SCUDO: a tool for signature-based clustering of expression profiles

角:基于工具的签名表达谱聚类

SCUDO (Signature-based ClUstering for DiagnOstic purposes) is an online tool for the analysis of gene expression profiles for diagnostic and classification purposes. The tool is based on a new method for the clustering of profiles based on a subject-specific, as opposed to disease-specific, signature. Our approach relies on construction of a reference map of transcriptional signatures, from both healthy and affected subjects, derived from their respective mRNA or miRNA profiles. A diagnosis for a new individual can then be performed by determining the position of the individual's transcriptional signature on the map. The diagnostic power of our method has been convincingly demonstrated in an open scientific competition (SBV Improver Diagnostic Signature Challenge), scoring second place overall and first place in one of the sub-challenges.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Web Server Issue

The Confidence Information Ontology: a step towards a standard for asserting confidence in annotations

信心:对信息本体的断言信心注释的标准步骤

Biocuration has become a cornerstone for analyses in biology, and to meet needs, the amount of annotations has considerably grown in recent years. However, the reliability of these annotations varies; it has thus become necessary to be able to assess the confidence in annotations. Although several resources already provide confidence information about the annotations that they produce, a standard way of providing such information has yet to be defined. This lack of standardization undermines the propagation of knowledge across resources, as well as the credibility of results from high-throughput analyses. Seeded at a workshop during the Biocuration 2012 conference, a working group has been created to address this problem. We present here the elements that were identified as essential for assessing confidence in annotations, as well as a draft ontology—the Confidence Information Ontology—to illustrate how the problems identified could be addressed. We hope that this effort will provide a home for discussing this major issue among the biocuration community.

Tracker URL: https://github.com/BgeeDB/confidence-information-ontology

Ontology URL: https://raw.githubusercontent.com/BgeeDB/confidence-information-ontology/master/src/ontology/cio-simple.obo

[详细]

  • Database
  • 10年前
  • Original Article

FastMotif: spectral sequence motif discovery

FastMotif:spectral discovery影片顺序

Motivation: Sequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, most of the existing motif finding algorithms are computationally demanding, and they may not be able to support the increasingly large datasets produced by modern high-throughput sequencing technologies.

Results: We present FastMotif, a new motif discovery algorithm that is built on a recent machine learning technique referred to as Method of Moments. Based on spectral decompositions, our method is robust to model misspecifications and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. On HT-Selex data, FastMotif extracts motif profiles that match those computed by various state-of-the-art algorithms, but one order of magnitude faster. We provide a theoretical and numerical analysis of the algorithm’s robustness and discuss its sensitivity with respect to the free parameters.

Availability and implementation: The Matlab code of FastMotif is available from http://lcsb-portal.uni.lu/bioinformatics.

Contact: vlassis@adobe.com

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • ORIGINAL PAPER

Soup to tree: the phylogeny of beetles inferred by mitochondrial metagenomics of a Bornean rainforest sample

汤树:甲虫的婆罗洲雨林样本的线粒体基因组的系统发育推断

In spite of the growth of molecular ecology, systematics and next-generation sequencing, the discovery and analysis of diversity is not currently integrated with building the tree-of-life. Tropical arthropod ecologists are well placed to accelerate this process if all specimens obtained via mass-trapping, many of which will be new species, could be incorporated routinely in phylogeny reconstruction. Here we test a shotgun sequencing approach, whereby mitochondrial genomes are assembled from complex ecological mixtures via mitochondrial metagenomics, and demonstrate how the approach overcomes many of the taxonomic impediments to the study of biodiversity. DNA from ~500 beetle specimens, originating from a single rainforest canopy fogging sample from Borneo, was pooled and shotgun sequenced, followed by de novo assembly of complete and partial mitogenomes for 175 species. The phylogenetic tree obtained from this local sample was highly similar to that from existing mitogenomes selected for global coverage of major lineages of Coleoptera. When all sequences were combined, only minor topological changes are induced against this reference set, indicating an increasingly stable estimate of coleopteran phylogeny, whilst the ecological sample expands the tip-level representation of several lineages. Robust trees generated from ecological samples now enable an evolutionary framework for ecology. Meanwhile, the inclusion of uncharacterized samples in the tree-of-life rapidly expands taxon and biogeographic representation of lineages without morphological identification. Mitogenomes from shotgun sequencing of unsorted environmental samples and their associated metadata, placed robustly into the phylogenetic tree, constitute novel DNA ‘superbarcodes’ for testing hypotheses regarding global patterns of diversity.

