GobyWeb: Simplified Management and Analysis of Gene Expression and DNA Methylation Sequencing Data

We present GobyWeb, a web-based system that facilitates the management and analysis of high-throughput sequencing (HTS) projects. The software provides integrated support for a broad set of HTS analyses and offers a simple plugin extension mechanism. Analyses currently supported include quantification of gene expression for messenger and small RNA sequencing, estimation of DNA methylation (i.e., reduced bisulfite sequencing and whole genome methyl-seq), or the detection of pathogens in sequenced data. In contrast to previous analysis pipelines developed for analysis of HTS data, GobyWeb requires significantly less storage space, runs analyses efficiently on a parallel grid, scales gracefully to process tens or hundreds of multi-gigabyte samples, yet can be used effectively by researchers who are comfortable using a web browser. We conducted performance evaluations of the software and found it to either outperform or have similar performance to analysis programs developed for specialized analyses of HTS data. We found that most biologists who took a one-hour GobyWeb training session were readily able to analyze RNA-Seq data with state of the art analysis tools. GobyWeb can be obtained at http://gobyweb.campagnelab.org and is freely available for non-commercial use. GobyWeb plugins are distributed in source code and licensed under the open source LGPL3 license to facilitate code inspection, reuse and independent extensions http://github.com/CampagneLaboratory/gobyweb2-plugins.     

Genomic Target Database (GTD): A database of potential targets in human pathogenic bacteria

A Genomic Target Database (GTD) has been developed having putative genomic drug targets for human bacterial pathogens. The selected pathogens are either drug resistant or vaccines are yet to be developed against them. The drug targets have been identified using subtractive genomics approaches and these are subsequently classified into

1. Drug targets in pathogen specific unique metabolic pathways,
2. Drug targets in host-pathogen common metabolic pathways, and
3. Membrane localized drug targets.

HTML code is used to link each target to its various properties and other available public resources. Essential resources and tools for subtractive genomic analysis, sub-cellular localization, vaccine and drug designing are also mentioned. To the best of authors knowledge, no such database (DB) is presently available that has listed metabolic pathways and membrane specific genomic drug targets based on subtractive genomics. Listed targets in GTD are readily available resource in developing drug and vaccine against the respective pathogen, its subtypes, and other family members. Currently GTD contains 58 drug targets for four pathogens. Shortly, drug targets for six more pathogens will be listed.

Availability

GTD is available at IIOAB website http://www.iioab.webs.com/GTD.htm. It can also be accessed at http://www.iioabdgd.webs.com.GTD is free for academic research and non-commercial use only. Commercial use is strictly prohibited without prior permission from IIOAB.     

Birds do it,bees do it,worms and ciliates do it too: DNA methylation from unexpected corners of the tree of life

Studies describing intricate patterns of DNA methylation in nematode and ciliate are controversial due to the uncertainty of genomic evolutionary conservation of DNA methylation enzymes.See related research articles http://genomebiology.com/2012/13/10/R99 and http://genomebiology.com/2012/13/10/R100     

Predicted Enhanced Human Propensity of Current Avian-Like H1N1 Swine Influenza Virus from China

Influenza A virus (IAV) subtypes against which little or no pre-existing immunity exists in humans represent a serious threat to global public health. Monitoring of IAV in animal hosts is essential for early and rapid detection of potential pandemic IAV strains to prevent their spread. Recently, the increased pandemic potential of the avian-like swine H1N1 IAV A/swine/Guangdong/104/2013 has been suggested. The virus is infectious in humans and the general population seems to lack neutralizing antibodies against this virus. Here we present an in silico analysis that shows a strong human propensity of this swine virus further confirming its pandemic potential. We suggest mutations which would further enhance its human propensity. We also propose conserved antigenic determinants which could serve as a component of a prepandemic vaccine. The bioinformatics tool, which can be used to further monitor the evolution of swine influenza viruses towards a pandemic virus, are described here and are made publically available (http://www.vin.bg.ac.rs/180/tools/iav_mon.php; http://www.biomedprotection.com/iav_mon.php).     

