Human Bone Marrow ATAC-seq Atlas: Mapping Chromatin Accessibility through Transposase-Accessible Chromatin Sequencing

  • Mashael F. Alghuraybi

Student thesis: Master's Thesis


The bone marrow (BM) is a crucial tissue involved in hematopoiesis and immune cell development. The construction of a comprehensive bone marrow atlas is essential to understand the regulatory mechanisms and functional characteristics of different cell types. My thesis is a contribution to a larger effort aimed at the generation of a Bone Marrow Atlas, with a special interest in non-hematopoietic cells. My contribution fo-cuses in the chromatin accessibility part based on Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data, therefore offering valuable insights into chromatin accessibility and gene regulation by transcription factors (TFs). The work developed in the thesis can be divided in three parts: (i) identification of da-tasets of interest (data collection); (ii) processing the data: implementation of ATAC-seq pipeline, and (iii) a proof-of-concept on how to make sure of this data collection in research: a Shiny application and a use case. The data collection included in the atlas have both in-house and publicly available ATAC-seq human paired data encompassing various cell types. ATAC-seq pipeline was imple-mented to process and analyze bone marrow samples, facilitating the identification of cell type-specific accessible chromatin regions. This analysis is composed by several es-sential steps to extract valuable information about chromatin accessibility and regulato-ry elements. These steps involve the preprocessing of raw sequencing data, alignment to a reference genome (hg38), peak calling to detect open chromatin regions (OCRs), and downstream analysis to associate TFs with the identified peaks. The BM atlas incorporates the ATAC-seq data generated through this pipeline along with gene expression profiles produced from RNA-seq another project as part of the BM atlas. The combination of these techniques offers a comprehensive understanding of the bone marrow's molecular landscape and uncover the interplay between chromatin accessibility and gene expression. To facilitate a user-friendly exploration of the BM atlas, we have developed an interac-tive R Shiny app. This app empowers researchers to navigate the atlas, visualize gene expression patterns, and investigate regulatory networks associated with bone marrow cell types. It serves as a powerful tool to unravel the intricate interplay between chro-matin accessibility, gene regulation, and TFs within the bone marrow context. Addition-ally, we created a user case study focusing on H1 linker histones, demonstrating their impact on chromatin accessibility, gene expression, and cell fate decisions across di-verse bone marrow cell types. This case study highlights the utility of the BM atlas in uncovering the role of specific epigenetic regulators in this tissue.
Date of AwardJun 2023
Original languageEnglish (US)
Awarding Institution
  • Biological, Environmental Sciences and Engineering

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