[详细]

  • Molecular Biology and Evolution
  • 10年前
  • Article

Versatile genetic assembly system (VEGAS) to assemble pathways for expression in S. cerevisiae

多才多艺的遗传装配系统(拉斯维加斯)组装途径的酿酒酵母中的表达

We have developed a method for assembling genetic pathways for expression in Saccharomyces cerevisiae. Our pathway assembly method, called VEGAS (Versatile genetic assembly system), exploits the native capacity of S. cerevisiae to perform homologous recombination and efficiently join sequences with terminal homology. In the VEGAS workflow, terminal homology between adjacent pathway genes and the assembly vector is encoded by ‘VEGAS adapter’ (VA) sequences, which are orthogonal in sequence with respect to the yeast genome. Prior to pathway assembly by VEGAS in S. cerevisiae, each gene is assigned an appropriate pair of VAs and assembled using a previously described technique called yeast Golden Gate (yGG). Here we describe the application of yGG specifically to building transcription units for VEGAS assembly as well as the VEGAS methodology. We demonstrate the assembly of four-, five- and six-gene pathways by VEGAS to generate S. cerevisiae cells synthesizing β-carotene and violacein. Moreover, we demonstrate the capacity of yGG coupled to VEGAS for combinatorial assembly.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Synthetic Biology and Bioengineering

YeastFab: the design and construction of standard biological parts for metabolic engineering in Saccharomyces cerevisiae

yeastfab:酿酒酵母代谢工程标准生物组件的设计与施工

It is a routine task in metabolic engineering to introduce multicomponent pathways into a heterologous host for production of metabolites. However, this process sometimes may take weeks to months due to the lack of standardized genetic tools. Here, we present a method for the design and construction of biological parts based on the native genes and regulatory elements in Saccharomyces cerevisiae. We have developed highly efficient protocols (termed YeastFab Assembly) to synthesize these genetic elements as standardized biological parts, which can be used to assemble transcriptional units in a single-tube reaction. In addition, standardized characterization assays are developed using reporter constructs to calibrate the function of promoters. Furthermore, the assembled transcription units can be either assayed individually or applied to construct multi-gene metabolic pathways, which targets a genomic locus or a receiving plasmid effectively, through a simple in vitro reaction. Finally, using β-carotene biosynthesis pathway as an example, we demonstrate that our method allows us not only to construct and test a metabolic pathway in several days, but also to optimize the production through combinatorial assembly of a pathway using hundreds of regulatory biological parts.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Methods Online

PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins

pockdrug服务器:新的Web服务器预测成药全息和载脂蛋白的口袋

Predicting protein pocket's ability to bind drug-like molecules with high affinity, i.e. druggability, is of major interest in the target identification phase of drug discovery. Therefore, pocket druggability investigations represent a key step of compound clinical progression projects. Currently computational druggability prediction models are attached to one unique pocket estimation method despite pocket estimation uncertainties. In this paper, we propose ‘PockDrug-Server’ to predict pocket druggability, efficient on both (i) estimated pockets guided by the ligand proximity (extracted by proximity to a ligand from a holo protein structure) and (ii) estimated pockets based solely on protein structure information (based on amino atoms that form the surface of potential binding cavities). PockDrug-Server provides consistent druggability results using different pocket estimation methods. It is robust with respect to pocket boundary and estimation uncertainties, thus efficient using apo pockets that are challenging to estimate. It clearly distinguishes druggable from less druggable pockets using different estimation methods and outperformed recent druggability models for apo pockets. It can be carried out from one or a set of apo/holo proteins using different pocket estimation methods proposed by our web server or from any pocket previously estimated by the user. PockDrug-Server is publicly available at: http://pockdrug.rpbs.univ-paris-diderot.fr.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Web Server Issue

