Haarmann-Stemmann, T. | Search bioRxiv

bioRxiv2021

Duesselpore: a full-stack local web server for rapid and simple analysis of Oxford Nanopore Sequencing data

Genome-wide analysis of transcriptomes offers extensive insights into the molecular mechanisms underlying the physiology of all known species and discover those that are still hidden. Oxford Nanopore Technologies (ONT) has recently been developed as a fast, miniaturized, portable and a cost effective alternative to Next Generation Sequencing. However, RNA-seq data analysis software that exploit ONT portability and allows scientists to easily analyze ONT data everywhere without bioinformatic expertise is not widely available. We developed Duesselpore, an easy-to-follow deep sequencing workflow that runs as a local webserver and allows the analysis of ONT data everywhere without requiring additional bioinformatic tools or internet connection. Duesselpore output includes differentially expressed genes and further downstream analyses, such as variance heatmap, disease and gene ontology plots, gene concept network plots and exports customized pathways for different cellular processes. We validated Duesselpore by analyzing the transcriptomic changes induced by PCB126, a dioxin-like PCB and a potent aryl hydrocarbon receptor (AhR) agonist in human HaCaT keratinocytes, a well characterized model system. Duesselpore was specifically developed to analyze ONT data but we also implemented NGS data analysis. Duesselpore is compatible with Microsoft and Mac operating systems, allows convenient, reliable and cost-effective analysis of ONT and NGS data.

bioinformatics↗

bioRxiv2020

DIETARY MONOTERPENOIDS AS A NEW CLASS OF ALLOSTERIC HUMAN ARYL HYDROCARBON RECEPTOR ANTAGONISTS

Carvones, the constituents of essential oils of dill, caraway, and spearmint, were reported to antagonize the human aryl hydrocarbon receptor (AhR); however, the exact molecular mechanism remains elusive. We show that carvones are non-competitive allosteric antagonists of the AhR that inhibit the induction of AhR target genes in a ligand-selective and cell type-specific manner. Carvones do not displace radiolabeled ligand from binding at the AhR, but they bind allosterically within the bHLH/PAS-A region of the AhR. Carvones did not influence a translocation of ligand-activated AhR into the nucleus. Carvones inhibited the heterodimerization of the AhR with its canonical partner ARNT and subsequent binding of the AhR to the promotor of CYP1A1. Interaction of carvones with potential off-targets, including ARNT and protein kinases, was refuted. This is the first report of a small dietary monoterpenoids as a new class of AhR non-competitive allosteric antagonists with the potential preventive and therapeutic application.

pharmacology and toxicology↗