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Our understanding of mesial temporal lobe epilepsy (MTLE), one of the most common form of drug-resistant epilepsy in humans, is derived mainly from clinical, imaging, and physiological data from humans and animal models. High-throughput gene expression studies of human MTLE have the potential to uncover molecular changes underlying disease pathogenesis along with novel therapeutic targets. Using RNA- and small RNA-sequencing in parrallel, we explored differentially expressed genes in the hippocampus and cortex of MTLE patients who had undergone surgical resection and non-epileptic controls. We identified differentially expressed genes in the hippocampus of MTLE patients and differentially expressed small RNAs across both the cortex and hippocampus. We found significant enrichment for astrocytic and microglial genes among up-regulated genes, and down regulation of neuron specific genes in the hippocampus of MTLE patients. The transcriptome profile of the small RNAs reflected disease state more robustly than mRNAs, even across brain regions which show very little pathology. While mRNAs segregated predominately by brain region for MTLE and controls, small RNAs segregated by disease state. In particular, our data suggest that specific miRNAs (e.g., let-7b-3p and let-7c-3p) may be key regulators of multiple pathways related to MTLE pathology. Further, we report a strong association of other small RNA species with MTLE pathology. As such we have uncovered novel elements that may contribute to the establishment and progression of MTLE pathogenesis and that could be leveraged as therapeutic targets.
Pubmed ID: 31533065
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An Internet library offering the general public access to historical collections that exist in digital format including texts, audio, moving images, and software. Additionally it provides archived web pages in their collections, and specialized services for adaptive reading and information access for the blind and other persons with disabilities. Founded in 1996 and located in San Francisco, the Archive has been receiving data donations from Alexa Internet and others. In late 1999, the organization started to grow to include more well-rounded collections.
View all literature mentionsA catalog of gene-expression data collected from human cells treated with chemical compounds and genetic reagents. Computational methods to reduce the number of necessary genomic measurements along with streamlined methodologies enable the current effort to significantly increase the size of the CMap database and along with it, our potential to connect human diseases with the genes that underlie them and the drugs that treat them. The NIH has funded a large expansion of the Connectivity Map dataset through the Library of Integrated Network-based Cellular Signatures (LINCS). The Broad Institute's LINCS center aims to create a first installment of data generation and analysis for the LINCS program. Through these data LINCS intends to accelerate the discovery process by systematically revealing connections between genes/compounds discovered in screens and molecular pathways that underlie disease states.
View all literature mentionsCentral online repository for microRNA nomenclature, sequence data, annotation and target prediction.Collection of published miRNA sequences and annotation.
View all literature mentionsSoftware package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsHuman and mouse genome annotation project which aims to identify all gene features in the human genome using computational analysis, manual annotation, and experimental validation.
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