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MemGen: a general web server for the setup of lipid membrane simulation systems

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: Molecular dynamics simulations provide atomic insight into the physicochemical characteristics of lipid membranes and hence, a wide range of force field families capable of modelling various lipid types have been developed in recent years. To model membranes in a biologically realistic lipid composition, simulation systems containing multiple different lipids must be assembled.

Results: We present a new web service called MemGen that is capable of setting up simulation systems of heterogenous lipid membranes. MemGen is not restricted to certain lipid force fields or lipid types, but instead builds membranes from uploaded structure files which may contain any kind of amphiphilic molecule. MemGen works with any all-atom or united-atom lipid representation.

Availability and implementation: MemGen is freely available without registration at http://memgen.uni-goettingen.de.

Contact: jhub@gwdg.de

Supplementary information: Supplementary data are available at Bioinformatics online.

Categories: Journal Articles

chipPCR: an R package to pre-process raw data of amplification curves

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: Both the quantitative real-time polymerase chain reaction (qPCR) and quantitative isothermal amplification (qIA) are standard methods for nucleic acid quantification. Numerous real-time read-out technologies have been developed. Despite the continuous interest in amplification-based techniques, there are only few tools for pre-processing of amplification data. However, a transparent tool for precise control of raw data is indispensable in several scenarios, for example, during the development of new instruments.

Results: chipPCR is an R package for the pre-processing and quality analysis of raw data of amplification curves. The package takes advantage of R’s S4 object model and offers an extensible environment. chipPCR contains tools for raw data exploration: normalization, baselining, imputation of missing values, a powerful wrapper for amplification curve smoothing and a function to detect the start and end of an amplification curve. The capabilities of the software are enhanced by the implementation of algorithms unavailable in R, such as a 5-point stencil for derivative interpolation. Simulation tools, statistical tests, plots for data quality management, amplification efficiency/quantification cycle calculation, and datasets from qPCR and qIA experiments are part of the package. Core functionalities are integrated in GUIs (web-based and standalone shiny applications), thus streamlining analysis and report generation.

Availability and implementation: http://cran.r-project.org/web/packages/chipPCR. Source code: https://github.com/michbur/chipPCR.

Contact: stefan.roediger@b-tu.de

Supplementary information: Supplementary data are available at Bioinformatics online.

Categories: Journal Articles

ms-data-core-api: an open-source, metadata-oriented library for computational proteomics

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Summary: The ms-data-core-api is a free, open-source library for developing computational proteomics tools and pipelines. The Application Programming Interface, written in Java, enables rapid tool creation by providing a robust, pluggable programming interface and common data model. The data model is based on controlled vocabularies/ontologies and captures the whole range of data types included in common proteomics experimental workflows, going from spectra to peptide/protein identifications to quantitative results. The library contains readers for three of the most used Proteomics Standards Initiative standard file formats: mzML, mzIdentML, and mzTab. In addition to mzML, it also supports other common mass spectra data formats: dta, ms2, mgf, pkl, apl (text-based), mzXML and mzData (XML-based). Also, it can be used to read PRIDE XML, the original format used by the PRIDE database, one of the world-leading proteomics resources. Finally, we present a set of algorithms and tools whose implementation illustrates the simplicity of developing applications using the library.

Availability and implementation: The software is freely available at https://github.com/PRIDE-Utilities/ms-data-core-api.

Supplementary information: Supplementary data are available at Bioinformatics online

Contact: juan@ebi.ac.uk

Categories: Journal Articles

Gener: a minimal programming module for chemical controllers based on DNA strand displacement

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Summary: Gener is a development module for programming chemical controllers based on DNA strand displacement. Gener is developed with the aim of providing a simple interface that minimizes the opportunities for programming errors: Gener allows the user to test the computations of the DNA programs based on a simple two-domain strand displacement algebra, the minimal available so far. The tool allows the user to perform stepwise computations with respect to the rules of the algebra as well as exhaustive search of the computation space with different options for exploration and visualization. Gener can be used in combination with existing tools, and in particular, its programs can be exported to Microsoft Research’s DSD tool as well as to LaTeX.

Availability and implementation: Gener is available for download at the Cosbi website at http://www.cosbi.eu/research/prototypes/gener as a windows executable that can be run on Mac OS X and Linux by using Mono.

