ALBERT

Description: Two drugs that were thought not to be of benefit in the later stages of Alzheimer's disease have been shown to hold back severe decline by four months

Description: Hopes dashed of personalised drug treatments after two-thirds of genetic mutations in the same tumour are found to vary from one biopsy to the next

Description: The magnitude 9 megaquake that shook the east coast of Japan in March 2011 reactivated dormant faults close to Fukushima's beleaguered nuclear reactors

Description: Drugs that clamp onto a pathogen's vital enzymes when they are at their most reactive can combat a range of infections

Description: Belgium, the Netherlands and Luxembourg all punch above their weight when it comes to scientific innovation - and career opportunities

Description: Creating a haven for science is no simple feat in the Philippines, a country where evolution and fossils are controversial topics

Description: As early humans expanded beyond hunter-gatherer groups, religion was the glue that held societies full of strangers together, says Ara Norenzayan

Description: Those who would dance on religion's grave are underestimating its staying power, says Robert N. McCauley

Description: Further to your Instant Expert on sleep (4 February), I found a way to maximise the efficiency of sleep cycles when in Antarctica during the...

Description: • The story about a fire at a Brazilian Antarctic base (3 March, p 5) should have said most bases use non-flammable building materials...

Description: Can't live with him, can't live without him. In a special series of articles we lay out a new vision that resets the terms of the debate

Description: What is dark matter? Or gravity? Why is the universe so smooth? There's a particle for every conundrum, say Valerie Jamieson and Richard Webb

Description: Your article on dingo conservation and the Azaria Chamberlain inquest (18 February, p 28) reminded me of a pup I bought for my daughter from...

Description: Ben Haller's letter (25 February, p 36) about your editorial on brain-eavesdropping (4 February, p 3) makes a reasonable point regarding the possible...

Description: Your item on Jurassic katydid calls suggests that sounds at 6. 4 kilohertz "can travel long distances" (11 February, p 18). In fact, there is...

Description: Animals thinking inside a virtual world can help us understand what can go wrong in the brain

Description: Clusters of cells instrumental in building complex brains have been found in a simple worm that barely has a brain at all

Description: The prehistoric sea-level rise long thought to have been caused by the ice sheet melting may actually have been down to local subsidence

Description: In The Emotional Life of Your Brain , Richard J. Davidson has devised simple surveys based on solid neuroscience to help you shape your own grey matter

Description: Religions are not literally true but neither are they total nonsense. Atheists need to reclaim the useful bits, Alain de Botton tells Graham Lawton

Description: In his new novel, The Sensorium of God , Stuart Clark catalogues the messy international and interpersonal politics at the time of Newton's breakthroughs

Description: Religions are not literally true but neither are they total nonsense. Alain de Botton explains why atheists need to reclaim the useful bits

Description: Our minds solve fundamental problems in a way that leaves a god-shaped space just waiting to be filled by religion, explains Justin L. Barrett

Description: Human interactions influence how technology turns out, and not always for the better, argues Henry Petroski in To Forgive Design

Description: Your report on electric racing cars mentions charging mats built into the track to allow inductive charging on the go, and suggests the mats be...

Description: In your lost scientific treasures article, you mentioned Damascus steel (4 February, p 40). This material was made from high-carbon "wootz" steel made in...

Description: The unusual four-winged dinosaur was coated with dark iridescent feathers – not all of them used for flight, it seems

Description: Circumcised men reduced their risk of prostate cancer by 15 per cent, but only if they had the operation before having sex for the first time

Description: Free apps spend most of their power sending targeted adverts – and can drain your cellphone battery in 90 minutes

Description: Facebook has the power of a nation state, but is not living up to its moral responsibilities, says former CNN bureau chief Rebecca MacKinnon

Description: This close-up of a pride of feasting lions was taken by armoured photographic robot as it trundled across the Masai Mara

Description: Whether an ultimate creator as envisaged by religion exists or not is a question that science can address, argues Victor J. Stenger

Description: After receiving injections of human embryonic stem cells, monkeys with tremors and rigidity were able to move smoothly

