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

• 批准号: 10468561
• 负责人: John Zhong
• 金额: $ 32.37万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 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/10468561
• 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; Chemoresistance; Chromosome abnormality; Clinical; Complementary DNA; Conduct Clinical Trials; Cytogenetic Analysis; Cytogenetics; Data; Data Set; Detection; Diagnosis; Diagnostic; Disease; Drug resistance; 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; Prognosis; Relapse; Reporting; Research Personnel; Resolution; 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 relapse; leukemia treatment; nanopore; new technology; next generation; risk stratification; single-cell RNA sequencing; survivin; therapeutic target; transcriptome sequencing; treatment response

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.

急性髓性白血病（AML）占所有成人白血病的32%， 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， 其具有低灵敏度和低分辨率的缺点。为了克服这一技术障碍， 我们建议使用单细胞RNAseq和微流体装置来产生分子 AML细胞遗传学谱的一个版本，包括来自大细胞的所有mRNA异常。 白血病细胞的数量，我们将这项技术命名为S-CytoSeq。这个分子S- CytoSeq分析提供融合基因（FG）和可变剪接（AS）谱， 单细胞分辨率，并将对AML治疗产生重大临床影响。的 最终的转化目标是用S-CytoSeq取代常规的细胞遗传学。