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Rainer Breitling

Bio: Rainer Breitling is an academic researcher from University of Manchester. The author has contributed to research in topics: Synthetic biology & Metabolomics. The author has an hindex of 65, co-authored 233 publications receiving 19231 citations. Previous affiliations of Rainer Breitling include University of Glasgow & University of Groningen.


Papers
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Journal ArticleDOI
TL;DR: AntiSMASH as mentioned in this paper is a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.org.
Abstract: Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software.

1,691 citations

Journal ArticleDOI
TL;DR: An analysis of the physiological function of the identified genes indicates that the RP approach is powerful for identifying biologically relevant expression changes and can lead to a sharp reduction in the number of replicate experiments needed to obtain reproducible results.

1,557 citations

Journal ArticleDOI
TL;DR: This work presents the first comprehensive pipeline capable of identifying biosynthetic loci covering the whole range of known secondary metabolite compound classes, and integrates or cross-links all previously available secondary-metabolite specific gene analysis methods in one interactive view.
Abstract: Bacterial and fungal secondary metabolism is a rich source of novel bioactive compounds with potential pharmaceutical applications as antibiotics, anti-tumor drugs or cholesterol-lowering drugs To find new drug candidates, microbiologists are increasingly relying on sequencing genomes of a wide variety of microbes However, rapidly and reliably pinpointing all the potential gene clusters for secondary metabolites in dozens of newly sequenced genomes has been extremely challenging, due to their biochemical heterogeneity, the presence of unknown enzymes and the dispersed nature of the necessary specialized bioinformatics tools and resources Here, we present antiSMASH (antibiotics & Secondary Metabolite Analysis Shell), the first comprehensive pipeline capable of identifying biosynthetic loci covering the whole range of known secondary metabolite compound classes (polyketides, non-ribosomal peptides, terpenes, aminoglycosides, aminocoumarins, indolocarbazoles, lantibiotics, bacteriocins, nucleosides, beta-lactams, butyrolactones, siderophores, melanins and others) It aligns the identified regions at the gene cluster level to their nearest relatives from a database containing all other known gene clusters, and integrates or cross-links all previously available secondary-metabolite specific gene analysis methods in one interactive view antiSMASH is available at http://antismashsecondarymetabolitesorg

1,496 citations

Journal ArticleDOI
TL;DR: The thoroughly updated antiSMASH version 4 is presented, which adds several novel features, including prediction of gene cluster boundaries using the ClusterFinder method or the newly integrated CASSIS algorithm, improved substrate specificity prediction for non-ribosomal peptide synthetase adenylation domains based on the new SANDPUMA algorithm, and several usability features have been updated and improved.
Abstract: Many antibiotics, chemotherapeutics, crop protection agents and food preservatives originate from molecules produced by bacteria, fungi or plants. In recent years, genome mining methodologies have been widely adopted to identify and characterize the biosynthetic gene clusters encoding the production of such compounds. Since 2011, the â € antibiotics and secondary metabolite analysis shell - antiSMASH' has assisted researchers in efficiently performing this, both as a web server and a standalone tool. Here, we present the thoroughly updated antiSMASH version 4, which adds several novel features, including prediction of gene cluster boundaries using the ClusterFinder method or the newly integrated CASSIS algorithm, improved substrate specificity prediction for non-ribosomal peptide synthetase adenylation domains based on the new SANDPUMA algorithm, improved predictions for terpene and ribosomally synthesized and post-translationally modified peptides cluster products, reporting of sequence similarity to proteins encoded in experimentally characterized gene clusters on a per-protein basis and a domain-level alignment tool for comparative analysis of trans-AT polyketide synthase assembly line architectures. Additionally, several usability features have been updated and improved. Together, these improvements make antiSMASH up-to-date with the latest developments in natural product research and will further facilitate computational genome mining for the discovery of novel bioactive molecules.

