BIOINFORMATICS: SYSTEMS BIOLOGY OF NEUROBLASTOMA

生物信息学：神经母细胞瘤的系统生物学

• 批准号: 8349272
• 负责人: Javed Khan
• 金额: $ 11.63万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349272
• 关键词: Age; Amino Acid Sequence; Bioinformatics; Biological; Biology; Cells; Clinical; Complex; DNA; DNA copy number; Genes; Genetic Transcription; Genome; Genomics; Individual; Investigation; Lead; Malignant Neoplasms; Messenger RNA; Methylation; MicroRNAs; Modeling; Morbidity - disease rate; Neuroblastoma; Outcome; Pathway interactions; Patients; Pattern; Peptide Sequence Determination; Phenotype; Proteins; Proteome; Proteomics; Staging; System; Systems Biology; biological systems; cancer cell; cell growth; genome-wide; high risk; improved; mathematical model; protein expression; protein profiling

It has become increasingly clear that individual genes do not act in isolation within a cell, but acts in concert with other genes within pathways. In addition, many genes within a pathway are redundant such that many genes can perform a particular function, and conversely a single gene can have many functions depending on its cellular context. High throughput genome wide approaches allow the investigation of the complexity of cell as a whole. The integration of genomics and proteomics with functional analysis will be referred to as systems biology. My lab has utilized these systematic approaches to understand more clearly the biology of high-risk neuroblastoma. Systems biology seeks to integrate high-throughput biological studies to understand how the whole biological systems function. By studying the relationships and interactions between various parts of the biological system (NB in our case), including DNA copy number, methylation patterns, mRNA, miRNA, and protein levels, cell growth, clinical parameters (age, stage and outcome (survival)), it is hoped that eventually this will enable a more complete understanding of NB which will lead to improved survival of patients with minimal long term morbidity. The genome and proteome of a cell is a complex interrelated dynamic system. DNA copy number can impact the mRNA and miRNA expression. mRNA is transcribed into proteins and can contain miRNA sequences, and proteins control transcription by its action on DNA, mRNA and miRNA. In addition, miRNAs control protein and mRNA levels. These global interactions thus control the phenotype of a cancer cell which determines the outcome.

越来越清楚的是，单个基因在细胞内并不是孤立地起作用，而是与通路内的其他基因协同作用。此外，通路中的许多基因是冗余的，因此许多基因可以执行特定的功能，相反，单个基因可以根据其细胞环境具有许多功能。高通量全基因组方法允许研究细胞作为一个整体的复杂性。基因组学和蛋白质组学与功能分析的结合将被称为系统生物学。我的实验室利用这些系统的方法来更清楚地了解高危神经母细胞瘤的生物学。系统生物学旨在整合高通量生物学研究，以了解整个生物系统的功能。通过研究生物系统（在我们的病例中是NB）各部分之间的关系和相互作用，包括DNA拷贝数、甲基化模式、mRNA、miRNA和蛋白质水平、细胞生长、临床参数（年龄、分期和预后（生存）），希望最终能够更全面地了解NB，从而提高患者的生存率，并将长期发病率降低到最低。细胞的基因组和蛋白质组是一个复杂的相互关联的动态系统。DNA拷贝数可以影响mRNA和miRNA的表达。mRNA被转录成蛋白质，可以包含miRNA序列，蛋白质通过作用于DNA、mRNA和miRNA来控制转录。此外，miRNAs还控制着蛋白质和mRNA的水平。因此，这些全局相互作用控制了癌细胞的表型，从而决定了结果。