Arrayed CRISPR libraries extend the scope of gene-perturbation screens to non-selectable cell phenotypes. However, library generation requires assembling thousands of vectors expressing single-guide RNAs (sgRNAs). Here, by leveraging massively parallel plasmid-cloning methodology, we show that arrayed libraries can be constructed for the genome-wide ablation (19,936 plasmids) of human protein-coding genes and for their activation and epigenetic silencing (22,442 plasmids), with each plasmid encoding an array of four non-overlapping sgRNAs designed to tolerate most human DNA polymorphisms.
View Article and Find Full Text PDFBackground: Magnetic resonance imaging (MRI) has recently enabled to identify four distinct Alzheimer's disease (AD) subtypes: hippocampal sparing (HpSp), typical AD (tAD), limbic predominant (Lp), and minimal atrophy (MinAtr). To date, however, the natural history of these subtypes, especially regarding the presence of subjects switching to other MRI patterns and their clinical and biological differences, remains poorly understood.
Objective: To investigate the clinical and biological underpinnings of longitudinal atrophy pattern progression in AD.