Description: Some snails survive inside bird guts for hours at a time, and travel hundreds of kilometres that way before popping out at the other end

Description: Rapid switch between neutrino flavours could herald experiments to explore early universe's preference for matter

Description: Why can everyone learn Portuguese? Is Twitter a trivialiser? A whistle-stop tour of our intellectual landscape in the company of Noam Chomsky

Description: Religions are not literally true but neither are they total nonsense. Alain de Botton explains why atheists need to reclaim the useful bits

Description: Political "microtargeting" via social media is a double-edged sword

Description: MRI and PET scans have revealed how the genetic condition affects brain development, and might one day help to predict symptoms of Williams syndrome

Description: The model of atoms as mini solar systems was supplanted by quantum fuzziness – now atoms have been forced to act more like the classical systems

Description: Attempts to fly drones in civilian airspace are a classic example of an irresistible force (innovation) meeting an immovable object (the law)

Description: Mind-reading technology notwithstanding, there is no prospect of anyone looking inside your skull without your consent

Description: A selection of the responses from the forensic scientists who took our survey

Description: Our survey of UK forensic scientists reveals that many are concerned that closure of the Forensic Science Service will lead to miscarriages of justice

Description: In The Joy of Sin , Simon Laham presents compelling evidence that indulging in your darker side need not necessarily be bad

Description: In Beautiful Souls , Eyal Press writes a beautiful narrative of whistle-blowers and refuseniks, but seeks in vain to pin down their psychological profile

Description: The "cuddle chemical" oxytocin bonds mothers to their babies and sniffing it makes adults nicer – but can also foster gloating and racism

Description: Nearly all our fresh water comes from obscure underground deposits – now satellites and radioactive isotopes are telling us how much we have to go round

Description: Imagine charging your cellphone from a meadow or harvesting electricity from rice paddies. The technology works, but can we make plant power a staple crop?

Description: I had no idea beetles could be such pests, as in the case of the bark beetle damaging North American forests (5 November 2011, p...

Description: In his letter, Brian Robinson says that, during a time of austerity, a hiatus in pursuit of the mysteries of the cosmos would not matter...

Description: • Saul (not Sam) Winstein was the champion of unconventional carbocation chemistry (21 January, p 34...

Description: Further to Michael Dowling's letter calling for the creation problem in cosmological theory to be left to philosophers rather than physicists like Stephen Hawking...

Description: Felicitas Arias of the International Bureau of Weights and Measures suggests we stop adding leap seconds to coordinated universal time (UTC), which is based on...

Description: Your feature on the idea of progress in evolution included palaeontologist Simon Conway Morris's suggestion that ice ages would have killed off the dinosaurs...

Description: Jesse Prinz offers that "philosophy tells us what is possible, and science tells us what is true" (21 January, p 26). This serves us well...

Description: Do British people know enough about the financial interests of those writing health articles? Time to toughen editorial codes, asks James Davies

Description: The unique pattern of your heartbeat could one day be used to encrypt hard drives and other electronics

Description: Australia has a long history of ecological disaster from alien species - so why is ecologist David Bowman proposing adding yet another?

Description: Books and formal papers make knowledge look finite, knowable. By embracing the unfinished, unfinishable forms of the web we are truer to the spirit of enquiry - and to the world we live in, says David Weinberger

Description: How the Lola-Drayson electric concept car gets its juice is even more impressive than its flat-out speed

Description: Parents and those newly head-over-heals show greater activation of brain areas related to parental attachment when they see a baby than single people

Description: A 15 kilometre-long swatche of seagrass off the coast of Spain is at least 80,000 years old, making it the oldest living organism that we know of on Earth

Description: A shortage of the drug methotrexate may put children with leukaemia at risk within weeks

Description: Regrowing our brain cells is one of the great hopes of modern medicine. But could this idea be based on wishful thinking?

Description: The elusive Casimir effect suggests we could use vacuum energy to move objects and make stuff – but can something really come from nothing?

