Large scale single-cell gene rearrangement detection with a microfluidic device

利用微流控装置进行大规模单细胞基因重排检测

基本信息

批准号：
10031278
负责人：
John Zhong
金额：
$ 37.74万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10031278
关键词：
Acute Myelocytic Leukemia Adult Acute Myeloblastic Leukemia Alternative Splicing Antibodies Benchmarking Biological Assay Bone Marrow Cell Line Cell fusion Cells Cessation of life Chromosome abnormality Clinical Complementary DNA Conduct Clinical Trials Cytogenetic Analysis Cytogenetics Data Data Set Detection Diagnosis Diagnostic Disease Drug resistance Expression Profiling Flow Cytometry Gene Expression Gene Rearrangement Genetic Genomics Goals Length Leukemic Cell Malignant Neoplasms Measures Messenger RNA Metaphase Microfluidic Microchips Microfluidics Molecular Names Outcome Patients Pharmaceutical Preparations Play Relapse Reporting Research Personnel Resolution Risk stratification Role Sampling Selection for Treatments Sensitivity and Specificity Spliced Genes Survival Rate Techniques Technology acute myeloid leukemia cell adult leukemia base bioinformatics pipeline chemotherapy computational pipelines droplet sequencing drug relapse fusion gene improved leukemia treatment nanopore new technology next generation outcome forecast single-cell RNA sequencing survivin therapeutic target transcriptome sequencing treatment response

项目摘要

Acute myeloid leukemia (AML) contributes to 32% of all adult leukemia and remains one of the most clinically devastating cancers. Currently, AML diagnosis, risk stratification and treatment selection are mainly based on cytogenetic abnormalities, which suffers from low sensitivity and low resolution. To overcome this technical hurdle, we propose to use single-cell RNAseq with microfluidic devices to generate a molecular version of AML cytogenetic profile including all mRNA abnormalities from a large number of leukemia cells, a technique we have named S-CytoSeq. This molecular S- CytoSeq profiling provides fusion genes (FG) and alternative splicing (AS) profiles at single-cell resolution and will have a significant clinical impact on AML treatment. The ultimate translational goal is to replace conventional cytogenetics with S-CytoSeq.

急性髓样白血病（AML）占所有成人白血病的32％和仍然是临床上最具破坏性的癌症之一。目前，AML诊断，风险分层和治疗选择主要基于细胞遗传学异常，遭受低灵敏度和低分辨率的遭受。为了克服这一技术障碍，我们建议将单细胞RNASEQ与微流体设备一起产生分子 AML细胞遗传学曲线的版本，包括来自大的所有mRNA异常白血病细胞的数量，我们称为S-Cytoseq的技术。这个分子s- Cytoseq分析提供融合基因（FG）和替代剪接（AS）剖面单细胞分辨率，将对AML治疗产生重大临床影响。这最终的翻译目标是用S-Cytoseq替换常规的细胞遗传学。