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Veröffentlichungen der HSWT

Die chronologische Liste zeigt aktuelle Veröffentlichungen aus dem Forschungsbetrieb der Hochschule Weihenstephan-Triesdorf. Zuständig ist das Zentrum für Forschung und Wissenstransfer (ZFW).

8 Ergebnisse

  • Matteo Togninalli, Ümit Seren, Jan A Freudenthal, J Grey Monroe, Dazhe Meng, Magnus Nordborg, Detlef Weigel, Karsten Borgwardt, Arthur Korte, Prof. Dr. Dominik Grimm

    • Berechtigungen:  Open Access
    • Berechtigungen:  Peer Reviewed

    AraPheno and the AraGWAS Catalog 2020: a major database update including RNA-Seq and knockout mutation data for Arabidopsis thaliana (2020) Nucleic Acids Research 48 (D1), S. D1063-D1068. DOI: 10.1093/nar/gkz925

    AbstractGenome-wide association studies (GWAS) are integral for studying genotype-phenotype relationships and gaining a deeper understanding of the genetic architecture underlying trait variation. A plethora of genetic associations between distinct loci and various traits have been successfully discovered and published for the model plant Arabidopsis thaliana. This success and the free availability of full genomes and phenotypic data for more than 1,000 different natural inbred lines led to the development of several data repositories. AraPheno (https://arapheno.1001genomes.org) serves as a central repository of population-scale phenotypes in A. thaliana, while the AraGWAS Catalog (https://aragwas.1001genomes.org) provides a publicly available, manually curated and standardized collection of marker-trait associations for all available phenotypes from AraPheno. In this major update, we introduce the next generation of both platforms, including new data, features and tools. We included novel results on associations between knockout-mutations and all AraPheno traits. Furthermore, AraPheno has been extended to display RNA-Seq data for hundreds of accessions, providing expression information for over 28 000 genes for these accessions. All data, including the imputed genotype matrix used for GWAS, are easily downloadable via the respective databases.
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  • Richa Bharti, Prof. Dr. Dominik Grimm

    • Berechtigungen:  Open Access
    • Berechtigungen:  Peer Reviewed

    Current challenges and best-practice protocols for microbiome analysis (2019) Briefings in Bioinformatics 22 (1), S. 178-193. DOI: 10.1093/bib/bbz155

    AbstractAnalyzing the microbiome of diverse species and environments using next-generation sequencing techniques has significantly enhanced our understanding on metabolic, physiological and ecological roles of environmental microorganisms. However, the analysis of the microbiome is affected by experimental conditions (e.g. sequencing errors and genomic repeats) and computationally intensive and cumbersome downstream analysis (e.g. quality control, assembly, binning and statistical analyses). Moreover, the introduction of new sequencing technologies and protocols led to a flood of new methodologies, which also have an immediate effect on the results of the analyses. The aim of this work is to review the most important workflows for 16S rRNA sequencing and shotgun and long-read metagenomics, as well as to provide best-practice protocols on experimental design, sample processing, sequencing, assembly, binning, annotation and visualization. To simplify and standardize the computational analysis, we provide a set of best-practice workflows for 16S rRNA and metagenomic sequencing data (available at https://github.com/grimmlab/MicrobiomeBestPracticeReview).

  • Peter Brown, . ..., Prof. Dr. Dominik Grimm, . ..., Yaoqi Zhou

    • Berechtigungen:  Open Access
    • Berechtigungen:  Peer Reviewed

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search (2019) Database 2019 . DOI: 10.1093/database/baz085

    AbstractDocument recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcHconsortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.

  • Elena Castellanos-Rizaldos, Xuan Zhang, Vasisht R. Tadigotla, Prof. Dr. Dominik Grimm, Chris Karlovich, Luis E. Raez, Johan K. Skog

    • Berechtigungen:  Open Access
    • Berechtigungen:  Peer Reviewed

    Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients (2019) Oncotarget 10 (30), S. 2911-2920. DOI: 10.18632/oncotarget.26885

    Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and its molecular landscape has been extensively studied. The most common genetic alterations in NSCLC are mutations within the epidermal growth factor receptor (EGFR) gene, with frequencies between 10-40%. There are several molecular targeted therapies for patients harboring these mutations.Liquid biopsies constitute a flexible approach to monitor these mutations in real time as opposed to tissue biopsies that represent a single snap-shot in time. However, interrogating cell free DNA (cfDNA) has inherent biological limitations, especially at early or localized disease stages, where there is not enough tumor material released into the patient’s circulation.We developed a qPCR- based test (ExoDx EGFR) that interrogates mutations within EGFR using Exosomal RNA/DNA and cfDNA (ExoNA) derived from plasma in a cohort of 110 NSCLC patients.The performance of the assay yielded an overall sensitivity of 90% for L858R, 83% for T790M and 73% for exon 19 indels with specificities of 100%, 100%, and 96% respectively. In a subcohort of patients with extrathoracic disease (M1b and MX) the sensitivities were 92% (L858R), 95% (T790M), and 86% (exon 19 indels) with specificity of 100%, 100% and 94% respectively.

