Search bioRxiv⌕ Search

Biology subjects

Zemke, N.

Publications and source records attributed to Zemke, N..

2 recordsLinked to original sources

SnapATAC2: a fast, scalable and versatile tool for single-cell omics analysis

Single-cell omics technologies have ushered in a new era for the study of dynamic gene regulation in complex tissues during development and disease pathogenesis. A major computational challenge in analyzing these datasets is to project the large-scale and high dimensional data into low-dimensional space while retaining the relative relationships between cells in order to decompose the cellular heterogeneity and reconstruct cell-type-specific gene regulatory programs. Conventional dimensionality reduction methods suffer from computational inefficiency, difficulty to capture the full spectrum of cellular heterogeneity, or inability to apply across diverse molecular modalities. Here, we report a fast and nonlinear dimensionality reduction algorithm that not only more accurately captures the heterogeneities of single-cell omics data, but also features runtime and memory usage that is computational efficient and linearly proportional to cell numbers. We implement this algorithm in a Python package named SnapATAC2, and demonstrate its superior performance, remarkable scalability and general adaptability using an array of single-cell omics data types, including single-cell ATAC-seq, single-cell RNA-seq, single-cell Hi-C, and single-cell multiomics datasets.

genomics↗

A comparative atlas of single-cell chromatin accessibility in the human brain

The human brain contains an extraordinarily diverse set of neuronal and glial cell types. Recent advances in single cell transcriptomics have begun to delineate the cellular heterogeneity in different brain regions, but the transcriptional regulatory programs responsible for the identity and function of each brain cell type remain to be defined. Here, we carried out single nucleus ATAC-seq analysis to probe the open chromatin landscape from over 1.1 million cells in 42 brain regions of three neurotypical adult donors. Integrative analysis of the resulting data identified 107 distinct cell types and revealed the cell-type-specific usage of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly 1/3 of them displayed sequence conservation as well as chromatin accessibility in the mouse brain. On the other hand, nearly 40% cCREs were human specific, with chromatin accessibility associated with species-restricted gene expression. Interestingly, these human specific cCREs were enriched for distinct families of retrotransposable elements, which displayed cell-type-specific chromatin accessibility. We uncovered strong associations between specific brain cell types and neuropsychiatric disorders. We futher developed deep learning models to predict regulatory function of non-coding disease risk variants.

neuroscience↗