Broadly Accessible Technologies for Single-cell Joint Analysis of Transcriptome and Epigenome

AbstractHistone modifications carry rich information of cellular memory and gene regulatory mechanisms. Single cell
analysis of histone modification in conjunction with transcriptome could recover this critical layer of cell identity
and help to dissect the cellular and molecular composition of complex tissues such as the brain. We recently
developed an ultra-high throughput single cell multi-omics assay, Paired-Tag, that can jointly map transcriptome
and histone modifications from up to a million single cells in parallel. In order to translate this novel technology
to the marketplace and to advance the goals of the BRAIN initiative, we propose to optimize and further develop
Paired-Tag to enable its broad use in the research community. Specifically, we will develop Paired-Tag kits to
allow for general accessibility of the method in molecular biology laboratories. We will then carry out extensive
field tests of the Paired-Tag kit in the laboratories of current BRAIN initiative investigators, and further improve it
based on the feedbacks. Finally, we will adapt the Paired-Tag procedure to long-read sequencing technologies
to enable high throughput detection of splicing isoforms in brain cells at single cell resolution. If successful, the
proposed research would provide researchers with a powerful new tool for single cell transcriptomics and
epigenomics analysis.We proposed to translate a novel technology supported by Brain Research through Advancing Innovative
Neurotechnologies (BRAIN)-initiative to the marketplace, to help investigators to better map the inner workings
of brain cells at single cell resolution and dissect the organization and function of the neural circuits.