Contact: ozan@cosbi.eu

Categories: Journal Articles

phylogeo: an R package for geographic analysis and visualization of microbiome data

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: We have created an R package named phylogeo that provides a set of geographic utilities for sequencing-based microbial ecology studies. Although the geographic location of samples is an important aspect of environmental microbiology, none of the major software packages used in processing microbiome data include utilities that allow users to map and explore the spatial dimension of their data. phylogeo solves this problem by providing a set of plotting and mapping functions that can be used to visualize the geographic distribution of samples, to look at the relatedness of microbiomes using ecological distance, and to map the geographic distribution of particular sequences. By extending the popular phyloseq package and using the same data structures and command formats, phylogeo allows users to easily map and explore the geographic dimensions of their data from the R programming language.

Availability and Implementation: phylogeo is documented and freely available http://zachcp.github.io/phylogeo

Contact: zcharlop@rockefeller.edu

Categories: Journal Articles

GOplot: an R package for visually combining expression data with functional analysis

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Summary: Despite the plethora of methods available for the functional analysis of omics data, obtaining comprehensive-yet detailed understanding of the results remains challenging. This is mainly due to the lack of publicly available tools for the visualization of this type of information. Here we present an R package called GOplot, based on ggplot2, for enhanced graphical representation. Our package takes the output of any general enrichment analysis and generates plots at different levels of detail: from a general overview to identify the most enriched categories (bar plot, bubble plot) to a more detailed view displaying different types of information for molecules in a given set of categories (circle plot, chord plot, cluster plot). The package provides a deeper insight into omics data and allows scientists to generate insightful plots with only a few lines of code to easily communicate the findings.

Availability and Implementation: The R package GOplot is available via CRAN-The Comprehensive R Archive Network: http://cran.r-project.org/web/packages/GOplot. The shiny web application of the Venn diagram can be found at: https://wwalter.shinyapps.io/Venn/. A detailed manual of the package with sample figures can be found at https://wencke.github.io/

Contact: fscabo@cnic.es or mricote@cnic.es

Categories: Journal Articles

HTT-DB: Horizontally transferred transposable elements database

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: Horizontal transfer of transposable (HTT) elements among eukaryotes was discovered in the mid-1980s. As then, >300 new cases have been described. New findings about HTT are revealing the evolutionary impact of this phenomenon on host genomes. In order to provide an up to date, interactive and expandable database for such events, we developed the HTT-DB database.

Results: HTT-DB allows easy access to most of HTT cases reported along with rich information about each case. Moreover, it allows the user to generate tables and graphs based on searches using Transposable elements and/or host species classification and export them in several formats.

Availability and implementation: This database is freely available on the web at http://lpa.saogabriel.unipampa.edu.br:8080/httdatabase. HTT-DB was developed based on Java and MySQL with all major browsers supported. Tools and software packages used are free for personal or non-profit projects.

Contact: bdotto82@gmail.com or gabriel.wallau@gmail.com

Categories: Journal Articles

'Flatten plus': a recent implementation in WSxM for biological research

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Summary: Scanning probe microscopy (SPM) is already a relevant tool in biological research at the nanoscale. We present ‘Flatten plus’, a recent and helpful implementation in the well-known WSxM free software package. ‘Flatten plus’ allows reducing low-frequency noise in SPM images in a semi-automated way preventing the appearance of typical artifacts associated with such filters.

Availability and implementation: WSxM is a free software implemented in C++ supported on MS Windows, but it can also be run under Mac or Linux using emulators such as Wine or Parallels. WSxM can be downloaded from http://www.wsxmsolutions.com/.

Contact: ignacio.horcas@wsxmsolutions.com

Categories: Journal Articles

Predicting effects of noncoding variants with deep learning–based sequence model

Nature Methods - Sun, 08/23/2015 - 23:00

Nature Methods 12, 931 (2015). doi:10.1038/nmeth.3547

Authors: Jian Zhou & Olga G Troyanskaya

Identifying functional effects of noncoding variants is a major challenge in human genetics. To predict the noncoding-variant effects de novo from sequence, we developed a deep learning–based algorithmic framework, DeepSEA (http://deepsea.princeton.edu/), that directly learns a regulatory sequence code from large-scale chromatin-profiling data, enabling prediction of chromatin effects of sequence alterations with single-nucleotide sensitivity. We further used this capability to improve prioritization of functional variants including expression quantitative trait loci (eQTLs) and disease-associated variants.

Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq experiments

Nature Methods - Sun, 08/23/2015 - 23:00

Nature Methods 12, 947 (2015). doi:10.1038/nmeth.3549

Authors: Ning Leng, Li-Fang Chu, Chris Barry, Yuan Li, Jeea Choi, Xiaomao Li, Peng Jiang, Ron M Stewart, James A Thomson & Christina Kendziorski

Oscillatory gene expression is fundamental to development, but technologies for monitoring expression oscillations are limited. We have developed a statistical approach called Oscope to identify and characterize the transcriptional dynamics of oscillating genes in single-cell RNA-seq data from an unsynchronized cell population. Applying Oscope to a number of data sets, we demonstrated its utility and also identified a potential artifact in the Fluidigm C1 platform.

Trajectories of cell-cycle progression from fixed cell populations

Nature Methods - Sun, 08/23/2015 - 23:00

Nature Methods 12, 951 (2015). doi:10.1038/nmeth.3545

Authors: Gabriele Gut, Michelle D Tadmor, Dana Pe'er, Lucas Pelkmans & Prisca Liberali

An accurate dissection of sources of cell-to-cell variability is crucial for quantitative biology at the single-cell level but has been challenging for the cell cycle. We present Cycler, a robust method that constructs a continuous trajectory of cell-cycle progression from images of fixed cells. Cycler handles heterogeneous microenvironments and does not require perturbations or genetic markers, making it generally applicable to quantifying multiple sources of cell-to-cell variability in mammalian cells.

Hurricane Katrina’s psychological scars revealed

Nature - Sun, 08/23/2015 - 23:00

Hurricane Katrina’s psychological scars revealed

Nature 524, 7566 (2015). http://www.nature.com/doifinder/10.1038/524395a

Author: Sara Reardon

Mental health worsened in the disaster’s aftermath, but survivors also showed resilience.

Categories: Journal Articles

Changes in Postural Syntax Characterize Sensory Modulation and Natural Variation of C. elegans Locomotion

PLoS Computational Biology - Fri, 08/21/2015 - 16:00

by Roland F. Schwarz, Robyn Branicky, Laura J. Grundy, William R. Schafer, André E. X. Brown

Locomotion is driven by shape changes coordinated by the nervous system through time; thus, enumerating an animal's complete repertoire of shape transitions would provide a basis for a comprehensive understanding of locomotor behaviour. Here we introduce a discrete representation of behaviour in the nematode C. elegans. At each point in time, the worm’s posture is approximated by its closest matching template from a set of 90 postures and locomotion is represented as sequences of postures. The frequency distribution of postural sequences is heavy-tailed with a core of frequent behaviours and a much larger set of rarely used behaviours. Responses to optogenetic and environmental stimuli can be quantified as changes in postural syntax: worms show different preferences for different sequences of postures drawn from the same set of templates. A discrete representation of behaviour will enable the use of methods developed for other kinds of discrete data in bioinformatics and language processing to be harnessed for the study of behaviour.
Categories: Journal Articles

Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces

PLoS Computational Biology - Fri, 08/21/2015 - 16:00

by Cahit Dalgicdir, Christoph Globisch, Christine Peter, Mehmet Sayar

Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK) and EAALAEALAEALAE (EALA), with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides’ response to macroscopic and molecular interfaces (presented by an aggregation partner) can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides’ aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity.
Categories: Journal Articles

Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation

PLoS Computational Biology - Fri, 08/21/2015 - 16:00

by James P. Roach, Eshel Ben-Jacob, Leonard M. Sander, Michal R. Zochowski

Acetylcholine (ACh) is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA) and a shift in the phase response curve (PRC). We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS) differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh) patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh), traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.
Categories: Journal Articles

Correction: Time-Course Gene Set Analysis for Longitudinal Gene Expression Data

PLoS Computational Biology - Fri, 08/21/2015 - 16:00

by The PLOS Computational Biology Staff

Categories: Journal Articles

Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses

PLoS Computational Biology - Thu, 08/20/2015 - 16:00

by Gabriel Koch Ocker, Ashok Litwin-Kumar, Brent Doiron

The synaptic connectivity of cortical networks features an overrepresentation of certain wiring motifs compared to simple random-network models. This structure is shaped, in part, by synaptic plasticity that promotes or suppresses connections between neurons depending on their joint spiking activity. Frequently, theoretical studies focus on how feedforward inputs drive plasticity to create this network structure. We study the complementary scenario of self-organized structure in a recurrent network, with spike timing-dependent plasticity driven by spontaneous dynamics. We develop a self-consistent theory for the evolution of network structure by combining fast spiking covariance with a slow evolution of synaptic weights. Through a finite-size expansion of network dynamics we obtain a low-dimensional set of nonlinear differential equations for the evolution of two-synapse connectivity motifs. With this theory in hand, we explore how the form of the plasticity rule drives the evolution of microcircuits in cortical networks. When potentiation and depression are in approximate balance, synaptic dynamics depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian STDP these motif interactions create instabilities in synaptic dynamics that either promote or suppress the initial network structure. Our work provides a consistent theoretical framework for studying how spiking activity in recurrent networks interacts with synaptic plasticity to determine network structure.
Categories: Journal Articles

