BIOINFORMATICS: SYSTEMS BIOLOGY OF NEUROBLASTOMA

越来越清楚的是，单个基因并不是在细胞内孤立地起作用，而是在通路中与其他基因协同起作用。此外，途径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，一个基因可以根据其细胞环境具有多种功能。高通量全基因组方法允许从整体上研究细胞的复杂性。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。系统生物学寻求整合高通量的生物学研究，以了解整个生物系统是如何运作的。通过研究生物系统(在我们的病例中为NB)不同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、分期和结果(生存))，希望最终这将使我们能够对NB有更全面的了解，从而以最低的长期发病率提高患者的生存率。细胞的基因组和蛋白质组是一个相互关联的复杂动态系统。DNA拷贝数可以影响mRNA和miRNA的表达。MRNA被转录成蛋白质，可以含有miRNA序列，蛋白质通过对DNA、mRNA和miRNA的作用来控制转录。此外，miRNAs还控制蛋白质和mRNA水平。因此，这些全球相互作用控制着癌细胞的表型，而表型决定了结果。

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.