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Author

Hans-Peter Lenhof

Other affiliations: Max Planck Society
Bio: Hans-Peter Lenhof is an academic researcher from Saarland University. The author has contributed to research in topics: Macromolecular docking & Autoantibody. The author has an hindex of 44, co-authored 164 publications receiving 6046 citations. Previous affiliations of Hans-Peter Lenhof include Max Planck Society.


Papers
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Journal ArticleDOI
TL;DR: The updated version of miRPathDB, with its new custom-tailored features, is one of the most comprehensive and advanced resources for miRNAs and their target pathways.
Abstract: Since the initial release of miRPathDB, tremendous progress has been made in the field of microRNA (miRNA) research. New miRNA reference databases have emerged, a vast amount of new miRNA candidates has been discovered and the number of experimentally validated target genes has increased considerably. Hence, the demand for a major upgrade of miRPathDB, including extended analysis functionality and intuitive visualizations of query results has emerged. Here, we present the novel release 2.0 of the miRNA Pathway Dictionary Database (miRPathDB) that is freely accessible at https://mpd.bioinf.uni-sb.de/. miRPathDB 2.0 comes with a ten-fold increase of pre-processed data. In total, the updated database provides putative associations between 27 452 (candidate) miRNAs, 28 352 targets and 16 833 pathways for Homo sapiens, as well as interactions of 1978 miRNAs, 24 898 targets and 6511 functional categories for Mus musculus. Additionally, we analyzed publications citing miRPathDB to identify common use-cases and further extensions. Based on this evaluation, we added new functionality for interactive visualizations and down-stream analyses of bulk queries. In summary, the updated version of miRPathDB, with its new custom-tailored features, is one of the most comprehensive and advanced resources for miRNAs and their target pathways.

104 citations

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TL;DR: This study represents a comprehensive theoretical analysis of the relationship between miRNAs and their predicted target pathways, and provides a ‘miRNA-target pathway’ dictionary, which enables researchers to identify target pathways of differentially regulated mi RNAs.
Abstract: While in the last decade mRNA expression profiling was among the most popular research areas, over the past years the study of non-coding RNAs, especially microRNAs (miRNAs), has gained increasing interest. For almost 900 known human miRNAs hundreds of pretended targets are known. However, there is only limited knowledge about putative systemic effects of changes in the expression of miRNAs and their regulatory influence. We determined for each known miRNA the biochemical pathways in the KEGG and TRANSPATH database and the Gene Ontology categories that are enriched with respect to its target genes. We refer to these pathways and categories as target pathways of the corresponding miRNA. Investigating target pathways of miRNAs we found a strong relation to disease-related regulatory pathways, including mitogen-activated protein kinase (MAPK) signaling cascade, Transforming growth factor (TGF)-beta signaling pathway or the p53 network. Performing a sophisticated analysis of differentially expressed genes of 13 cancer data sets extracted from gene expression omnibus (GEO) showed that targets of specific miRNAs were significantly deregulated in these sets. The respective miRNA target analysis is also a novel part of our gene set analysis pipeline GeneTrail. Our study represents a comprehensive theoretical analysis of the relationship between miRNAs and their predicted target pathways. Our target pathways analysis provides a 'miRNA-target pathway' dictionary, which enables researchers to identify target pathways of differentially regulated miRNAs.

104 citations

Journal ArticleDOI
TL;DR: This work proposes a novel formulation allowing for numerical solutions for the nontrivial molecular geometries arising in the applications mentioned before, based on the introduction of a secondary field psi, which acts as the potential for the rotation free part of the dielectric displacement field D.
Abstract: The accurate modeling of the dielectric properties of water is crucial for many applications in physics, computational chemistry, and molecular biology. This becomes possible in the framework of nonlocal electrostatics, for which we propose a novel formulation allowing for numerical solutions for the nontrivial molecular geometries arising in the applications mentioned before. Our approach is based on the introduction of a secondary field $\ensuremath{\psi}$, which acts as the potential for the rotation free part of the dielectric displacement field $\mathbf{D}$. For many relevant models, the dielectric function of the medium can be expressed as the Green's function of a local differential operator. In this case, the resulting coupled Poisson (-Boltzmann) equations for $\ensuremath{\psi}$ and the electrostatic potential $\ensuremath{\phi}$ reduce to a system of coupled partial differential equations. The approach is illustrated by its application to simple geometries.

103 citations

Journal ArticleDOI
TL;DR: The miRNA Pathway Dictionary Database (miRPathDB) is introduced, freely accessible at https://mpd.bioinf.uni-sb.de/ and aims to complement available target pathway web-servers by providing researchers easy access to the information which pathways are regulated by a miRNA, which miRNAs target a pathway and how specific these regulations are.
Abstract: In the last decade, miRNAs and their regulatory mechanisms have been intensively studied and many tools for the analysis of miRNAs and their targets have been developed. We previously presented a dictionary on single miRNAs and their putative target pathways. Since then, the number of miRNAs has tripled and the knowledge on miRNAs and targets has grown substantially. This, along with changes in pathway resources such as KEGG, leads to an improved understanding of miRNAs, their target genes and related pathways. Here, we introduce the miRNA Pathway Dictionary Database (miRPathDB), freely accessible at https://mpd.bioinf.uni-sb.de/ With the database we aim to complement available target pathway web-servers by providing researchers easy access to the information which pathways are regulated by a miRNA, which miRNAs target a pathway and how specific these regulations are. The database contains a large number of miRNAs (2595 human miRNAs), different miRNA target sets (14 773 experimentally validated target genes as well as 19 281 predicted targets genes) and a broad selection of functional biochemical categories (KEGG-, WikiPathways-, BioCarta-, SMPDB-, PID-, Reactome pathways, functional categories from gene ontology (GO), protein families from Pfam and chromosomal locations totaling 12 875 categories). In addition to Homo sapiens, also Mus musculus data are stored and can be compared to human target pathways.

100 citations

Journal ArticleDOI
TL;DR: It is shown that blood miRNA signatures are suitable to distinguish lung cancer from COPD.

100 citations


Cited by
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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

Journal ArticleDOI
TL;DR: These revisions simplify the McDonald Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Abstract: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

8,883 citations

Journal ArticleDOI
TL;DR: A new method for multiple sequence alignment that provides a dramatic improvement in accuracy with a modest sacrifice in speed as compared to the most commonly used alternatives but avoids the most serious pitfalls caused by the greedy nature of this algorithm.

6,727 citations

Journal ArticleDOI
TL;DR: A biologist-oriented portal that provides a gene list annotation, enrichment and interactome resource and enables integrated analysis of multi-OMICs datasets, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.
Abstract: A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era

6,282 citations

Journal ArticleDOI
TL;DR: A significant update to one of the tools in this domain called Enrichr, a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries is presented.
Abstract: Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.

6,201 citations