ProtPhylo: identification of protein-phenotype and protein-protein functional associations via phylogenetic profiling

protphylo:通过系统发育分析蛋白质表型和蛋白质功能关联识别

ProtPhylo is a web-based tool to identify proteins that are functionally linked to either a phenotype or a protein of interest based on co-evolution. ProtPhylo infers functional associations by comparing protein phylogenetic profiles (co-occurrence patterns of orthology relationships) for more than 9.7 million non-redundant protein sequences from all three domains of life. Users can query any of 2048 fully sequenced organisms, including 1678 bacteria, 255 eukaryotes and 115 archaea. In addition, they can tailor ProtPhylo to a particular kind of biological question by choosing among four main orthology inference methods based either on pair-wise sequence comparisons (One-way Best Hits and Best Reciprocal Hits) or clustering of orthologous proteins across multiple species (OrthoMCL and eggNOG). Next, ProtPhylo ranks phylogenetic neighbors of query proteins or phenotypic properties using the Hamming distance as a measure of similarity between pairs of phylogenetic profiles. Candidate hits can be easily and flexibly prioritized by complementary clues on subcellular localization, known protein–protein interactions, membrane spanning regions and protein domains. The resulting protein list can be quickly exported into a csv text file for further analyses. ProtPhylo is freely available at http://www.protphylo.org.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Web Server Issue

Assembly constraints drive co-evolution among ribosomal constituents

装配约束驱动的协同进化核糖体成分

Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein–RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein–rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a ‘proof of concept’ that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Computational Biology

Mitochondrial translocation of APE1 relies on the MIA pathway

线粒体易位APE1依赖MIA途径

APE1 is a multifunctional protein with a fundamental role in repairing nuclear and mitochondrial DNA lesions caused by oxidative and alkylating agents. Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular trafficking are still fragmentary and contrasting. Recent data demonstrate that APE1 interacts with the mitochondrial import and assembly protein Mia40 suggesting the involvement of a redox-assisted mechanism, dependent on the disulfide transfer system, to be responsible of APE1 trafficking into the mitochondria. The MIA pathway is an import machinery that uses a redox system for cysteine enriched proteins to drive them in this compartment. It is composed by two main proteins: Mia40 is the oxidoreductase that catalyzes the formation of the disulfide bonds in the substrate, while ALR reoxidizes Mia40 after the import. In this study, we demonstrated that: (i) APE1 and Mia40 interact through disulfide bond formation; and (ii) Mia40 expression levels directly affect APE1's mitochondrial translocation and, consequently, play a role in the maintenance of mitochondrial DNA integrity. In summary, our data strongly support the hypothesis of a redox-assisted mechanism, dependent on Mia40, in controlling APE1 translocation into the mitochondrial inner membrane space and thus highlight the role of this protein transport pathway in the maintenance of mitochondrial DNA stability and cell survival.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Genome integrity, repair and replication

xVis: a web server for the schematic visualization and interpretation of crosslink-derived spatial restraints

xvis:用于可视化和空间限制解释Web服务器导出的交联

The identification of crosslinks by mass spectrometry has recently been established as an integral part of the hybrid structural analysis of protein complexes and networks. The crosslinking analysis determines distance restraints between two covalently linked amino acids which are typically summarized in a table format that precludes the immediate and comprehensive interpretation of the topological data. xVis displays crosslinks in clear schematic representations in form of a circular, bar or network diagram. The interactive graphs indicate the linkage sites and identification scores, depict the spatial proximity of structurally and functionally annotated protein regions and the evolutionary conservation of amino acids and facilitate clustering of proteins into subcomplexes according to the crosslink density. Furthermore, xVis offers two options for the qualitative assessment of the crosslink identifications by filtering crosslinks according to identification scores or false discovery rates and by displaying the corresponding fragment ion spectrum of each crosslink for the manual validation of the mass spectrometric data. Our web server provides an easy-to-use tool for the fast topological and functional interpretation of distance information on protein complex architectures and for the evaluation of crosslink fragment ion spectra. xVis is available under a Creative Commons Attribution-ShareAlike 4.0 International license at http://xvis.genzentrum.lmu.de/.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Web Server Issue

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

件:一个最小的编程模块化学位移控制器基于DNA链

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: 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

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

Assessing allele-specific expression across multiple tissues from RNA-seq read data

评估allele-specific表达式从RNA-seq读数据跨多个组织

Motivation: RNA sequencing enables allele-specific expression (ASE) studies that complement standard genotype expression studies for common variants and, importantly, also allow measuring the regulatory impact of rare variants. The Genotype-Tissue Expression (GTEx) project is collecting RNA-seq data on multiple tissues of a same set of individuals and novel methods are required for the analysis of these data.

