Jorge Lopez-Nava, a senior Mathematics student with minors in computer science and biology at Swarthmore College, used Single-cell ATAC-sequencing to build a pipeline and analyze the phenomenon of epigenetic erosion within neurons.
Transcription factors regulate transcription by cooperatively configuring chromatin loci to be either recalcitrant to or amenable to RNA polymerase engagement. The BSRP experience this summer was truly indescribable. The Broad allowed for exceptional academic growth with my research, in addition to a lot of personal growth with my cohort. This experience has given me life-long lessons and friendships that I’ll carry with me wherever I go.The current best approach for identifying and studying open chromatin regions in the genome at single cell resolution is Single-cell Assay of Transposase Accessible Chromatin sequencing (scATAC-seq). However, there is no current consensus on the best approach to analyze scATAC-seq data. Recently, studies have reported epigenetic erosion, where aging causes degradation of the epigenetic integrity of cells - this causes previously inaccessible regions to become accessible and vice versa. The goal of this project was to investigate how epigenetic erosion, responsible for changes for chromatin accessibility, can be modeled using epigenetic data from scATAC-seq data. Alignment was performed using an existing tool named Cell Ranger ATAC, a computational pipeline developed by 10xGenomics. Quality control and matrix formation were performed with AMULET and Bedops, respectfully. Using the outputed fragments file and reference ATACseq peak files, we analyzed a scATAC-seq dataset of the prefrontal cortex in the human brain with designed metrics. Chromatin accessibility was found to change over the course of aging, and epigenetic erosion was more prevalent in samples with neurodegenerative diseases. The transcription factor footprints were identified in the scATAC-seq dataset. Our approach therefore has potential for uncovering de-noised causes and solutions for the effects of epigenetic erosion. Future models will integrate scATAC-seq analysis with that of scRNA-seq to induce target epigenetic and transcriptional phenotypes.
Project: Estimating Chromatin Accessibility and Epigenetic Erosion from Single-cell ATAC-seq
Mentors: Alex Lenail, Manolis Kellis