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Infernape uncovers cell type--specific and spatially resolved alternative polyadenylation in the brain

Differential polyadenylation sites (PAs) critically regulate gene expression, but their cell type–specific usage and spatial distribution in the brain have not been systematically characterized. Here, we present Infernape, which infers and quantifies …

Detecting Multiple Replicating Signals using Adaptive Filtering Procedures

Replicability is a fundamental quality of scientific discoveries: we are interested in those signals that are detectable in different laboratories, different populations, across time etc. Unlike meta-analysis which accounts for experimental …

Causal Inference for Heritable Phenotypic Risk Factors Using Heterogeneous Genetic Instruments

A Mendelian randomization study of the role of lipoprotein subfractions in coronary artery disease

Recent genetic data can offer important insights into the roles of lipoprotein subfractions and particle sizes in preventing coronary artery disease (CAD), as previous observational studies have often reported conflicting results. We used the LD …

Progenitor cell diversity in the developing mouse neocortex

In the mammalian neocortex, projection neuron types are sequentially generated by the same pool of neural progenitors. How neuron type specification is related to developmental timing remains unclear. To determine whether temporal gene expression in …

Data Denoising and Post-Denoising Corrections in Single Cell RNA Sequencing

Single cell sequencing technologies are transforming biomedical research. However, due to the inherent nature of the data, single cell RNA sequencing analysis poses new computational and statistical challenges. We begin with a survey of a selection …

Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score

Mendelian randomization (MR) is a method of exploiting genetic variation to unbiasedly estimate a causal effect in presence of unmeasured confounding. MR is being widely used in epidemiology and other related areas of population science. In this …

Surface protein imputation from single cell transcriptomes by deep neural networks

While single cell RNA sequencing (scRNA-seq) is invaluable for studying cell populations, cell-surface proteins are often integral markers of cellular function and serve as primary targets for therapeutic intervention. Here we propose a transfer …

Powerful genome-wide design and robust statistical inference in two-sample summary-data Mendelian randomization

We develop an empirical partially Bayes statistical analysis approach where instruments are weighted according to their strength; thus weak instruments bring less variation to the estimator. The estimator is highly efficient with many weak genetic …

Admissibility in Partial Conjunction Testing

Meta-analysis combines results from multiple studies aiming to increase power in finding their common effect. It would typically reject the null hypothesis of no effect if any one of the studies shows strong significance. The partial conjunction null …