Results: We present a statistical method to compare different patterns of ASE across tissues and to classify genetic variants according to their impact on the tissue-wide expression profile. We focus on strong ASE effects that we are expecting to see for protein-truncating variants, but our method can also be adjusted for other types of ASE effects. We illustrate the method with a real data example on a tissue-wide expression profile of a variant causal for lipoid proteinosis, and with a simulation study to assess our method more generally.

Availability and implementation: http://www.well.ox.ac.uk/~rivas/mamba/. R-sources and data examples http://www.iki.fi/mpirinen/

Contact: matti.pirinen@helsinki.fi or rivas@well.ox.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • ORIGINAL PAPER

Addressing false discoveries in network inference

解决错误的发现网络推理

Motivation: Experimentally determined gene regulatory networks can be enriched by computational inference from high-throughput expression profiles. However, the prediction of regulatory interactions is severely impaired by indirect and spurious effects, particularly for eukaryotes. Recently, published methods report improved predictions by exploiting the a priori known targets of a regulator (its local topology) in addition to expression profiles.

Results: We find that methods exploiting known targets show an unexpectedly high rate of false discoveries. This leads to inflated performance estimates and the prediction of an excessive number of new interactions for regulators with many known targets. These issues are hidden from common evaluation and cross-validation setups, which is due to Simpson’s paradox. We suggest a confidence score recalibration method (CoRe) that reduces the false discovery rate and enables a reliable performance estimation.

Conclusions: CoRe considerably improves the results of network inference methods that exploit known targets. Predictions then display the biological process specificity of regulators more correctly and enable the inference of accurate genome-wide regulatory networks in eukaryotes. For yeast, we propose a network with more than 22 000 confident interactions. We point out that machine learning approaches outside of the area of network inference may be affected as well.

Availability and implementation: Results, executable code and networks are available via our website http://www.bio.ifi.lmu.de/forschung/CoRe.

Contact: robert.kueffner@helmholtz-muenchen.de

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • ORIGINAL PAPER

MetaSV: an accurate and integrative structural-variant caller for next generation sequencing

MetaSV:准确、综合structural-variant调用者为下一代测序

Summary: Structural variations (SVs) are large genomic rearrangements that vary significantly in size, making them challenging to detect with the relatively short reads from next-generation sequencing (NGS). Different SV detection methods have been developed; however, each is limited to specific kinds of SVs with varying accuracy and resolution. Previous works have attempted to combine different methods, but they still suffer from poor accuracy particularly for insertions. We propose MetaSV, an integrated SV caller which leverages multiple orthogonal SV signals for high accuracy and resolution. MetaSV proceeds by merging SVs from multiple tools for all types of SVs. It also analyzes soft-clipped reads from alignment to detect insertions accurately since existing tools underestimate insertion SVs. Local assembly in combination with dynamic programming is used to improve breakpoint resolution. Paired-end and coverage information is used to predict SV genotypes. Using simulation and experimental data, we demonstrate the effectiveness of MetaSV across various SV types and sizes.

Availability and implementation: Code in Python is at http://bioinform.github.io/metasv/.

Contact: rd@bina.com

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

Cellular phenotype database: a repository for systems microscopy data

细胞表型数据库:存储库系统显微镜数据

Motivation: The Cellular Phenotype Database (CPD) is a repository for data derived from high-throughput systems microscopy studies. The aims of this resource are: (i) to provide easy access to cellular phenotype and molecular localization data for the broader research community; (ii) to facilitate integration of independent phenotypic studies by means of data aggregation techniques, including use of an ontology and (iii) to facilitate development of analytical methods in this field.

Results: In this article we present CPD, its data structure and user interface, propose a minimal set of information describing RNA interference experiments, and suggest a generic schema for management and aggregation of outputs from phenotypic or molecular localization experiments. The database has a flexible structure for management of data from heterogeneous sources of systems microscopy experimental outputs generated by a variety of protocols and technologies and can be queried by gene, reagent, gene attribute, study keywords, phenotype or ontology terms.

Availability and implementation: CPD is developed as part of the Systems Microscopy Network of Excellence and is accessible at http://www.ebi.ac.uk/fg/sym.