1,043 citations

Journal ArticleDOI
TL;DR: The highly improved antiSMASH 2.0 now supports input of multiple related sequences simultaneously (multi-FASTA/GenBank/EMBL), which allows the analysis of draft genomes comprising multiple contigs, and direct analysis of protein sequences is now possible.
Abstract: Microbial secondary metabolites are a potent source of antibiotics and other pharmaceuticals. Genome mining of their biosynthetic gene clusters has become a key method to accelerate their identification and characterization. In 2011, we developed antiSMASH, a web-based analysis platform that automates this process. Here, we present the highly improved antiSMASH 2.0 release, available at http://antismash.secondarymetabolites.org/. For the new version, antiSMASH was entirely re-designed using a plug-and-play concept that allows easy integration of novel predictor or output modules. antiSMASH 2.0 now supports input of multiple related sequences simultaneously (multi-FASTA/GenBank/EMBL), which allows the analysis of draft genomes comprising multiple contigs. Moreover, direct analysis of protein sequences is now possible. antiSMASH 2.0 has also been equipped with the capacity to detect additional classes of secondary metabolites, including oligosaccharide antibiotics, phenazines, thiopeptides, homo-serine lactones, phosphonates and furans. The algorithm for predicting the core structure of the cluster end product is now also covering lantipeptides, in addition to polyketides and non-ribosomal peptides. The antiSMASH ClusterBlast functionality has been extended to identify sub-clusters involved in the biosynthesis of specific chemical building blocks. The new features currently make antiSMASH 2.0 the most comprehensive resource for identifying and analyzing novel secondary metabolite biosynthetic pathways in microorganisms.

773 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: The survey will help tool designers/developers and experienced end users understand the underlying algorithms and pertinent details of particular tool categories/tools, enabling them to make the best choices for their particular research interests.
Abstract: Functional analysis of large gene lists, derived in most cases from emerging high-throughput genomic, proteomic and bioinformatics scanning approaches, is still a challenging and daunting task. The gene-annotation enrichment analysis is a promising high-throughput strategy that increases the likelihood for investigators to identify biological processes most pertinent to their study. Approximately 68 bioinformatics enrichment tools that are currently available in the community are collected in this survey. Tools are uniquely categorized into three major classes, according to their underlying enrichment algorithms. The comprehensive collections, unique tool classifications and associated questions/issues will provide a more comprehensive and up-to-date view regarding the advantages, pitfalls and recent trends in a simpler tool-class level rather than by a tool-by-tool approach. Thus, the survey will help tool designers/developers and experienced end users understand the underlying algorithms and pertinent details of particular tool categories/tools, enabling them to make the best choices for their particular research interests.

13,102 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
TL;DR: A basic taxonomy of feature selection techniques is provided, providing their use, variety and potential in a number of both common as well as upcoming bioinformatics applications.
Abstract: Feature selection techniques have become an apparent need in many bioinformatics applications. In addition to the large pool of techniques that have already been developed in the machine learning and data mining fields, specific applications in bioinformatics have led to a wealth of newly proposed techniques. In this article, we make the interested reader aware of the possibilities of feature selection, providing a basic taxonomy of feature selection techniques, and discussing their use, variety and potential in a number of both common as well as upcoming bioinformatics applications. Contact: yvan.saeys@psb.ugent.be Supplementary information: http://bioinformatics.psb.ugent.be/supplementary_data/yvsae/fsreview

4,706 citations

Journal ArticleDOI
TL;DR: GOrilla is a web-based application that identifies enriched GO terms in ranked lists of genes, without requiring the user to provide explicit target and background sets, and its unique features and advantages over other threshold free enrichment tools include rigorous statistics, fast running time and an effective graphical representation.
Abstract: Since the inception of the GO annotation project, a variety of tools have been developed that support exploring and searching the GO database In particular, a variety of tools that perform GO enrichment analysis are currently available Most of these tools require as input a target set of genes and a background set and seek enrichment in the target set compared to the background set A few tools also exist that support analyzing ranked lists The latter typically rely on simulations or on union-bound correction for assigning statistical significance to the results GOrilla is a web-based application that identifies enriched GO terms in ranked lists of genes, without requiring the user to provide explicit target and background sets This is particularly useful in many typical cases where genomic data may be naturally represented as a ranked list of genes (eg by level of expression or of differential expression) GOrilla employs a flexible threshold statistical approach to discover GO terms that are significantly enriched at the top of a ranked gene list Building on a complete theoretical characterization of the underlying distribution, called mHG, GOrilla computes an exact p-value for the observed enrichment, taking threshold multiple testing into account without the need for simulations This enables rigorous statistical analysis of thousand of genes and thousands of GO terms in order of seconds The output of the enrichment analysis is visualized as a hierarchical structure, providing a clear view of the relations between enriched GO terms GOrilla is an efficient GO analysis tool with unique features that make a useful addition to the existing repertoire of GO enrichment tools GOrilla's unique features and advantages over other threshold free enrichment tools include rigorous statistics, fast running time and an effective graphical representation GOrilla is publicly available at: http://cbl-gorillacstechnionacil

3,157 citations