Description: People with schizophrenia sometimes have small cerebellums – stress or diet may suppress its growth in a fetus, making this a possible factor in the illness

Description: Zapping the brain with a weak magnetic pulse can wipe out unwanted neural connections implicated in schizophrenia and autism, in mice at least

Description: A twist on the classic "trolley" psychology experiment suggests that our minds have two parallel moral systems, and they don't always agree

Description: Hypothetical particles that have been playing hide-and-seek with physicists for decades may finally be stepping into view

Description: Short, coordinated bursts of high-speed computing could speed up smartphones by a factor of 10

Description: Paper structures filled with air could lead to new "soft" robots that can handle delicate objects

Description: Tiny coral-like formations of salt sometimes sprout up on brickwork, and now researchers know why – which could help save delicate frescoes

Description: Motivation: High-throughput sequencing (HTS) technologies have made low-cost sequencing of large numbers of samples commonplace. An explosion in the type, not just number, of sequencing experiments has also taken place including genome re-sequencing, population-scale variation detection, whole transcriptome sequencing and genome-wide analysis of protein-bound nucleic acids. Results: We present Artemis as a tool for integrated visualization and computational analysis of different types of HTS datasets in the context of a reference genome and its corresponding annotation. Availability: Artemis is freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute websites: http://www.sanger.ac.uk/resources/software/artemis/ . Contact: artemis@sanger.ac.uk ; tjc@sanger.ac.uk