Contact: jes@ebi.ac.uk or ugis@ebi.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • ORIGINAL PAPER

Efficient exploration of pan-cancer networks by generalized covariance selection and interactive web content

通过广义协方差选择和交互式Web内容泛癌症网络的有效探索

Statistical network modeling techniques are increasingly important tools to analyze cancer genomics data. However, current tools and resources are not designed to work across multiple diagnoses and technical platforms, thus limiting their applicability to comprehensive pan-cancer datasets such as The Cancer Genome Atlas (TCGA). To address this, we describe a new data driven modeling method, based on generalized Sparse Inverse Covariance Selection (SICS). The method integrates genetic, epigenetic and transcriptional data from multiple cancers, to define links that are present in multiple cancers, a subset of cancers, or a single cancer. It is shown to be statistically robust and effective at detecting direct pathway links in data from TCGA. To facilitate interpretation of the results, we introduce a publicly accessible tool (cancerlandscapes.org), in which the derived networks are explored as interactive web content, linked to several pathway and pharmacological databases. To evaluate the performance of the method, we constructed a model for eight TCGA cancers, using data from 3900 patients. The model rediscovered known mechanisms and contained interesting predictions. Possible applications include prediction of regulatory relationships, comparison of network modules across multiple forms of cancer and identification of drug targets.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Methods Online

Structure of the nuclease subunit of human mitochondrial RNase P

对人类线粒体RNase P的核酸酶的亚基结构

Mitochondrial RNA polymerase produces long polycistronic precursors that contain the mRNAs, rRNAs and tRNAs needed for mitochondrial translation. Mitochondrial RNase P (mt-RNase P) initiates the maturation of the precursors by cleaving at the 5' ends of the tRNAs. Human mt-RNase P is only active as a tripartite complex (mitochondrial RNase P proteins 1–3; MRPP1-3), whereas plant and trypanosomal RNase Ps (PRORPs)—albeit homologous to MRPP3—are active as single proteins. The reason for this discrepancy has so far remained obscure. Here, we present the crystal structure of human MRPP3, which features a remarkably distorted and hence non-productive active site that we propose will switch to a fully productive state only upon association with MRPP1, MRPP2 and pre-tRNA substrate. We suggest a mechanism in which MRPP1 and MRPP2 both deliver the pre-tRNA substrate and activate MRPP3 through an induced-fit process.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Structural Biology

Human RNase P ribonucleoprotein is required for formation of initiation complexes of RNA polymerase III

人类核糖核酸酶P的RNA聚合酶蛋白是起始复合物形成三要求

Human RNase P is implicated in transcription of small non-coding RNA genes by RNA polymerase III (Pol III), but the precise role of this ribonucleoprotein therein remains unknown. We here show that targeted destruction of HeLa nuclear RNase P inhibits transcription of 5S rRNA genes in whole cell extracts, if this precedes the stage of initiation complex formation. Biochemical purification analyses further reveal that this ribonucleoprotein is recruited to 5S rRNA genes as a part of proficient initiation complexes and the activity persists at reinitiation. Knockdown of RNase P abolishes the assembly of initiation complexes by preventing the formation of the initiation sub-complex of Pol III. Our results demonstrate that the structural intactness, but not the endoribonucleolytic activity per se, of RNase P is critical for the function of Pol III in cells and in extracts.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Gene regulation, Chromatin and Epigenetics

The MEME Suite

MEME套件

The MEME Suite is a powerful, integrated set of web-based tools for studying sequence motifs in proteins, DNA and RNA. Such motifs encode many biological functions, and their detection and characterization is important in the study of molecular interactions in the cell, including the regulation of gene expression. Since the previous description of the MEME Suite in the 2009 Nucleic Acids Research Web Server Issue, we have added six new tools. Here we describe the capabilities of all the tools within the suite, give advice on their best use and provide several case studies to illustrate how to combine the results of various MEME Suite tools for successful motif-based analyses. The MEME Suite is freely available for academic use at http://meme-suite.org, and source code is also available for download and local installation.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Web Server issue

