权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Accessible high-throughput single-cell genome sequencing

可获得的高通量单细胞基因组测序

基本信息

批准号：
10612457
负责人：
Andrew Adey
金额：
$ 37.3万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
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：
2022-04-21 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612457
关键词：
ATAC-seq Acoustics Area Atlases Bar Codes Basic Science Benchmarking Biological Assay Cancer Biology Catalogs Cell Line Cell Nucleus Cells Chemistry Chromium Clinical Collaborations Communities Complex Computer software Cost Effectiveness Analysis Cost Savings Custom DNA Sequence Rearrangement Data Detection Evolution Genes Genetic Genome Genomics High-Throughput Nucleotide Sequencing Human Hybrids In Situ Libraries Liquid substance Metastatic breast cancer Methodology Methods Microfluidics Mus Nucleosomes Pancreatic Ductal Adenocarcinoma Point Mutation Population Primary Brain Neoplasms Property Protocols documentation Publishing Reagent Reproducibility Research Resistance Sampling Single Nucleotide Polymorphism Solid Neoplasm Structure Technology Therapeutic Validation analysis pipeline anticancer research cost cost effective density design exome exome sequencing experimental study gene panel genome sequencing genomic profiles improved in situ sequencing indexing instrument instrumentation interest nano novel single cell sequencing therapy resistant tool tumor tumor initiation tumor progression variant detection whole genome

项目摘要

PROJECT SUMMARY Initiation and evolution of most solid tumors involve complex genomic rearrangements in addition to point mutations – all of which can contribute to cancer progression and to the evolution of resistance to therapeutics. Single-cell whole genome sequencing (scWGS) has proven invaluable for the identification of tumor subpopulations and in advancing our understanding of clonal dynamics and tumor evolution. Despite the value of scWGS, there is a dearth of commercially-available options that provide enough cell throughput (i.e. power) and/or genomic coverage to fully catalogue and characterize clonal populations within a tumor sample. This can be particularly problematic when rare, possible therapy-resistant, subpopulations are present within a tumor that may elude detection using existing methodologies. Here we will solve the accessibility problem by developing technologies that leverage widely-available instrumentation and off-the-shelf reagents. We previously described proof-of-principle technologies to construct scWGS libraries contained within the nucleus (in situ) of each cell that are then carried through cell barcoding using our custom workflow. We will extend, develop, and adapt these technologies to provide three workflows that will meet the needs of the cancer research community by providing readily-accessible order-of-magnitude improvements to cell throughput, cell coverage and cost savings for scWGS analysis over current options. The first is focused on high cell throughput using widely available instrumentation; the second leverages our high- content chemistry to produce high-coverage single cell genomic profiles with reduced reagents and improved throughput; and finally, the third approach implements target capture to target exonic sequence or other regions of interest to reduce sequencing costs. Each of these is targeted to meet the needs of specific areas of cancer research, from basic science to clinical, and share the theme of accessibility.

项目总结