Description: : microRibonucleic acid (miRNAs) are small regulatory molecules that act by mRNA degradation or via translational repression. Although many miRNAs are ubiquitously expressed, a small subset have differential expression patterns that may give rise to tissue-specific complexes. Motivation: This work studies gene targeting patterns amongst miRNAs with differential expression profiles, and links this to control and regulation of protein complexes. Results: We find that, when a pair of miRNAs are not expressed in the same tissues, there is a higher tendency for them to target the direct partners of the same hub proteins. At the same time, they also avoid targeting the same set of hub-spokes. Moreover, the complexes corresponding to these hub-spokes tend to be specific and nonoverlapping. This suggests that the effect of miRNAs on the formation of complexes is specific. Contact: wongls@comp.nus.edu.sg Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Small interfering RNAs (siRNAs) are produced from much longer sequences of double-stranded RNA precursors through cleavage by Dicer or a Dicer-like protein. These small RNAs play a key role in genetic and epigenetic regulation; however, a full understanding of the mechanisms by which they operate depends on the characterization of the precursors from which they are derived. Results: High-throughput sequencing of small RNA populations allows the locations of the double-stranded RNA precursors to be inferred. We have developed methods to analyse small RNA sequencing data from multiple biological sources, taking into account replicate information, to identify robust sets of siRNA precursors. Our methods show good performance on both a set of small RNA sequencing data in Arabidopsis thaliana and simulated datasets. Availability: Our methods are available as the Bioconductor ( www.bioconductor.org ) package segmentSeq (version 1.5.6 and above). Contact: tjh48@cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Intrinsically disordered regions are key for the function of numerous proteins, and the scant available experimental annotations suggest the existence of different disorder flavors. While efficient predictions are required to annotate entire genomes, most existing methods require sequence profiles for disorder prediction, making them cumbersome for high-throughput applications. Results: In this work, we present an ensemble of protein disorder predictors called ESpritz. These are based on bidirectional recursive neural networks and trained on three different flavors of disorder, including a novel NMR flexibility predictor. ESpritz can produce fast and accurate sequence-only predictions, annotating entire genomes in the order of hours on a single processor core. Alternatively, a slower but slightly more accurate ESpritz variant using sequence profiles can be used for applications requiring maximum performance. Two levels of prediction confidence allow either to maximize reasonable disorder detection or to limit expected false positives to 5%. ESpritz performs consistently well on the recent CASP9 data, reaching a S w measure of 54.82 and area under the receiver operator curve of 0.856. The fast predictor is four orders of magnitude faster and remains better than most publicly available CASP9 methods, making it ideal for genomic scale predictions. Conclusions: ESpritz predicts three flavors of disorder at two distinct false positive rates, either with a fast or slower and slightly more accurate approach. Given its state-of-the-art performance, it can be especially useful for high-throughput applications. Availability: Both a web server for high-throughput analysis and a Linux executable version of ESpritz are available from: http://protein.bio.unipd.it/espritz/ Contact: silvio.tosatto@unipd.it Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Clustering protein structures is an important task in structural bioinformatics. De novo structure prediction, for example, often involves a clustering step for finding the best prediction. Other applications include assigning proteins to fold families and analyzing molecular dynamics trajectories. Results: We present Pleiades, a novel approach to clustering protein structures with a rigorous mathematical underpinning. The method approximates clustering based on the root mean square deviation by first mapping structures to Gauss integral vectors—which were introduced by Røgen and co-workers—and subsequently performing K-means clustering. Conclusions: Compared to current methods, Pleiades dramatically improves on the time needed to perform clustering, and can cluster a significantly larger number of structures, while providing state-of-the-art results. The number of low energy structures generated in a typical folding study, which is in the order of 50 000 structures, can be clustered within seconds to minutes. Contact: thamelry@binf.ku.dk ; harder@binf.ku.dk Supplementary Information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Transmembrane β barrel proteins (TMBs) are found in the outer membrane of Gram-negative bacteria, chloroplast and mitochondria. They play a major role in the translocation machinery, pore formation, membrane anchoring and ion exchange. TMBs are also promising targets for antimicrobial drugs and vaccines. Given the difficulty in membrane protein structure determination, computational methods to identify TMBs and predict the topology of TMBs are important. Results: Here, we present BOCTOPUS; an improved method for the topology prediction of TMBs by employing a combination of support vector machines (SVMs) and Hidden Markov Models (HMMs). The SVMs and HMMs account for local and global residue preferences, respectively. Based on a 10-fold cross-validation test, BOCTOPUS performs better than all existing methods, reaching a Q3 accuracy of 87%. Further, BOCTOPUS predicted the correct number of strands for 83% proteins in the dataset. BOCTOPUS might also help in reliable identification of TMBs by using it as an additional filter to methods specialized in this task. Availability: BOCTOPUS is freely available as a web server at: http://boctopus.cbr.su.se/ . The datasets used for training and evaluations are also available from this site. Contact: arne@bioinfo.se Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: High-dimensional data such as microarrays have created new challenges to traditional statistical methods. One such example is on class prediction with high-dimension, low-sample size data. Due to the small sample size, the sample mean estimates are usually unreliable. As a consequence, the performance of the class prediction methods using the sample mean may also be unsatisfactory. To obtain more accurate estimation of parameters some statistical methods, such as regularizations through shrinkage, are often desired. Results: In this article, we investigate the family of shrinkage estimators for the mean value under the quadratic loss function. The optimal shrinkage parameter is proposed under the scenario when the sample size is fixed and the dimension is large. We then construct a shrinkage-based diagonal discriminant rule by replacing the sample mean by the proposed shrinkage mean. Finally, we demonstrate via simulation studies and real data analysis that the proposed shrinkage-based rule outperforms its original competitor in a wide range of settings. Contact: tongt@hkbu.edu.hk