Experimentally Verified Parameter Sets for Modelling Heterogeneous Neocortical Pyramidal-Cell Populations

PLoS Computational Biology - Thu, 08/20/2015 - 16:00

by Paul M. Harrison, Laurent Badel, Mark J. Wall, Magnus J. E. Richardson

Models of neocortical networks are increasingly including the diversity of excitatory and inhibitory neuronal classes. Significant variability in cellular properties are also seen within a nominal neuronal class and this heterogeneity can be expected to influence the population response and information processing in networks. Recent studies have examined the population and network effects of variability in a particular neuronal parameter with some plausibly chosen distribution. However, the empirical variability and covariance seen across multiple parameters are rarely included, partly due to the lack of data on parameter correlations in forms convenient for model construction. To addess this we quantify the heterogeneity within and between the neocortical pyramidal-cell classes in layers 2/3, 4, and the slender-tufted and thick-tufted pyramidal cells of layer 5 using a combination of intracellular recordings, single-neuron modelling and statistical analyses. From the response to both square-pulse and naturalistic fluctuating stimuli, we examined the class-dependent variance and covariance of electrophysiological parameters and identify the role of the h current in generating parameter correlations. A byproduct of the dynamic I-V method we employed is the straightforward extraction of reduced neuron models from experiment. Empirically these models took the refractory exponential integrate-and-fire form and provide an accurate fit to the perisomatic voltage responses of the diverse pyramidal-cell populations when the class-dependent statistics of the model parameters were respected. By quantifying the parameter statistics we obtained an algorithm which generates populations of model neurons, for each of the four pyramidal-cell classes, that adhere to experimentally observed marginal distributions and parameter correlations. As well as providing this tool, which we hope will be of use for exploring the effects of heterogeneity in neocortical networks, we also provide the code for the dynamic I-V method and make the full electrophysiological data set available.
Categories: Journal Articles

Computational scheme for pH-dependent binding free energy calculation with explicit solvent

Protein Science - Thu, 08/20/2015 - 13:17
Abstract

We present a computational scheme to compute the pH-dependence of binding free energy with explicit solvent. Despite the importance of pH, the effect of pH has been generally neglected in binding free energy calculations because of a lack of accurate methods to model it. To address this limitation, we use a constant-pH methodology to obtain a true ensemble of multiple protonation states of a titratable system at a given pH and analyze the ensemble using the Bennett acceptance ratio (BAR) method. The constant pH method is based on the combination of enveloping distribution sampling (EDS) with the Hamiltonian replica exchange method (HREM), which yields an accurate semi-grand canonical ensemble of a titratable system. By considering the free energy change of constraining multiple protonation states to a single state or releasing a single protonation state to multiple states, the pH dependent binding free energy profile can be obtained. We perform benchmark simulations of a host-guest system: cucurbit[7]uril (CB[7]) and benzimidazole (BZ). BZ experiences a large pKa shift upon complex formation. The pH-dependent binding free energy profiles of the benchmark system are obtained with three different long-range interaction calculation schemes: a cutoff, the particle mesh Ewald (PME), and the isotropic periodic sum (IPS) method. Our scheme captures the pH-dependent behavior of binding free energy successfully. Absolute binding free energy values obtained with the PME and IPS methods are consistent, while cutoff method results are off by 2 kcal mol−1. We also discuss the characteristics of three long-range interaction calculation methods for constant-pH simulations.

Categories: Journal Articles

North Pacific ‘blob’ stirs up fisheries management

Nature - Wed, 08/19/2015 - 23:00

North Pacific ‘blob’ stirs up fisheries management

Nature 524, 7566 (2015). http://www.nature.com/doifinder/10.1038/nature.2015.18218

Author: Virginia Gewin

Unusually warm ocean strengthens calls to consider ecosystem variables in setting catch limits.

Categories: Journal Articles
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