I hope everyone who came along to the BRC symposium on mining EHRs yesterday had an enjoyable and productive afternoon. Thanks to all of the speakers for some fantastic talks.
I will upload the presentations to the website over the next few days so please keep an eye on the event page if you would like copies.
Lunnon K, Ibrahim Z, Proitsi P, Lourdusamy A, Newhouse S, Sattlecker M, Furney S, Saleem M, Soininen H, Kłoszewska I, Mecocci P, Tsolaki M, Vellas B, Coppola G, Geschwind D, Simmons A, Lovestone S, Dobson R, Hodges A.
J Alzheimers Dis. 2012 Jan 1;30(3):685-710.
Alzheimer’s disease (AD), like other dementias, is characterized by progressive neuronal loss and neuroinflammation in the brain. The peripheral leukocyte response occurring alongside these brain changes has not been extensively studied, but might inform therapeutic approaches and provide relevant disease biomarkers. Using microarrays, we assessed blood gene expression alterations occurring in people with AD and those with mild cognitive changes at increased risk of developing AD. Of the 2,908 differentially expressed probes identified between the three groups (p < 0.01), a quarter were altered in blood from mild cognitive impairment (MCI) and AD subjects, relative to controls, suggesting a peripheral response to pathology may occur very early. There was strong evidence for mitochondrial dysfunction with decreased expression of many of the respiratory complex I-V genes and subunits of the core mitochondrial ribosome complex. This mirrors changes previously observed in AD brain. A number of genes encoding cell adhesion molecules were increased, along with other immune-related genes. These changes are consistent with leukocyte activation and their increased the transition from circulation into the brain. In addition to expression changes, we also found increased numbers of basophils in people with MCI and AD, and increased monocytes in people with an AD diagnosis. Taken together this study provides both an insight into the functional response of circulating leukocytes during neurodegeneration and also identifies potential targets such as the respiratory chain for designing and monitoring future therapeutic interventions using blood.
The Brain & Body Genetic Resource Exchange (BB-GRE) provides a resource for investigating the genetic basis of neurodisability. It combines phenotype information from patients with neurodevelopmental and behavioural problems with clinical genetic data, and displays this information on the human genome map.
Primer Designer was written to automate the Buckley Lab primer design process. It is essentially just a wrapper around Primer3 with extra modules to pull sequence data from Ensembl and to check secondary structure formation with Unafold.
Code for Primer Designer is on Github, feel free to fork.
Dr. Richard Dobson will be speaking at the King’s Health Partners Grand Challenge Conference on Tuesday 3rd July, outlining plans to build on current informatics successes to address the challenges that will be faced by KHP in the era of personalised medicine.