Description: Motivation: The advent of high-throughput sequencing technologies is revolutionizing our ability in discovering and genotyping DNA copy number variants (CNVs). Read count-based approaches are able to detect CNV regions with an unprecedented resolution. Although this computational strategy has been recently introduced in literature, much work has been already done for the preparation, normalization and analysis of this kind of data. Results: Here we face the many aspects that cover the detection of CNVs by using read count approach. We first study the characteristics and systematic biases of read count distributions, focusing on the normalization methods designed for removing these biases. Subsequently, we compare the algorithms designed to detect the boundaries of CNVs and we investigate the ability of read count data to predict the exact number of DNA copy. Finally, we review the tools publicly available for analysing read count data. To better understand the state of the art of read count approaches, we compare the performance of the three most widely used sequencing technologies (Illumina Genome Analyzer, Roche 454 and Life Technologies SOLiD) in all the analyses that we perform. Contact: albertomagi@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: We investigate and quantify the generalizability of the white blood cell (WBC) transcriptome to the general, multiorgan transcriptome. We use data from the NCBI's Gene Expression Omnibus (GEO) public repository to define two datasets for comparison, WBC and OO (Other Organ) sets. Results: Comprehensive pair-wise correlation and expression level profiles are calculated for both datasets (with sizes of 81 and 1463, respectively). We have used mapping and ranking across the Gene Ontology (GO) categories to quantify similarity between the two sets. GO mappings of the most correlated and highly expressed genes from the two datasets tightly match, with the notable exceptions of components of the ribosome, cell adhesion and immune response. That is, 10 877 or 48.8% of all measured genes do not change 〉10% of rank range between WBC and OO; only 878 (3.9%) change rank 〉50%. Two trans -tissue gene lists are defined, the most changing and the least changing genes in expression rank. We also provide a general, quantitative measure of the probability of expression rank and correlation profile in the OO system given the expression rank and correlation profile in the WBC dataset. Contact: vvaltchinov@partners.org Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: The understanding of the molecular sources for diseases like cancer can be significantly improved by computational models. Recently, Boolean networks have become very popular for modeling signaling and regulatory networks. However, such models rely on a set of Boolean functions that are in general not known. Unfortunately, while detailed information on the molecular interactions becomes available in large scale through electronic databases, the information on the Boolean functions does not become available simultaneously and has to be included manually into the models, if at all known. Results: We propose a new Boolean approach which can directly utilize the mechanistic network information available through modern databases. The Boolean function is implicitly defined by the reaction mechanisms. Special care has been taken for the treatment of kinetic features like inhibition. The method has been applied to a signaling model combining the Wnt and MAPK pathway. Availability: A sample C++ implementation of the proposed method is available for Linux and compatible systems through http://code.google.com/p/libscopes/wiki/Paper2011 Contact: handorf@physik.hu-berlin.de Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Multiple sequence alignment (MSA) is a core method in bioinformatics. The accuracy of such alignments may influence the success of downstream analyses such as phylogenetic inference, protein structure prediction, and functional prediction. The importance of MSA has lead to the proliferation of MSA methods, with different objective functions and heuristics to search for the optimal MSA. Different methods of inferring MSAs produce different results in all but the most trivial cases. By measuring the differences between inferred alignments, we may be able to develop an understanding of how these differences (i) relate to the objective functions and heuristics used in MSA methods, and (ii) affect downstream analyses. Results: We introduce four metrics to compare MSAs, which include the position in a sequence where a gap occurs or the location on a phylogenetic tree where an insertion or deletion (indel) event occurs. We use both real and synthetic data to explore the information given by these metrics and demonstrate how the different metrics in combination can yield more information about MSA methods and the differences between them. Availability: MetAl is a free software implementation of these metrics in Haskell. Source and binaries for Windows, Linux and Mac OS X are available from http://kumiho.smith.man.ac.uk/whelan/software/metal/ . Contact: simon.whelan@manchester.ac.uk

