediction methods, high variance in performance across samples and the difficulties in constructing realistic and informative performance benchmarks. Another common thread is the need to integrate highly diverse sources of information to produce biologically relevant results. One clear conclusion is that we have a long road ahead of us before our discipline fully catches up to the potential insights, which high-throughput sequencing promises. Even simply constructing an efficient data structure to hold sequence data is nontrivial, predicting a single interaction pair challenging, and automatically inferring genome-scale gene networks is currently infeasible. However, this issue also gives us a glimpse of what is waiting for us at the end of that road—improved health for mankind.

The suffix array and its variants are text-indexing data structures that have become indispensable in the field of bioinformatics. With the uninitiated in mind, we provide an accessible exposition of the SA-IS algorithm, which is the state of the art in suffix array construction. We also describe DisLex, a technique that allows standard suffix array construction algorithms to create modified suffix arrays designed to enable a simple form of inexact matching needed to support 'spaced seeds' and 'subset seeds' used in many biological applications.

The International Society for Computational Biology, ISCB, organizes the largest event in the field of computational biology and bioinformatics, namely the annual international conference on Intelligent Systems for Molecular Biology, the ISMB. This year at ISMB 2012 in Long Beach, ISCB celebrated the 20th anniversary of its flagship meeting. ISCB is a young, lean and efficient society that aspires to make a significant impact with only limited resources. Many constraints make the choice of venues for ISMB a tough challenge. Here, we describe those challenges and invite the contribution of ideas for solutions.

In this paper we apply machine learning to the task of predicting transcription factor binding sites by combining information on multiple forms of chromatin modification with the binding strength DNA site predicted by a position weight matrix. We additionally explore the effect of incorporating auxiliary features such as the distance of the site to the nearest gene's transcription start site and the degree to which the site is conserved among related species. We approach the task as a classification problem, and show that both Naïve Bayes and Random Forests can provide substantial increases in the accuracy of predicted binding sites. Our results extend previous work which simply filtered candidate sites based on H3K4Me3 chromatin modification scores. In addition we apply feature selection to explore which forms of chromatin modification and which auxiliary features have predictive value for which transcription factors.

BACKGROUND: Genome sequence alignments form the basis of much research. Genome alignment depends on various mundane but critical choices, such as how to mask repeats and which score parameters to use. Surprisingly, there has been no large-scale assessment of these choices using real genomic data. Moreover, rigorous procedures to control the rate of spurious alignment have not been employed. RESULTS: We have assessed 495 combinations of score parameters for alignment of animal, plant, and fungal genomes. As our gold-standard of accuracy, we used genome alignments implied by multiple alignments of proteins and of structural RNAs. We found the HOXD scoring schemes underlying alignments in the UCSC genome database to be far from optimal, and suggest better parameters. Higher values of the X-drop parameter are not always better. E-values accurately indicate the rate of spurious alignment, but only if tandem repeats are masked in a non-standard way. Finally, we show that gamma-centroid (probabilistic) alignment can find highly reliable subsets of aligned bases. CONCLUSIONS: These results enable more accurate genome alignment, with reliability measures for local alignments and for individual aligned bases. This study was made possible by our new software, LAST, which can align vertebrate genomes in a few hours http://last.cbrc.jp/.

Abstract Summary: The establishment and rapid expansion of microarray databases has created a need for new search tools. Here we present CellMontage, the first server for expression profile similarity search over a large database—69 000 microarray experiments derived from NCBI's; GEO site. CellMontage provides a novel, content-based search engine for accessing gene expression data. Microarray experiments with similar overall expression to a user-provided expression profile (e.g. microarray experiment) are computed and displayed—usually within 20 s. The core search engine software is downloadable from the site. Availability: http://cellmontage.cbrc.jp/ Contact: [email protected] Supplementary information: http://cellmontage.cbrc.jp/supplementary/

BACKGROUND: Prediction of human cell response to anti-cancer drugs (compounds) from microarray data is a challenging problem, due to the noise properties of microarrays as well as the high variance of living cell responses to drugs. Hence there is a strong need for more practical and robust methods than standard methods for real-value prediction. RESULTS: We devised an extended version of the off-subspace noise-reduction (de-noising) method to incorporate heterogeneous network data such as sequence similarity or protein-protein interactions into a single framework. Using that method, we first de-noise the gene expression data for training and test data and also the drug-response data for training data. Then we predict the unknown responses of each drug from the de-noised input data. For ascertaining whether de-noising improves prediction or not, we carry out 12-fold cross-validation for assessment of the prediction performance. We use the Pearson's correlation coefficient between the true and predicted response values as the prediction performance. De-noising improves the prediction performance for 65% of drugs. Furthermore, we found that this noise reduction method is robust and effective even when a large amount of artificial noise is added to the input data. CONCLUSION: We found that our extended off-subspace noise-reduction method combining heterogeneous biological data is successful and quite useful to improve prediction of human cell cancer drug responses from microarray data.

MOTIVATION: Discriminating outer membrane proteins from other folding types of globular and membrane proteins is an important task both for dissecting outer membrane proteins (OMPs) from genomic sequences and for the successful prediction of their secondary and tertiary structures. RESULTS: We have developed a method based on support vector machines using amino acid composition and residue pair information. Our approach with amino acid composition has correctly predicted the OMPs with a cross-validated accuracy of 94% in a set of 208 proteins. Further, this method has successfully excluded 633 of 673 globular proteins and 191 of 206 alpha-helical membrane proteins. We obtained an overall accuracy of 92% for correctly picking up the OMPs from a dataset of 1087 proteins belonging to all different types of globular and membrane proteins. Furthermore, residue pair information improved the accuracy from 92 to 94%. This accuracy of discriminating OMPs is higher than that of other methods in the literature, which could be used for dissecting OMPs from genomic sequences. AVAILABILITY: Discrimination results are available at http://tmbeta-svm.cbrc.jp.

TACO is a template library that implements higher-order parallel operations on distributed object sets by means of reusable topology classes and C++ function templates. We discuss an experimental application that exploits TACO's distributed object groups and collective operations for computing the similarity between groups of molecular sequences, a computationally intensive core problem in molecular biology research. In particular we show how TACO's distributed collections can be conveniently combined with well known concepts found in the C++ standard template library (STL) to solve matching and sorting problems effectively on distributed hardware platforms. The resulting implementation is concise and gives excellent parallel performance on PC- and workstation clusters.