Long-read DNA sequencing of Alzheimers Disease and Related Dementias cases

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

We have established a finalized brain-based DNA isolation protocol, and we have nearly completed the optimization of our blood sample DNA isolation protocol. We have begun to acquire blood, IPSC, and brain samples of interest with significant WGS, clinical, pathological, or omics data available. We have prioritized samples from underrepresented populations to better understand genetics of diverse populations. So far we have fully sequenced roughly 200 human frontal cortex brain samples with an average coverage of 30X and an average N50 of 30kb. We have identified platforms for digital storage and hosting of our long-read sequencing datasets. We have shared the current brain protocol on the widely-used and easily-accessible protocol sharing platform proticols.io (https://www.protocols.io/view/processing-human-frontal-cortex-brain-tissue-for-p-kxygxzmmov8j/v2/metrics) and this protocol has received over 1200 views. We will also establish and optimize pipelines and protocols for storing and processing long-read data. CARD Advanced Analytics has supported cloud based management and harmonization of data and analytics pipelines for long read sequencing of DNA, RNA and methylation. This team has also carried out benchmarking and pipeline refinements to maximize compute resources for CARD and its international collaborators. The Advanced Analytics team has also supported statistical analyses of structural variations.