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How cells change gears: New insights published in Nature Genetics
Date:4/20/2009

ls. Understanding the role of the transcriptional network during differentiation in leukemia cells could offer a glimpse into the cause of leukemia, or offer possible approaches for treating leukemia, according to Ravasi.

During the laboratory phase of the project, researchers introduced a compound that stopped cell proliferation in the myeloid leukemia cell line. Next, they collected as much information as possible regarding the activity of the transcription factor network during the processes of differentiation and maturation into immune cells known as monocytes and macrophages. Computational work performed at UC San Diego after all the laboratory data had been collected allowed the researchers to identify specific subnetworks of transcription factors that were activated at particular time points.

Integrative Biology

The UCSD researchers were challenged to integrate different but related data sets in order to tease out real signals from noise. This is known as "integrative biology."

"We take lots of measurements of the same thingwe integrate them together," which leads to higher confidence in experimental results, Ravasi explained. Measuring both messenger RNA and protein levels, is one example. Detection of both signals provides two independent data points indicating the presence of the same protein.

"Getting to be the first to analyze and make sense of this large and fascinating data set was a huge opportunity," said Ravasi. The UC San Diego bioinformatics team working on this project included Ravasi and two post-doctoral researchers from Trey Ideker's bioengineering laboratory, Ariel Schwartz, now at Synthetic Genomics, and Kai Tan, now an assistant professor of internal medicine and biomedical engineering at the University of Iowa.

By monitoring the activity of the transcriptional network one hour after the onset of differentiation, the researchers identified a gene that appears to play an important
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Contact: Daniel Kane
dbkane@ucsd.edu
858-534-3262
University of California - San Diego
Source:Eurekalert  

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