Biology subjects

Wade, S.

Publications and source records attributed to Wade, S..

3 recordsLinked to original sources

bioRxiv2025

HBMAP: Bayesian inference of neural circuits from DNAbarcoded projection mapping

Decoding how the brain routes information through its precise, long-range wiring remains a central challenge in neuroscience. Barcode-based mapping of axonal projections allows brain-wide, high-throughput investigation of projections at single-neuron resolution offering a powerful solution. However, principled methods for statistical analysis of barcode count data that can detect common projection rules and effectively integrate datasets across subjects are lacking. To address these issues, we developed a model-based clustering approach through hierarchical Bayesian mixtures which we call hierarchical Bayesian mapping of axonal projections (HBMAP). We show that the inferred model accurately reflects the features of the data and allows simultaneous identification of projection patterns and characterization of uncertainty that accounts for subject variability. Our study presents the first Bayesian approach to barcode-based projection mapping, offering a general solution for this class of data.

neuroscience↗

bioRxiv2024

Quantifying uncertainty in RNA velocity

The concept of RNA velocity has made it possible to extract dynamic information from single-cell RNA sequencing data snapshots, attracting considerable attention and inspiring various extensions. Nonetheless, existing approaches lack uncertainty quantification and many adopt unrealistic assumptions or employ complex black-box models that are difficult to interpret. In this paper, we present a Bayesian hierarchical model to estimate RNA velocity, which leverages a time-dependent transcription rate and non-trivial initial conditions, allowing for well-calibrated uncertainty quantification. The proposed method is validated in a comprehensive simulation study that covers various scenarios, and benchmarked against a widely embraced and commonly recognized approach for RNA velocity on single-cell RNA sequencing data from mouse embryonic stem cells. We demonstrate that our model surpasses this widely used, state-of-the-art method, offering enhanced interpretation of cell velocity and cell orders. Additionally, it supports the estimation of a unified gene-shared latent time, providing a valuable resource for downstream analysis.

bioinformatics↗

bioRxiv2020

Strain-dependent modifier genes determine survival in Zfp423 mice

Zfp423 encodes a transcriptional regulatory protein that interacts with canonical signaling and lineage pathways. Mutations in mouse Zfp423 or its human ortholog ZNF423 are associated with a range of developmental abnormalities reminiscent of ciliopathies, including cerebellar vermis hypoplasia and other midline brain defects. Null mice have reduced viability in most strain backgrounds. Here we show complete lethality on a C57BL/6J background, dominant rescue in backcrosses to any of 13 partner strains, with strain-dependent survival frequencies, and evidence for a BALB/c-derived survival modifier locus on chromosome 5. Survival data indicate both perinatal and postnatal periods of lethality. Anatomical data from a hypomorphic gene trap allele observed on both C57BL/6J and BALB/c congenic backgrounds shows an aggregate effect of background on sensitivity to Zfp423 loss rather than a binary effect on viability.

genetics↗