RAX2: a genome-wide detection method of condition-associated transcription variation

rax2:一个条件相关的转录变化的全基因组检测方法

Most mammalian genes have mRNA variants due to alternative promoter usage, alternative splicing, and alternative cleavage and polyadenylation. Expression of alternative RNA isoforms has been found to be associated with tumorigenesis, proliferation and differentiation. Detection of condition-associated transcription variation requires association methods. Traditional association methods such as Pearson chi-square test and Fisher Exact test are single test methods and do not work on count data with replicates. Although the Cochran Mantel Haenszel (CMH) approach can handle replicated count data, our simulations showed that multiple CMH tests still had very low power. To identify condition-associated variation of transcription, we here proposed a ranking analysis of chi-squares (RAX2) for large-scale association analysis. RAX2 is a nonparametric method and has accurate and conservative estimation of FDR profile. Simulations demonstrated that RAX2 performs well in finding condition-associated transcription variants. We applied RAX2 to primary T-cell transcriptomic data and identified 1610 (16.3%) tags associated in transcription with immune stimulation at FDR < 0.05. Most of these tags also had differential expression. Analysis of two and three tags within genes revealed that under immune stimulation short RNA isoforms were preferably used.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Methods Online

GBIS: the information system of the German Genebank

注硼系统:德国的基因库的信息系统

The German Federal ex situ Genebank of Agricultural and Horticultural Crop Species is the largest collection of its kind in the countries of the European Union and amongst the 10 largest collections worldwide. Beside its enormous scientific value as a safeguard of plant biodiversity, the plant genetic resources maintained are also of high importance for breeders to provide new impulses. The complex processes of managing such a collection are supported by the Genebank Information System (GBIS). GBIS is an important source of information for researchers and plant breeders, e.g. for identifying appropriate germplasm for breeding purposes. In addition, the access to genebank material as a sovereign task is also of high interest to the general public. Moreover, GBIS acts as a data source for global information systems, such as the Global Biodiversity Information Facility (GBIF) or the European Search Catalogue for Plant Genetic Resources (EURISCO).

Database URL: http://gbis.ipk-gatersleben.de/

[详细]

  • Database
  • 10年前
  • Original Article

CerebralWeb: a Cytoscape.js plug-in to visualize networks stratified by subcellular localization

cerebralweb:一cytoscape.js插件的可视化网络分层的亚细胞定位

CerebralWeb is a light-weight JavaScript plug-in that extends Cytoscape.js to enable fast and interactive visualization of molecular interaction networks stratified based on subcellular localization or other user-supplied annotation. The application is designed to be easily integrated into any website and is configurable to support customized network visualization. CerebralWeb also supports the automatic retrieval of Cerebral-compatible localizations for human, mouse and bovine genes via a web service and enables the automated parsing of Cytoscape compatible XGMML network files. CerebralWeb currently supports embedded network visualization on the InnateDB (www.innatedb.com) and Allergy and Asthma Portal (allergen.innatedb.com) database and analysis resources.

Database tool URL: http://www.innatedb.com/CerebralWeb

[详细]

  • Database
  • 10年前
  • Database Tool

MIsoMine: a genome-scale high-resolution data portal of expression, function and networks at the splice isoform level in the mouse

misomine:基因组规模的高分辨率数据门户的表达,在小鼠的剪接异构体水平和网络功能

Products of multiexon genes, especially in higher organisms, are a mixture of isoforms with different or even opposing functions, and therefore need to be treated separately. However, most studies and available resources such as Gene Ontology provide only gene-level function annotations, and therefore lose the differential information at the isoform level. Here we report MIsoMine, a high-resolution portal to multiple levels of functional information of alternatively spliced isoforms in the mouse. This data portal provides tissue-specific expression patterns and co-expression networks, along with such previously published functional genomic data as protein domains, predicted isoform-level functions and functional relationships. The core utility of MIsoMine is allowing users to explore a preprocessed, quality-controlled set of RNA-seq data encompassing diverse tissues and cell lineages. Tissue-specific co-expression networks were established, allowing a 2D ranking of isoforms and tissues by co-expression patterns. The results of the multiple isoforms of the same gene are presented in parallel to facilitate direct comparison, with cross-talking to prioritized functions at the isoform level. MIsoMine provides the first isoform-level resolution effort at genome-scale. We envision that this data portal will be a valuable resource for exploring functional genomic data, and will complement the existing functionalities of the mouse genome informatics database and the gene expression database for the laboratory mouse.

Database URL: http://guanlab.ccmb.med.umich.edu/misomine/

[详细]

  • Database
  • 10年前
  • Original Article