Biology subjects

Adey, A. C.

Publications and source records attributed to Adey, A. C..

3 recordsLinked to original sources

bioRxiv2018

The accessible chromatin landscape of the hippocampus at single-cell resolution

Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution. Substantial advances of this work include the optimization of single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq), a software suite, scitools, for the rapid processing and visualization of single-cell combinatorial indexing datasets, and a valuable resource of hippocampal regulatory networks at single-cell resolution. We utilized sci-ATAC-seq to produce 2,346 high-quality single-cell chromatin accessibility maps with a mean unique read count per cell of 29,201 from both fresh and frozen hippocampi, observing little difference in accessibility patterns between the preparations. Using this dataset, we identified eight distinct major clusters of cells representing both neuronal and non-neuronal cell types and characterized the driving regulatory factors and differentially accessible loci that define each cluster. We then applied a recently described co-accessibility framework, Cicero, which identified 146,818 links between promoters and putative distal regulatory DNA. Identified co-accessibility networks showed cell-type specificity, shedding light on key dynamic loci that reconfigure to specify hippocampal cell lineages. Lastly, we carried out an additional sci-ATAC-seq preparation from cultured hippocampal neurons (899 high-quality cells, 43,532 mean unique reads) that revealed substantial alterations in their epigenetic landscape compared to nuclei from hippocampal tissue. This dataset and accompanying analysis tools provide a new resource that can guide subsequent studies of the hippocampus.

neuroscience↗

bioRxiv2018

High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice

We developed \"sci-LIANTI\", a high-throughput, high-coverage single-cell DNA sequencing method that combines single-cell combinatorial indexing (\"sci\") and linear amplification via transposon insertion (\"LIANTI\"). To characterize rare chromosome mis-segregation events in male meiosis and their relationship to the landscape of meiotic crossovers, we applied sci-LIANTI to profile the genomes of 6,928 sperm and sperm precursors from infertile, interspecific F1 male mice. From 1,663 haploid and 292 diploid cells, we mapped 24,672 crossover events and identified genomic and epigenomic contexts that influence crossover hotness. Surprisingly, we observed frequent mitotic chromosome segregation during meiosis. Moreover, segregation during meiosis in individual cells was highly biased towards either mitotic or meiotic events. We anticipate that sci-LIANTI can be applied to fully characterize various recombination landscapes, as well as to other fields requiring high-throughput, high-coverage single-cell genome sequencing.\n\nOne Sentence SummarySingle-cell genome sequencing maps crossover and non-meiotic chromosome segregation during spermatogenesis in interspecific hybrid mice.

genetics↗

bioRxiv2017

Scalable and efficient single-cell DNA methylation sequencing by combinatorial indexing.

Here we present a novel method: single-cell combinatorial indexing for methylation analysis (sci-MET), which is the first highly scalable assay for whole genome methylation profiling of single cells. We use sci-MET to produce 2,697 total single-cell bisulfite sequencing libraries and achieve read alignment rates of 69 {+/-} 7%, comparable to those of bulk cell methods. As a proof of concept, we applied sci-MET to successfully deconvolve the cellular identity of a mixture of three human cell lines.

genomics↗