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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: Preoperative chemotherapy without histological confirmation by biopsy without minimal‐invasive diagnostic markers confirming nephroblastoma diagnosis are highly warranted.
Abstract: Background Nephroblastoma (or Wilms tumor—WT) is the most common childhood kidney cancer. In Europe, nephroblastoma is treated with preoperative chemotherapy without histological confirmation by biopsy. Therefore, minimal-invasive diagnostic markers confirming nephroblastoma diagnosis are highly warranted. Procedure In our study, we aim to identify circulating miRNAs with diagnostic potential for differentiating nephroblastoma from controls. We determined the level of 19 miRNAs in serum of 32 patients with nephroblastoma and 12 controls with quantitative real-time PCR. Three miRNAs were further tested in an independent validation set including sera of patients with renal tumors other than Wilms. Results In total, 14 miRNAs showed significantly higher abundance in serum of patients with nephroblastoma than in controls. The miRNAs with highest diagnostic potentials included miRs-130b-3p, -100-5p, and -143-3p with an AUC of 0.94, 0.90, and 0.89, respectively. A signature based on these three miRNAs to differentiated patients from controls with an accuracy of 84.58%, a sensitivity of 76.67%, and a specificity of 92.5%. Higher expression of miRs-100-5p and -130b-3p was confirmed in an independent validation set. The signature based on miRs-100-5p and -130b-3p differentiated patients with nephroblastoma from healthy controls with an accuracy, sensitivity, and specificity of 79.6%, 69.2%, and 90.0%, respectively. Conclusion In summary, we provide first evidence that serum miR-100-5p and -130b-3p hold potential as biomarker for WT irrespective of the subtype and that expression level of these miRNA in serum is unaffected by differences in serum collection. Pediatr Blood Cancer 2015;62:1360–1367. © 2015 Wiley Periodicals, Inc.

50 citations

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TL;DR: The aim of the present article is to outline the most relevant computational and experimental methods applied in the field of lectin-carbohydrate interaction and to give an overview of the current state of the art in the modeling of these interactions with a focus on plant lectins.

49 citations

Journal ArticleDOI
TL;DR: MiRTargetLink 2.0 as mentioned in this paper is an all-in-one solution for human, mouse and rat miRNA networks, where users can input in the unidirectional search mode either a single gene, gene set or gene pathway, alternatively a single miRNA, a set of miRNAs or an miRNA pathway.
Abstract: Which genes, gene sets or pathways are regulated by certain miRNAs? Which miRNAs regulate a particular target gene or target pathway in a certain physiological context? Answering such common research questions can be time consuming and labor intensive. Especially for researchers without computational experience, the integration of different data sources, selection of the right parameters and concise visualization can be demanding. A comprehensive analysis should be central to present adequate answers to complex biological questions. With miRTargetLink 2.0, we develop an all-in-one solution for human, mouse and rat miRNA networks. Users input in the unidirectional search mode either a single gene, gene set or gene pathway, alternatively a single miRNA, a set of miRNAs or an miRNA pathway. Moreover, genes and miRNAs can jointly be provided to the tool in the bidirectional search mode. For the selected entities, interaction graphs are generated from different data sources and dynamically presented. Connected application programming interfaces (APIs) to the tailored enrichment tools miEAA and GeneTrail facilitate downstream analysis of pathways and context-annotated categories of network nodes. MiRTargetLink 2.0 is freely accessible at https://www.ccb.uni-saarland.de/mirtargetlink2.

49 citations

Journal ArticleDOI
TL;DR: It is proved that GeneTrail offers a flexible and user-adapted way to identify functional categories in large-scale plant transcriptome data sets and that the nas4x-1 mutant was defective in metal homeostasis.
Abstract: Background: High-throughput technologies have opened new avenues to study biological processes and pathways. The interpretation of the immense amount of data sets generated nowadays needs to be facilitated in order to enable biologists to identify complex gene networks and functional pathways. To cope with this task multiple computer-based programs have been developed. GeneTrail is a freely available online tool that screens comparative transcriptomic data for differentially regulated functional categories and biological pathways extracted from common data bases like KEGG, Gene Ontology (GO), TRANSPATH and TRANSFAC. Additionally, GeneTrail offers a feature that allows screening of individually defined biological categories that are relevant for the respective research topic. Results: We have set up GeneTrail for the use of Arabidopsis thaliana. To test the functionality of this tool for plant analysis, we generated transcriptome data of root and leaf responses to Fe deficiency and the Arabidopsis metal homeostasis mutant nas4x-1. We performed Gene Set Enrichment Analysis (GSEA) with eight meaningful pairwise comparisons of transcriptome data sets. We were able to uncover several functional pathways including metal homeostasis that were affected in our experimental situations. Representation of the differentially regulated functional categories in Venn diagrams uncovered regulatory networks at the level of whole functional pathways. Over-Representation Analysis (ORA) of differentially regulated genes identified in pairwise comparisons revealed specific functional plant physiological categories as major targets upon Fe deficiency and in nas4x-1. Conclusion: Here, we obtained supporting evidence, that the nas4x-1 mutant was defective in metal homeostasis. It was confirmed that nas4x-1 showed Fe deficiency in roots and signs of Fe deficiency and Fe sufficiency in leaves. Besides metal homeostasis, biotic stress, root carbohydrate, leaf photosystem and specific cell biological categories were discovered as main targets for regulated changes in response to - Fe and nas4x-1. Among 258 differentially expressed genes in response to - Fe and nas4x-1 five functional categories were enriched covering metal homeostasis, redox regulation, cell division and histone acetylation. We proved that GeneTrail offers a flexible and user-adapted way to identify functional categories in large-scale plant transcriptome data sets. The distinguished feature that allowed analysis of individually assembled functional categories facilitated the study of the Arabidopsis thaliana transcriptome.

49 citations

Journal ArticleDOI
TL;DR: This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late‐stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections.
Abstract: Staphylococcus aureus Clp ATPases (molecular chaperones) alter normal physiological functions including an aconitase-mediated effect on post-stationary growth, acetate catabolism, and entry into death phase (Chatterjee et al., J. Bacteriol. 2005, 187, 4488-4496). In the present study, the global function of ClpC in physiology, metabolism, and late-stationary phase survival was examined using DNA microarrays and 2-D PAGE followed by MALDI-TOF MS. The results suggest that ClpC is involved in regulating the expression of genes and/or proteins of gluconeogenesis, the pentose-phosphate pathway, pyruvate metabolism, the electron transport chain, nucleotide metabolism, oxidative stress, metal ion homeostasis, stringent response, and programmed cell death. Thus, one major function of ClpC is balancing late growth phase carbon metabolism. Furthermore, these changes in carbon metabolism result in alterations of the intracellular concentration of free NADH, the amount of cell-associated iron, and fatty acid metabolism. This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late-stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections.

48 citations


Cited by
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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