Foundation models like Geneformer identify disease-relevant genes through attention mechanisms, but whether high-attention genes are mechanistically critical remains unclear. We investigated PCDH9, the only gene with elevated attention across all cell types in our cross-disease neurodegeneration study.
Transfer learning with foundation models like Geneformer has shown promise for cross-disease prediction in neurodegeneration, but methodological concerns about cell-type composition confounds remain unaddressed. We conducted cell-type stratified experiments across Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), fine-tuning Geneformer within four homogeneous cell populations.
Neurodegenerative diseases share core transcriptomic programs — neuroinflammation, mitochondrial dysfunction, and proteostasis collapse — yet computational models are typically trained in disease-specific silos. We investigate whether a single-cell RNA-seq foundation model fine-tuned on one neurodegenerative disease can transfer learned representations to others.
Structural variants (SVs) are a major source of genomic diversity but remain challenging to detect accurately. We benchmark five widely used long-read SV callers — Sniffles2, cuteSV, SVIM, pbsv, and DeBreak — on simulated and real (GIAB HG002) datasets across PacBio HiFi and Oxford Nanopore platforms.