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  • 1
    Publication Date: 2015-09-11
    Description: Motivation: Identification of differentially expressed genes is an important step in extracting knowledge from gene expression profiling studies. The raw expression data from microarray and other high-throughput technologies is deposited into the Gene Expression Omnibus (GEO) and served as Simple Omnibus Format in Text (SOFT) files. However, to extract and analyze differentially expressed genes from GEO requires significant computational skills. Results: Here we introduce GEO2Enrichr, a browser extension for extracting differentially expressed gene sets from GEO and analyzing those sets with Enrichr, an independent gene set enrichment analysis tool containing over 70 000 annotated gene sets organized into 75 gene-set libraries. GEO2Enrichr adds JavaScript code to GEO web-pages; this code scrapes user selected accession numbers and metadata, and then, with one click, users can submit this information to a web-server application that downloads the SOFT files, parses, cleans and normalizes the data, identifies the differentially expressed genes, and then pipes the resulting gene lists to Enrichr for downstream functional analysis. GEO2Enrichr opens a new avenue for adding functionality to major bioinformatics resources such GEO by integrating tools and resources without the need for a plug-in architecture. Importantly, GEO2Enrichr helps researchers to quickly explore hypotheses with little technical overhead, lowering the barrier of entry for biologists by automating data processing steps needed for knowledge extraction from the major repository GEO. Availability and implementation: GEO2Enrichr is an open source tool, freely available for installation as browser extensions at the Chrome Web Store and FireFox Add-ons. Documentation and a browser independent web application can be found at http://amp.pharm.mssm.edu/g2e/ . Contact: avi.maayan@mssm.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 2
    Publication Date: 2016-06-01
    Description: Motivation: The human microbiome plays a key role in health and disease. Thanks to comparative metatranscriptomics, the cellular functions that are deregulated by the microbiome in disease can now be computationally explored. Unlike gene-centric approaches, pathway-based methods provide a systemic view of such functions; however, they typically consider each pathway in isolation and in its entirety. They can therefore overlook the key differences that (i) span multiple pathways, (ii) contain bidirectionally deregulated components, (iii) are confined to a pathway region. To capture these properties, computational methods that reach beyond the scope of predefined pathways are needed. Results: By integrating an existing module discovery algorithm into comparative metatranscriptomic analysis, we developed metaModules, a novel computational framework for automated identification of the key functional differences between health- and disease-associated communities. Using this framework, we recovered significantly deregulated subnetworks that were indeed recognized to be involved in two well-studied, microbiome-mediated oral diseases, such as butanoate production in periodontal disease and metabolism of sugar alcohols in dental caries. More importantly, our results indicate that our method can be used for hypothesis generation based on automated discovery of novel, disease-related functional subnetworks, which would otherwise require extensive and laborious manual assessment. Availability and implementation: metaModules is available at https://bitbucket.org/alimay/metamodules/ Contact: a.may@vu.nl or s.abeln@vu.nl Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 3
    Publication Date: 2016-06-01
    Description: Motivation: Haplotype assembly is the computational problem of reconstructing haplotypes in diploid organisms and is of fundamental importance for characterizing the effects of single-nucleotide polymorphisms on the expression of phenotypic traits. Haplotype assembly highly benefits from the advent of ‘future-generation’ sequencing technologies and their capability to produce long reads at increasing coverage. Existing methods are not able to deal with such data in a fully satisfactory way, either because accuracy or performances degrade as read length and sequencing coverage increase or because they are based on restrictive assumptions. Results: By exploiting a feature of future-generation technologies—the uniform distribution of sequencing errors—we designed an exact algorithm, called H ap C ol , that is exponential in the maximum number of corrections for each single-nucleotide polymorphism position and that minimizes the overall error-correction score. We performed an experimental analysis, comparing H ap C ol with the current state-of-the-art combinatorial methods both on real and simulated data. On a standard benchmark of real data, we show that H ap C ol is competitive with state-of-the-art methods, improving the accuracy and the number of phased positions. Furthermore, experiments on realistically simulated datasets revealed that H ap C ol requires significantly less computing resources, especially memory. Thanks to its computational efficiency, H ap C ol can overcome the limits of previous approaches, allowing to phase datasets with higher coverage and without the traditional all-heterozygous assumption. Availability and implementation: Our source code is available under the terms of the GNU General Public License at http://hapcol.algolab.eu/ . Contact: bonizzoni@disco.unimib.it Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 4
    Publication Date: 2016-09-02
    Description: : Finding and translating stretches of DNA lacking stop codons is a task common in the analysis of sequence data. However, the computational tools for finding open reading frames are sufficiently slow that they are becoming a bottleneck as the volume of sequence data grows. This computational bottleneck is especially problematic in metagenomics when searching unassembled reads, or screening assembled contigs for genes of interest. Here, we present OrfM, a tool to rapidly identify open reading frames (ORFs) in sequence data by applying the Aho–Corasick algorithm to find regions uninterrupted by stop codons. Benchmarking revealed that OrfM finds identical ORFs to similar tools (‘GetOrf’ and ‘Translate’) but is four-five times faster. While OrfM is sequencing platform-agnostic, it is best suited to large, high quality datasets such as those produced by Illumina sequencers. Availability and Implementation: Source code and binaries are freely available for download at http://github.com/wwood/OrfM or through GNU Guix under the LGPL 3+ license. OrfM is implemented in C and supported on GNU/Linux and OSX. Contacts: b.woodcroft@uq.edu.au Supplementary information : Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 5
    Publication Date: 2015-09-22
    Description: Motivation: Integrative network analysis methods provide robust interpretations of differential high-throughput molecular profile measurements. They are often used in a biomedical context—to generate novel hypotheses about the underlying cellular processes or to derive biomarkers for classification and subtyping. The underlying molecular profiles are frequently measured and validated on animal or cellular models. Therefore the results are not immediately transferable to human. In particular, this is also the case in a study of the recently discovered interleukin-17 producing helper T cells (Th17), which are fundamental for anti-microbial immunity but also known to contribute to autoimmune diseases. Results: We propose a mathematical model for finding active subnetwork modules that are conserved between two species. These are sets of genes, one for each species, which (i) induce a connected subnetwork in a species-specific interaction network, (ii) show overall differential behavior and (iii) contain a large number of orthologous genes. We propose a flexible notion of conservation, which turns out to be crucial for the quality of the resulting modules in terms of biological interpretability. We propose an algorithm that finds provably optimal or near-optimal conserved active modules in our model. We apply our algorithm to understand the mechanisms underlying Th17 T cell differentiation in both mouse and human. As a main biological result, we find that the key regulation of Th17 differentiation is conserved between human and mouse. Availability and implementation: xHeinz, an implementation of our algorithm, as well as all input data and results, are available at http://software.cwi.nl/xheinz and as a Galaxy service at http://services.cbib.u-bordeaux2.fr/galaxy in CBiB Tools. Contact: gunnar.klau@cwi.nl Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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