BIOINFORMATICS: SYSTEMS BIOLOGY OF NEUROBLASTOMA

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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.