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IMA-08401 (C2) is a novel aryl hydrocarbon receptor (AHR) agonist and selective AHR modulator (SAHRM) that is structurally similar to laquinimod (LAQ). Both compounds are converted to the AHR-active metabolite DELAQ (IMA-06201) in vivo. SAHRMs have been proposed as therapeutic options for various autoimmune disorders. Clinical trials on LAQ have not reported any significant toxic outcomes and C2 has shown low toxicity in rats; however, their functional resemblance to the highly toxic AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) raises questions. Here, we characterize the hepatic transcriptomic changes induced by acute (single-dose) and subacute exposure (repeated dosing for 5 days followed by a 5-day recovery period) to C2 in Sprague-Dawley rats. Exposure to C2 leads to activation of the AHR, as shown by altered transcription of Cyp1a1. We identify a heightened response early after exposure that drops off by day 10. Acute exposure to C2 leads to changes to transcription of genes involved in antiviral and antibacterial responses, which highlights the immunomodulator effects of this AHR agonist. Subacute exposure causes an oxidative stress response in the liver, the consequences of which require further study on target tissues such as the CNS and immune system, both of which may be compromised in this patient population.
Pubmed ID: 30893768
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GoMiner is a tool for biological interpretation of "omic" data including data from gene expression microarrays. Omic experiments often generate lists of dozens or hundreds of genes that differ in expression between samples, raising the question, What does it all mean biologically? To answer this question, GoMiner leverages the Gene Ontology (GO) to identify the biological processes, functions and components represented in these lists. Instead of analyzing microarray results with a gene-by-gene approach, GoMiner classifies the genes into biologically coherent categories and assesses these categories. The insights gained through GoMiner can generate hypotheses to guide additional research. GoMiner displays the genes within the framework of the Gene Ontology hierarchy in two ways: * In the form of a tree, similar to that in AmiGO * In the form of a "Directed Acyclic Graph" (DAG) The program also provides: * Quantitative and statistical analysis * Seamless integration with important public databases GoMiner uses the databases provided by the GO Consortium. These databases combine information from a number of different consortium participants, include information from many different organisms and data sources, and are referenced using a variety of different gene product identification approaches.
View all literature mentionsSoftware providing a set of functions to generate high-resolution Venn and Euler plots. Includes handling for several special cases, including two-case scaling, and extensive customization of plot shape and structure.
View all literature mentionsDatabase for genomes that have been completely sequenced, have active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. Includes nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases. All entries follow NCBI's format for data collections. Content of Entrez Gene represents result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. Content is updated as new information becomes available.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsSoftware R package of functions and classes for the analysis of oligonucleotide arrays manufactured by Affymetrix. Used to process probe level data and for exploratory oligonucleotide array analysis.
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