| As genomic technology continues to advance, investigators are able to acquire unprecedented information about a diverse array of cellular properties, offering new opportunities to understand the fundamental complexity of cellular phenotypes. In turn, cancer biologists have begun to integrate genomic technologies into their experimental approaches, improving our understanding of oncogenic phenomena. With our increased capacity to characterize the components of cellular processes it has become clear that similarly sophisticated analytical, computational, and experimental techniques are needed to more completely exploit the power of genomic approaches. This will require refining basic analytical strategies that are extensible to diverse experimental contexts, effectively combining existing genomic techniques with well-defined systems, and developing novel experimental strategies to creatively address outstanding biological questions. Here, I present three experiments encompassing distinct aspects of the challenges and opportunities presented by genomic technology. First, I describe an experiment in which I developed a strategy for detecting single nucleotide variants in massively parallel RNA sequencing data, and applied this technique to characterize nucleotide diversity in a panel of primate species. Next, I discuss a study in which I performed a microarray experiment in a model of omental metastasis to identify the transcriptional components of MKK4-mediated metastasis suppression. Finally, I describe an experiment in which I used species information to separately estimate tumor and stromal gene expression in RNAseq data from xenograft tumors, and identified transcriptional and compositional changes to the microenvironment related to invasive and noninvasive phenotypes. In addition to their specific biological insights, these experiments collectively represent a holistic approach to genomics that includes developing formal genomic techniques and integrating them with rigorous experimental designs. |
