Computational Methods for Inferring Single-cell DNA Methylation and its Spatial Landscape

推断单细胞 DNA 甲基化及其空间景观的计算方法

基本信息

批准号：
10679088
负责人：
Wenpin Hou
金额：
$ 24.9万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10679088
关键词：
3-Dimensional Accounting Address Aging Atlases Award Biometry Calibration Cells Chromatin Clinical Trials Code Collaborations Communities Computing Methodologies CpG dinucleotide DNA DNA Methylation DNA Methyltransferase Inhibitor DNA Sequence DNA analysis Data Data Set Development Developmental Process Disease Doctor of Philosophy Early Diagnosis Emerging Technologies Encyclopedia of DNA Elements Engineering Epigenetic Process Evaluation Funding Gene Expression Gene Expression Regulation Genes Genetic Transcription Genomic Segment Genomics Goals Hong Kong Human Immune checkpoint inhibitor Immune response Joints Link Location Malignant Neoplasms Mammals Mathematics Measurement Measures Medicine Mentors Methodology Methods Methylation Modeling Multiomic Data Mutation Outcome Patients Pharmaceutical Preparations Phase Phenotype Population Population Heterogeneity Postdoctoral Fellow Prediction of Response to Therapy Productivity Prognosis Promoter Regions Proteins Protocols documentation Public Health Schools Regulation Regulator Genes Research Research Personnel Resolution Resources Sample Size Sampling Series Signal Transduction Site Statistical Methods System Techniques Technology Therapeutic Tissues Training United States National Institutes of Health Universities Variant Work career career development cell type clinical practice clinical translation computing resources deep learning deep learning model developmental disease disease classification disorder prevention epigenome epigenomics experimental study gene regulatory network gene repression genomic data improved insight interest multimodal data novel programs reference genome single-cell RNA sequencing statistics targeted treatment therapeutic target tool transcriptome sequencing transcriptomics

项目摘要

Project Summary/Abstract The candidate, Wenpin Hou, PhD, is an applied mathematician and computational biologist serving as a postdoctoral fellow of Biostatistics at Johns Hopkins Bloomberg School of Public Health (JHSPH). Her long-term career goal is to improve clinical practice in therapy for diseases by developing computational and statistical methods to decipher spatial and temporal gene regulatory programs using multi-omics data and implementing these methods into developmental process and diseases. The research she proposes entitled Computational Methods for Inferring Single-cell DNA Methylation and its Spatial Landscape combines advanced spatial transcriptomics techniques with computational methods to infer spatial DNA methylation landscape, which enables the accurate evaluation of the epigenomic spatial variability and epigenomic targets in therapy for diseases. Dr. Hou completed her PhD in Mathematics at The University of Hong Kong where she focused on inferring and controlling gene regulatory networks (GRNs). Her ﬁrst postdoctoral research (2017-2019) with Drs. Aravinda Chakravarti and Suchi Saria at Johns Hopkins University (JHU) represented the ﬁrst shift in focus of GRNs from theoretical to computational genomics. Her second postdoctoral research (2019-present) with Drs. Hongkai Ji and Stephanie Hicks at JHSPH has further provided complementary training in reconstructing and predicting spatial transcriptomic and epigenomic landscape using single-cell data. Dr. Hou's mentoring team consists of Hongkai Ji (primary mentor), PhD, an expert in developing computational and statistical tools for analyzing single-cell genomic data, including reconstructing and predicting temporal and spatial transcriptomic and epigenomic landscape; Stephanie Hicks (co-mentor), PhD, an expert in developing statistical methods to address technical variability and spatial transcriptomics in single cells; and Andrew Feinberg (co-mentor), PhD, one of the founders of the ﬁeld of cancer epigenetics who directs the ﬁrst NIH funded Epigenome Center. This offers the opportunity to tackle signiﬁcant challenges in the intersection of statistics, epigenomics and spatial transcriptomics with advanced experimental techniques. Her scientiﬁc advisors are Drs. Kasper Hansen, Gregory Hager and Xiaobin Wang who have leading expertise in computational epigenomics, deep learning, clinical translation and disease prevention, respectively. Leveraging the intellectual, experimental, and computing resources from all mentors and advisors as well as through JHSPH, JHU and Johns Hopkins Medicine, Dr. Hou will receive intensive training, mentoring and career development to achieve the goals proposed in this application and have productive outcomes during the award period. Aim 1 will develop methods to predict DNA methylation landscape using bulk gene expression. Aim 2 will develop methods to predict single-cell DNA methylation and differential DNA methylation. Aim 3 will reconstruct tissue-spatial DNA methylation landscape at the single-cell level, generate evaluation datasets in spatial context, and perform across-study assessments using data from The Encyclopedia of DNA Elements (ENCODE), Human Cell Atlas, and Recount2.

项目概要/摘要候选人侯文品博士是一位应用数学家和计算生物学家，担任约翰·霍普金斯大学彭博公共卫生学院 (JHSPH) 生物统计学博士后研究员。职业目标是通过开发计算和统计来改善疾病治疗的临床实践使用多组学数据破译空间和时间基因调控程序的方法并实施该研究提出了题为“计算”的研究方法。推断单细胞 DNA 甲基化及其空间景观的方法结合了先进的空间转录组学技术与计算方法推断空间 DNA 甲基化景观，能够准确评估治疗中的表观基因组空间变异性和表观基因组目标侯博士在香港大学完成了数学博士学位，她的研究方向是疾病。她的第一个博士后研究（2017-2019）与博士一起推断和控制基因调控网络（GRN）。约翰·霍普金斯大学 (JHU) 的 Aravinda Chakravarti 和 Suchi Saria 代表了研究焦点的首次转变她的第二次博士后研究（2019 年至今），从理论到计算基因组学。 JHSPH 的 Hongkai Ji 和 Stephanie Hicks 进一步提供了重建和恢复方面的补充培训。使用单细胞数据预测空间转录组和表观基因组景观。由洪凯吉（主要导师）博士组成，他是开发计算和统计工具的专家分析单细胞基因组数据，包括重建和预测时间和空间转录组和表观基因组景观；Stephanie Hicks（共同导师）博士，开发统计方法的专家解决单细胞的技术变异性和空间转录组学问题；Andrew Feinberg（共同导师）博士，癌症表观遗传学领域的创始人之一，领导着第一个 NIH 资助的表观基因组中心。提供了解决统计学、表观基因组学和空间交叉领域重大挑战的机会她的科学顾问是 Kasper Hansen 博士。 Gregory Hager 和王晓斌在计算表观基因组学、深度学习、分别利用智力、实验和计算。来自所有导师和顾问以及 JHSPH、JHU 和约翰霍普金斯医学院的资源，Hou 博士将接受强化培训、指导和职业发展，以实现本报告中提出的目标目标 1 将开发预测 DNA 的方法。使用大量基因表达的甲基化景观将开发预测单细胞 DNA 的方法。目标 3 将重建组织空间 DNA 甲基化景观。单细胞水平，生成空间背景下的评估数据集，并进行跨研究评估使用来自 DNA 元素百科全书 (ENCODE)、人类细胞图谱和 Recount2 的数据。