  • Anja Gumpinger, Damian Roqueiro, Prof. Dr. Dominik Grimm, Karsten Borgwardt

    Methods and Tools in Genome-Wide Association Studies (2018) Computational Cell Biology . DOI: 10.1007/978-1-4939-8618-7_5

  • Elena Castellanos-Rizaldos, Prof. Dr. Dominik Grimm, Vasisht R. Tadigotla, James Hurley, John Healy, Patricia L. Neal, Mia Sher, Raajdeep Venkatesan, Chris Karlovich, Mitch Raponi, Anne Krug, Mikkel Noerholm, Jihane Tannous, Bakhos A. Tannous, Luis E. Raez, Johan K. Skog

    • Berechtigungen:  Open Access
    • Berechtigungen:  Peer Reviewed

    Exosome-Based Detection of EGFR T790M in Plasma from Non–Small Cell Lung Cancer Patients (2018) Clinical Cancer Research 24 (12), S. 2944-2950. DOI: 10.1158/1078-0432.CCR-17-3369

    Purpose: About 60% of non–small cell lung cancer (NSCLC) patients develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy through the EGFR T790M mutation. Patients with this mutation respond well to third-generation tyrosine kinase inhibitors, but obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Liquid biopsies using circulating free tumor DNA (cfDNA) have emerged as a noninvasive option to detect the mutation; however, sensitivity is low as many patients have too few detectable copies in circulation. Here, we have developed and validated a novel test that overcomes the limited abundance of the mutation by simultaneously capturing and interrogating exosomal RNA/DNA and cfDNA (exoNA) in a single step followed by a sensitive allele-specific qPCR.Experimental Design: ExoNA was extracted from the plasma of NSCLC patients with biopsy-confirmed T790M-positive (N = 102) and T790M-negative (N = 108) samples. The T790M mutation status was determined using an analytically validated allele-specific qPCR assay in a Clinical Laboratory Improvement Amendment laboratory.Results: Detection of the T790M mutation on exoNA achieved 92% sensitivity and 89% specificity using tumor biopsy results as gold standard. We also obtained high sensitivity (88%) in patients with intrathoracic disease (M0/M1a), for whom detection by liquid biopsy has been particularly challenging.Conclusions: The combination of exoRNA/DNA and cfDNA for T790M detection has higher sensitivity and specificity compared with historical cohorts using cfDNA alone. This could further help avoid unnecessary tumor biopsies for T790M mutation testing.

  • Jan M. Falcke, Neelanjan Bose, Alexander B. Artyukhin, Christian Rödelsperger, Gabriel V. Markov, Joshua J. Yim, Prof. Dr. Dominik Grimm, Marc H. Claassen, Oishika Panda, Joshua A. Baccile, Ying K. Zhang, Henry H. Le, Dino Jolic, Frank C. Schroeder, Ralf J. Sommer

    • Berechtigungen:  Open Access
    • Berechtigungen:  Peer Reviewed

    Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis (2018) Cell Chemical Biology 25 (6), S. 787-796. DOI: 10.1016/j.chembiol.2018.04.004

    In the nematodes Caenorhabditis elegans and Pristionchus pacificus, a modular library of small molecules control behavior, lifespan, and development. However, little is known about the final steps of their biosynthesis, in which diverse building blocks from primary metabolism are attached to glycosides of the dideoxysugar ascarylose, the ascarosides. We combine metabolomic analysis of natural isolates of P. pacificuswith genome-wide association mapping to identify a putative carboxylesterase, Ppa-uar-1, that is required for attachment of a pyrimidine-derived moiety in the biosynthesis of ubas#1, a major dauer pheromone component. Comparative metabolomic analysis of wild-type and Ppa-uar-1 mutants showed that Ppa-uar-1 is required specifically for the biosynthesis of ubas#1 and related metabolites. Heterologous expression of Ppa-UAR-1 in C. elegans yielded a non-endogenous ascaroside, whose structure confirmed that Ppa-uar-1 is involved in modification of a specific position in ascarosides. Our study demonstrates the utility of natural variation-based approaches for uncovering biosynthetic pathways.

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