CHAS

CHAS infers cell type-specific signatures in bulk brain histone acetylation studies to identify biological pathways associated with neurological and psychiatric disorders at cellular resolution.

Key Features:

• Cell type-specific inference: CHAS infers cell type-specific signatures from bulk brain H3K27ac chromatin immunoprecipitation sequencing profiles.
• Disease recapitulation: CHAS recapitulates known disease-associated shifts in cellular proportions across multiple brain disorders.
• Cell type-specific biological insights: CHAS identifies cell type-specific biological insights into brain-disorder-associated regulatory variation.
• Genetic and epigenetic mechanism dissection: CHAS distinguishes whether genetic risk and epigenetic dysregulation target the same or different cell types, revealing independent mechanisms.
• Pathway identification at cellular resolution: CHAS enables identification of biological pathways associated with neurological and psychiatric disorders at cellular resolution.

Scientific Applications:

• Alzheimer's disease: CHAS identified that genetic risk of Alzheimer's disease was exclusively enriched within microglia, while epigenetic dysregulation predominantly fell within oligodendrocyte-specific H3K27ac regions.
• Parkinson's disease: CHAS was applied to H3K27ac chromatin immunoprecipitation sequencing samples from Parkinson's disease studies in bulk postmortem brain tissue.
• Autism spectrum disorder: CHAS was applied to H3K27ac chromatin immunoprecipitation sequencing samples from autism spectrum disorder studies in bulk postmortem brain tissue.
• Schizophrenia: CHAS was applied to H3K27ac chromatin immunoprecipitation sequencing samples from schizophrenia studies in bulk postmortem brain tissue.
• Bipolar disorder: CHAS was applied to H3K27ac chromatin immunoprecipitation sequencing samples from bipolar disorder studies in bulk postmortem brain tissue.

Methodology:

CHAS is implemented as an R package and computes cell type-specific histone acetylation scores from bulk brain H3K27ac profiles.