Lyra Sheu

Single-cell atlas of transcriptomic vulnerability across brain disorders

Abstract Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited 1,2 . Here, to gain deeper insights into the aetiolo...

Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer’s disease

Alzheimer’s disease (AD) is highly heterogeneous and driven by diverse molecular and cellular mechanisms. Functional genomics investigates these mechanisms from genetic variants to gene expression and regulation. We performed personalized functional genomics analysis on populatio...

Single-nucleus atlas of cell-type specific genetic regulation in the human brain

Abstract Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of th...

AI-based characterization of Alzheimer’s disease phenotypes from population-scale single-cell data

The complexity of Alzheimer’s disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms. However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-n...

Single-nucleus transcriptome-wide association study of human brain disorders

Abstract Common brain disorders impose a substantial health burden, but localizing their genetic risk in the brain remains challenging 1 . Although genome-wide association studies have identified numerous loci associated with neuropsychiatric and neurodegenerative disorders, many...

Lifespan single-cell transcriptomic atlas of the human prefrontal cortex

The human brain undergoes profound changes from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease1,2. Understanding how these changes are organized within specific brain regions and cell types is essential for interpreting normal...