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Area A: High Precision Single Cell Genomes: Linear Amplification and Digital Haplotypes

A 区：高精度单细胞基因组：线性扩增和数字单倍型

基本信息

批准号：
9483092
负责人：
XIAOLIANG SUNNEY XIE
金额：
$ 170.89万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-30 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9483092
关键词：
Algorithm Design Area Benchmarking Benign Bioinformatics Breast Cancer cell line Cancer cell line Cell Cycle Cells Cellular biology Chromosomal Rearrangement Chromosomes Companions Computing Methodologies Consensus DNA DNA copy number Dana-Farber Cancer Institute Data Data Analyses Databases Daughter Detection Development Diploidy Drug resistance Experimental Models Generations Genetic Genetic Heterogeneity Genetic Transcription Genetic Variation Genome Genomic DNA Genomics Goals Haplotypes Human Immune system In Vitro Label Laboratories Libraries Malignant Neoplasms Methods Mutagenesis Nature Neoplasm Circulating Cells Neoplasm Metastasis Nucleotides Performance Phase Point Mutation RNA Research S-Phase Fraction Sampling Siblings Sister Chromatid Site Somatic Cell System Technology Time Tn5 transposase Validation Variant anticancer research base cancer cell cancer genome cancer heterogeneity computerized data processing digital experimental study genome analysis genome sequencing genomic profiles live cell imaging neoplastic cell novel strategies promoter single cell analysis single cell sequencing success therapy resistant tool translational cancer research tumor tumor heterogeneity tumorigenesis whole genome

项目摘要

Project Summary/Abstract This proposal brings together four research teams with expertise in cancer genome sequencing, single-cell sequencing, and cancer cell biology to advance single-cell sequencing technology to tackle compelling questions in basic and translational cancer research. It responds to RFA-CA-17-023, Cancer Moonshot Initiative, and proposes to create and validate a platform of experimental and analytical approaches for precise single-cell sequencing of human samples based on the most recent advance in single-cell whole-genome amplification, Linear Amplification after Transposon Insertion (LIANTI), developed by the Xie laboratory. The immediate goal is to further develop LIANTI and augment bioinformatic analysis for single-cell LIANTI sequencing. Aim 1 focuses on developing a high throughput version of LIANTI. Aim 2 focuses on developing computational methods that utilize the digital and linear nature of LIANTI sequencing data. Aim 3 describes strategies and experimental models that will be used to validate and benchmark single-cell LIANTI sequencing performance and demonstrate its applicability to tumor analysis. Overall, our goal is to optimize and implement the most precise single-cell sequencing technology for variant detection in single cancer or somatic cells. Success of the project will result in an integrated platform that overcomes prevailing impediments in single-cell analysis and can have a transformative impact in multiple areas of cancer research, including tumor genetic heterogeneity, circulating tumor cells, primary/metastasis relationship, drug resistance, and benign-to- malignancy transformation.

项目总结/摘要这项提议汇集了四个研究团队，他们在癌症基因组测序、单细胞肺癌和癌症研究方面具有专业知识。测序和癌细胞生物学，以推进单克隆细胞测序技术，基础和转化癌症研究中的问题。它回应了RFA-CACA-2017 - 2023，癌症登月计划倡议，并建议建立和验证一个实验和分析方法的平台，基于单细胞全基因组最新进展的人类样本单细胞测序转座子插入后的线性扩增（LIANTI），由Xie实验室开发。近期目标是进一步开发LIANTI，并增强单细胞LIANTI的生物信息学分析目标1专注于开发LIANTI的高通量版本。目标2专注于开发LIANTI的高通量版本。利用LIANTI测序数据的数字和线性性质的计算方法。将用于验证和基准单细胞LIANTI测序的策略和实验模型性能，并证明其适用于肿瘤分析。总的来说，我们的目标是优化和实施最精确的单细胞测序技术，用于单个癌症或体细胞中的变异检测。该项目的成功将产生一个综合平台，克服单一电池的普遍障碍分析，并可能在癌症研究的多个领域产生变革性影响，包括肿瘤遗传学异质性、循环肿瘤细胞、原发/转移关系、耐药性和良性肿瘤恶性转化