Piphillin: Improved Prediction of Metagenomic Content by Direct Inference from Human Microbiomes

Functional analysis of a clinical microbiome facilitates the elucidation of mechanisms by which microbiome perturbation can cause a phenotypic change in the patient. The direct approach for the analysis of the functional capacity of the microbiome is via shotgun metagenomics. An inexpensive method to estimate the functional capacity of a microbial community is through collecting 16S rRNA gene profiles then indirectly inferring the abundance of functional genes. This inference approach has been implemented in the PICRUSt and Tax4Fun software tools. However, those tools have important limitations since they rely on outdated functional databases and uncertain phylogenetic trees and require very specific data pre-processing protocols. Here we introduce Piphillin, a straightforward algorithm independent of any proposed phylogenetic tree, leveraging contemporary functional databases and not obliged to any singular data pre-processing protocol. When all three inference tools were evaluated against actual shotgun metagenomics, Piphillin was superior in predicting gene composition in human clinical samples compared to both PICRUSt and Tax4Fun (p<0.01 and p<0.001, respectively) and Piphillin’s ability to predict disease associations with specific gene orthologs exhibited a 15% increase in balanced accuracy compared to PICRUSt. From laboratory animal samples, no performance advantage was observed for any one of the tools over the others and for environmental samples all produced unsatisfactory predictions. Our results demonstrate that functional inference using the direct method implemented in Piphillin is preferable for clinical biospecimens. Piphillin is publicly available for academic use at http://secondgenome.com/Piphillin.     

BIOFFORC: Tool development for biological file format conversion

The use of bioinformatics tools require different sequence formats at various instances. Every tool uses specific set of formats for processing. Sequence in one format is often required in another format. Thus, there is a need for sequence format conversion. A number of such tools are available in the public domain. Here, we describe BIOFFORC as a file format converter. The tool is developed with a graphical user interface in PERL.

Availability

http://www.winningpath.com/biofforc/     

A database for human Y chromosome protein data

The human Y chromosome is the sex determining chromosome. The number of proteins associated with this chromosome is 196 and 107 of the 196 proteins have yet not been characterised. Here, we describe the analysis of these 107 proteins by computing various physicochemical properties using sequence and predicted structural data to elucidate molecular function. We present the derived data in the form a form a database made freely available for download, review, refinement and update.

Availability

http://puratham.googlepages.com/ or http://puratham.googlepages.com/ftpconnection     

A Real-Time All-Atom Structural Search Engine for Proteins

Protein designers use a wide variety of software tools for de novo design, yet their repertoire still lacks a fast and interactive all-atom search engine. To solve this, we have built the Suns program: a real-time, atomic search engine integrated into the PyMOL molecular visualization system. Users build atomic-level structural search queries within PyMOL and receive a stream of search results aligned to their query within a few seconds. This instant feedback cycle enables a new “designability”-inspired approach to protein design where the designer searches for and interactively incorporates native-like fragments from proven protein structures. We demonstrate the use of Suns to interactively build protein motifs, tertiary interactions, and to identify scaffolds compatible with hot-spot residues. The official web site and installer are located at http://www.degradolab.org/suns/ and the source code is hosted at https://github.com/godotgildor/Suns (PyMOL plugin, BSD license), https://github.com/Gabriel439/suns-cmd (command line client, BSD license), and https://github.com/Gabriel439/suns-search (search engine server, GPLv2 license).

This is a PLOS Computational Biology Software Article

     

Bringing non-human primate research into the post-genomic era: how monkeys are teaching us about elite controllers of HIV/AIDS

Whole-genome sequencing of Mauritian cynomolgus macaques reveals novel candidate loci for controlling simian immunodeficiency virus replication.See related Research, http://genomebiology.com/2014/15/11/478     

