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Ray Dingledine

Publications and source records attributed to Ray Dingledine.

2 recordsLinked to original sources

Text mining functional keywords associated with genes.

Modern experimental techniques provide the ability to gather vast amounts of biological data in a single experiment (e.g. DNA microarray experiment), making it extremely difficult for the researcher to interpret the data and form conclusions about the functions of the genes. Current approaches provide useful information that organizes or relates genes, but a major shortcoming is they either do not address specific functions of the genes or are constrained by functions predefined in other databases, which can be biased, incomplete, or out-of-date. We extended Andrade and Valencia's method [1] to statistically mine functional keywords associated with genes from MEDLINE abstracts. The MEDLINE abstracts are analyzed statistically to score and rank keywords for each gene using a background set of words for baseline frequencies. We generally got very good functional keyword information about the genes we tested, which was confirmed by searching for the individual keywords in context. The keywords extracted by our algorithm reveal a wealth of potential functional concepts, which were not represented in existing public databases. We feel that this approach is general enough to apply to medical and biological literature to find other relationships: drugs vs. genes, risk-factors vs. genes, etc.

Algorithms↗

Altered histone acetylation at glutamate receptor 2 and brain-derived neurotrophic factor genes is an early event triggered by status epilepticus.

The mechanisms underlying seizure-induced changes in gene expression are unclear. Using a chromatin immunoprecipitation assay, we found that acetylation of histone H4 in rat hippocampal CA3 neurons was reduced at the glutamate receptor 2 (GluR2; GRIA2) glutamate receptor promoter but increased at brain-derived neurotrophic factor promoter P2 as soon as 3 hr after induction of status epilepticus by pilocarpine. This result indicates that status epilepticus rapidly activates different signal pathways to modulate histone acetylation in a promoter-specific manner. H4 deacetylation preceded seizure-induced GluR2 mRNA downregulation. The histone deacetylase inhibitor trichostatin A prevented and quickly reversed deacetylation of GluR2-associated histones. Trichostatin A also blunted seizure-induced downregulation of GluR2 mRNA in CA3. Thus, rapid gene-specific changes in histone acetylation patterns may be a key early step in the pathological processes triggered by status epilepticus.

Acetylation↗