Research Methods
Applying cutting-edge genomic technologies to the study of lung disease
In the “post-genome world,” we have made astounding advances in our understanding of the molecular processes that govern how our cells function. But navigating the path from decoding our DNA to understanding disease is challenging because human cells are very complex. That’s why the genomic analysis of disease requires the use of sophisticated methods and technologies, including genome sequencing, genome-wide association studies, gene expression analysis, epigenetic analysis, and the science of bioinformatics.
The LGRC team is applying these tools in an innovative, complementary way to obtain a more complete picture of lung disease than could be had using any one method alone.
Genome Sequencing
What is it? Our genomes are comprised of more than three billion molecular building blocks called nucleic acids (or bases, referred to by the letters A, T, G, and C). The order of these bases constitutes the “code” that cells follow to manufacture the proteins our cells need for carrying out the functions vital for life. Genome sequencing determines the entire order of DNA bases in an individual’s genome.
Why do we use it? By examining and comparing DNA sequences among individuals, we can spot small differences in the series of bases—some as rare as a one base difference in the entire genome. This information can help us learn why some people are more likely than others to get lung disease, as well as determine how the disease comes about. This knowledge can help us develop better diagnostic screening tests and treatments.
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Genome-wide Association Studies (GWAS)
What are they? GWAS are a way to examine the patterns of genetic differences that are present among individuals, with the goal of identifying the common changes, or gene variants, found in people who have developed a particular disease.
Why do we use them? GWAS have already been used successfully to find gene variants that contribute to the development of cancer, heart disease, and diabetes. We are now applying this approach to lung disease research. The patterns of genetic differences we identify can serve as powerful diagnostic tools.
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Gene Expression Analysis
What is it? Although the DNA found in each cell of our bodies is identical, not all cells themselves are the same. Lung cells do a very different job from liver cells, kidney cells, brain cells, or other cell types. Cell types are set apart by which of their genes are “turned on” or “turned off” (or how they are expressed). In the same way, when a disease develops, cells change which genes they activate.
Why do we use it? Gene expression tells us a lot about how cells are functioning by revealing which, when, and how strongly genes are turned on in disease. The LGRC uses DNA microarrays, also called gene chips, and DNA sequencing methods to measure the expression of all 25,000 genes in our genomes. For example, by comparing patterns of gene expression found among different groups of patients, we hope to learn why some patients respond to treatment while others do not.
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Epigenetic Analysis
What is it? One of the ways that cells can control which genes are turned on or off is by chemically modifying their DNA without changing the DNA’s base sequence. The most common alteration is called methylation. The study of methylation is called epigenetics.
Why do we use it? Epigenetic analysis gives us information that complements DNA sequencing data, GWAS analysis, and expression analysis. Taken together, these methods help us uncover how changes in the DNA and gene expression interact in the disease process.
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Bioinformatics
What is it? All the technologies that we employ produce huge amounts of information—millions and millions of pieces of data on every patient. Bioinformatics is a young science that lies at the intersection between biology and computer science. It involves sorting through and making sense of data—in other words, uncovering what the data are telling us about a disease.
Why do we use it? The LGRC is using bioinformatics software and analytical methods to collect, manage, analyze, and interpret massive quantities of data. We map data back to the human genome, to the genes within the genome, and to the pathways and networks that cells use to carry out such functions as living, growing, multiplying, and adapting to their environment. Bioinformatics methods also help us organize information, so that we can share it with the lung disease research community. With more eyes looking closely at this data, we hope to accelerate the process of understanding, diagnosing, and treating lung disease.
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