PROCAIN: protein profile comparison with assisting information

Detection of remote sequence homology is essential for the accurate inference of protein structure, function and evolution. The most sensitive detection methods involve the comparison of evolutionary patterns reflected in multiple sequence alignments (MSAs) of protein families. We present PROCAIN, a new method for MSA comparison based on the combination of ‘vertical’ MSA context (substitution constraints at individual sequence positions) and ‘horizontal’ context (patterns of residue content at multiple positions). Based on a simple and tractable profile methodology and primitive measures for the similarity of horizontal MSA patterns, the method achieves the quality of homology detection comparable to a more complex advanced method employing hidden Markov models (HMMs) and secondary structure (SS) prediction. Adding SS information further improves PROCAIN performance beyond the capabilities of current state-of-the-art tools. The potential value of the method for structure/function predictions is illustrated by the detection of subtle homology between evolutionary distant yet structurally similar protein domains. ProCAIn, relevant databases and tools can be downloaded from: http://prodata.swmed.edu/procain/download. The web server can be accessed at http://prodata.swmed.edu/procain/procain.php.     

Insecticide resistance comes of age

A new study integrates biochemistry, genetics and structural biology to reveal the mechanism of metabolic resistance in a vector mosquito in unprecedented detail.See related research http://genomebiology.com/2014/15/2/R27     

Timber! Felling the loblolly pine genome

Conventional short read sequences derived from haploid DNA were extended into long super-reads enabling assembly of the massive 22 Gbp loblolly pine, Pinus taeda, genome.See related research http://genomebiology.com/2014/15/3/R59     

Identification of evolutionarily meaningful information within the mammalian RNA editing landscape

A large comparative genomic sequence study has determined the extent of conservation between RNA editing sites within the mammalian evolutionary tree.See related research by Pinto et al., http://genomebiology.com/2014/15/1/R5     

The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes

Whole-genome sequences are now available for many microbial species and clades, however existing whole-genome alignment methods are limited in their ability to perform sequence comparisons of multiple sequences simultaneously. Here we present the Harvest suite of core-genome alignment and visualization tools for the rapid and simultaneous analysis of thousands of intraspecific microbial strains. Harvest includes Parsnp, a fast core-genome multi-aligner, and Gingr, a dynamic visual platform. Together they provide interactive core-genome alignments, variant calls, recombination detection, and phylogenetic trees. Using simulated and real data we demonstrate that our approach exhibits unrivaled speed while maintaining the accuracy of existing methods. The Harvest suite is open-source and freely available from: http://github.com/marbl/harvest.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0524-x) contains supplementary material, which is available to authorized users.     

Binding the boundaries of chromatin domains

A new study proposes an integrated framework to improve our understanding of the multiple functions of insulator elements, and their architectural role in the genome.See related research; http://genomebiology.com/2014/15/6/R82     

Of RNA-binding proteins and their targets: interaction determines expression

Combining the prediction of interactions between mRNAs and RNA-binding proteins with experimental expression profiles uncovers novel regulatory paradigms concerning proliferation and differentiation processes.See related research, http://genomebiology.com/2014/15/1/R13     

Tn-Seq Explorer: A Tool for Analysis of High-Throughput Sequencing Data of Transposon Mutant Libraries

Tn-seq is a high throughput technique for analysis of transposon mutant libraries. Tn-seq Explorer was developed as a convenient and easy-to-use package of tools for exploration of the Tn-seq data. In a typical application, the user will have obtained a collection of sequence reads adjacent to transposon insertions in a reference genome. The reads are first aligned to the reference genome using one of the tools available for this task. Tn-seq Explorer reads the alignment and the gene annotation, and provides the user with a set of tools to investigate the data and identify possibly essential or advantageous genes as those that contain significantly low counts of transposon insertions. Emphasis is placed on providing flexibility in selecting parameters and methodology most appropriate for each particular dataset. Tn-seq Explorer is written in Java as a menu-driven, stand-alone application. It was tested on Windows, Mac OS, and Linux operating systems. The source code is distributed under the terms of GNU General Public License. The program and the source code are available for download at http://www.cmbl.uga.edu/downloads/programs/Tn_seq_Explorer/ and https://github.com/sina-cb/Tn-seqExplorer.     

Rising from the crypt: decreasing DNA methylation during differentiation of the small intestine

The differentiation of intestinal stem cells involves few DNA methylation changes, assayed by bisulfite sequencing, in contrast to other adult somatic stem cell hierarchies.Please see related Research article: http://genomebiology.com/2013/14/5/R50