Description: Motivation: Peptide detection is a crucial step in mass spectrometry (MS) based proteomics. Most existing algorithms are based upon greedy isotope template matching and thus may be prone to error propagation and ineffective to detect overlapping peptides. In addition, existing algorithms usually work at different charge states separately, isolating useful information that can be drawn from other charge states, which may lead to poor detection of low abundance peptides. Results: BPDA2d models spectra as a mixture of candidate peptide signals and systematically evaluates all possible combinations of possible peptide candidates to interpret the given spectra. For each candidate, BPDA2d takes into account its elution profile, charge state distribution and isotope pattern, and it combines all evidence to infer the candidate's signal and existence probability. By piecing all evidence together—especially by deriving information across charge states—low abundance peptides can be better identified and peptide detection rates can be improved. Instead of local template matching, BPDA2d performs global optimization for all candidates and systematically optimizes their signals. Since BPDA2d looks for the optimal among all possible interpretations of the given spectra, it has the capability in handling complex spectra where features overlap. BPDA2d estimates the posterior existence probability of detected peptides, which can be directly used for probability-based evaluation in subsequent processing steps. Our experiments indicate that BPDA2d outperforms state-of-the-art detection methods on both simulated data and real liquid chromatography–mass spectrometry data, according to sensitivity and detection accuracy. Availability: The BPDA2d software package is available at http://gsp.tamu.edu/Publications/supplementary/sun11a/ Contact: Michelle.Zhang@utsa.edu ; edward@ece.tamu.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: The continued progress in developing technological platforms, availability of many published experimental datasets, as well as different statistical methods to analyze those data have allowed approaching the same research question using various methods simultaneously. To get the best out of all these alternatives, we need to integrate their results in an unbiased manner. Prioritized gene lists are a common result presentation method in genomic data analysis applications. Thus, the rank aggregation methods can become a useful and general solution for the integration task. Results: Standard rank aggregation methods are often ill-suited for biological settings where the gene lists are inherently noisy. As a remedy, we propose a novel robust rank aggregation (RRA) method. Our method detects genes that are ranked consistently better than expected under null hypothesis of uncorrelated inputs and assigns a significance score for each gene. The underlying probabilistic model makes the algorithm parameter free and robust to outliers, noise and errors. Significance scores also provide a rigorous way to keep only the statistically relevant genes in the final list. These properties make our approach robust and compelling for many settings. Availability: All the methods are implemented as a GNU R package R obust R ank A ggreg , freely available at the Comprehensive R Archive Network http://cran.r-project.org/ . Contact: vilo@ut.ee Supplementary information Supplementary data are available at Bioinformatics online.

Description: : CLARE is a computational method designed to reveal sequence encryption of tissue-specific regulatory elements. Starting with a set of regulatory elements known to be active in a particular tissue/process, it learns the sequence code of the input set and builds a predictive model from features specific to those elements. The resulting model can then be applied to user-supplied genomic regions to identify novel candidate regulatory elements. CLARE's model also provides a detailed analysis of transcription factors that most likely bind to the elements, making it an invaluable tool for understanding mechanisms of tissue-specific gene regulation. Availability: CLARE is freely accessible at http://clare.dcode.org/ . Contact: taherl@ncbi.nlm.nih.gov ; ovcharen@nih.gov Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: We present a pipeline for the pre-processing, quality assessment, read distribution and methylation estimation for methylated DNA immunoprecipitation (MeDIP)-sequence datasets. This is the first MeDIP-seq-specific analytic pipeline that starts at the output of the sequencers. This pipeline will reduce the data analysis load on staff and allows the easy and straightforward analysis of sequencing data for DNA methylation. The pipeline integrates customized scripting and several existing tools, which can deal with both paired and single end data. Availability: The package and extensive documentation, and comparison to public data is available at http://life.tongji.edu.cn/meqa/ Contact: jhuang@cephb.fr

Description: Motivation: A plethora of bioinformatics analysis has led to the discovery of numerous gene sets, which can be interpreted as discrete measurements emitted from latent signaling pathways. Their potential to infer signaling pathway structures, however, has not been sufficiently exploited. Existing methods accommodating discrete data do not explicitly consider signal cascading mechanisms that characterize a signaling pathway. Novel computational methods are thus needed to fully utilize gene sets and broaden the scope from focusing only on pairwise interactions to the more general cascading events in the inference of signaling pathway structures. Results: We propose a gene set based simulated annealing (SA) algorithm for the reconstruction of signaling pathway structures. A signaling pathway structure is a directed graph containing up to a few hundred nodes and many overlapping signal cascades, where each cascade represents a chain of molecular interactions from the cell surface to the nucleus. Gene sets in our context refer to discrete sets of genes participating in signal cascades, the basic building blocks of a signaling pathway, with no prior information about gene orderings in the cascades. From a compendium of gene sets related to a pathway, SA aims to search for signal cascades that characterize the optimal signaling pathway structure. In the search process, the extent of overlap among signal cascades is used to measure the optimality of a structure. Throughout, we treat gene sets as random samples from a first-order Markov chain model. We evaluated the performance of SA in three case studies. In the first study conducted on 83 KEGG pathways, SA demonstrated a significantly better performance than Bayesian network methods. Since both SA and Bayesian network methods accommodate discrete data, use a ‘search and score’ network learning strategy and output a directed network, they can be compared in terms of performance and computational time. In the second study, we compared SA and Bayesian network methods using four benchmark datasets from DREAM. In our final study, we showcased two context-specific signaling pathways activated in breast cancer. Availibility: Source codes are available from http://dl.dropbox.com/u/16000775/sa_sc.zip Contact: dzhu@wayne.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : We provide a Bioconductor package with quality assessment, processing and visualization tools for high-throughput sequencing data, with emphasis in ChIP-seq and RNA-seq studies. It includes detection of outliers and biases, inefficient immuno-precipitation and overamplification artifacts, de novo identification of read-rich genomic regions and visualization of the location and coverage of genomic region lists. Availability: www.bioconductor.org Contact: david.rossell@irbbarcelona.org Supplementary information: Supplementary data available at Bioinformatics online.

Description: Motivation: We study a stochastic method for approximating the set of local minima in partial RNA folding landscapes associated with a bounded-distance neighbourhood of folding conformations. The conformations are limited to RNA secondary structures without pseudoknots. The method aims at exploring partial energy landscapes p L induced by folding simulations and their underlying neighbourhood relations. It combines an approximation of the number of local optima devised by Garnier and Kallel (2002) with a run-time estimation for identifying sets of local optima established by Reeves and Eremeev (2004). Results: The method is tested on nine sequences of length between 50 nt and 400 nt, which allows us to compare the results with data generated by RNAsubopt and subsequent barrier tree calculations. On the nine sequences, the method captures on average 92% of local minima with settings designed for a target of 95%. The run-time of the heuristic can be estimated by O ( n 2 D ln), where n is the sequence length, is the number of local minima in the partial landscape p L under consideration and D is the maximum number of steepest descent steps in attraction basins associated with p L . Contact: a.albrecht@qub.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: RNA-seq is a powerful technology for the study of transcriptome profiles that uses deep-sequencing technologies. Moreover, it may be used for cellular phenotyping and help establishing the etiology of diseases characterized by abnormal splicing patterns. In RNA-Seq, the exact nature of splicing events is buried in the reads that span exon–exon boundaries. The accurate and efficient mapping of these reads to the reference genome is a major challenge. Results: We developed PASSion, a pattern growth algorithm-based pipeline for splice site detection in paired-end RNA-Seq reads. Comparing the performance of PASSion to three existing RNA-Seq analysis pipelines, TopHat, MapSplice and HMMSplicer, revealed that PASSion is competitive with these packages. Moreover, the performance of PASSion is not affected by read length and coverage. It performs better than the other three approaches when detecting junctions in highly abundant transcripts. PASSion has the ability to detect junctions that do not have known splicing motifs, which cannot be found by the other tools. Of the two public RNA-Seq datasets, PASSion predicted ~ 137 000 and 173 000 splicing events, of which on average 82 are known junctions annotated in the Ensembl transcript database and 18% are novel. In addition, our package can discover differential and shared splicing patterns among multiple samples. Availability: The code and utilities can be freely downloaded from https://trac.nbic.nl/passion and ftp://ftp.sanger.ac.uk/pub/zn1/passion Contact: y.zhang@lumc.nl ; k.ye@lumc.nl Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: The completion of 168 genome sequences from a single population of Drosophila melanogaster provides a global view of genomic variation and an understanding of the evolutionary forces shaping the patterns of DNA polymorphism and divergence along the genome. Results: We present the ‘Population Drosophila Browser’ (PopDrowser), a new genome browser specially designed for the automatic analysis and representation of genetic variation across the D. melanogaster genome sequence. PopDrowser allows estimating and visualizing the values of a number of DNA polymorphism and divergence summary statistics, linkage disequilibrium parameters and several neutrality tests. PopDrowser also allows performing custom analyses on-the-fly using user-selected parameters. Availability: PopDrowser is freely available from http://PopDrowser.uab.cat . Contact: miquel.ramia@uab.cat