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Fighting Lymphoma Cancer with Genomics and Supercomputing

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Posted January 28, 2016

Lymphoma is cancer that begins in infection-fighting cells of the immune system. These cells are in the lymph nodes, spleen, thymus, bone marrow, and other parts of the body. When you have lymphoma, the cells change and grow out of control.

Researchers at The University of Texas at Austin (UT Austin) are studying lymphoma and, specifically, the transcription factor, FOXP1. A transcription factor is a DNA-binding protein involved in the process of converting, or transcribing, DNA into RNA. It has been known that FOXP1 is over expressed in one of the most aggressive B-cell non-Hodgkin lymphomas. This type of lymphoma is very aggressive with a low survival rate and a high rate of relapse after chemotherapy treatment.

Joe Dekker and Daechan Park from UT Austin published a paper in Proceedings of the National Academy of Sciences (PNAS)” on FOXP1.

Image credit: TACC

Image credit: TACC

“What was known before our study was that FOXP1 was highly over expressed; we didn’t know if it had any actual genetic or functional role in these tumors,” Dekker said.

After conducting various wet lab experiments such as cell viability assays, microarrays, and next-generation sequencing, the duo decided to incorporate sequencing data from the Genotypes and Phenotypes database maintained by the National Institutes of Health, which contained real patient data — they ended up with 10 terabytes.

Through a UT Austin allocation, Park, who has been using supercomputers in his research since 2009, used the Lonestar and Stampede supercomputers to analyze both their and the database’s next-generation sequencing.

“When we get genome sequencing data we need to map the data onto the human genome. That process is very memory and CPU intensive,” Park said.

Left: Joe Dekker, PhD, Molecular Biosciences, College of Natural Sciences; Right: Daechan Park, PhD, Department of Chemical Engineering, Cockrell School of Engineering. Credit: TACC

Left: Joe Dekker, PhD, Molecular Biosciences, College of Natural Sciences; Right: Daechan Park, PhD, Department of Chemical Engineering, Cockrell School of Engineering. Credit: TACC

In just three days using the supercomputers, Dekker and Park were able to map all of the files. On their local laptop, this task would have taken months.

Said Dekker: “We were able to translate all of the data and ideas that we generated from our cell culture work in the wet lab to being able to take real human samples and match what we had discovered.”

Their findings:

  • FOXP1 is necessary for survival of this lymphoma in cell culture. When it is knocked out these cancer cells die.
  • FOXP1 helps prevent programmed cell death and is involved in enforcement of major pathways known to be very active in these cancers. Loss of FOXP1 in these cancer cells results in suppression of these highly active pathways.
  • The target genes directly controlled by FOXP1 have expression levels in human samples that correlate with this very aggressive B-cell non-Hodgkin lymphoma.

“In genomics, supercomputing power is very important to map data onto genomes, for gene assembly to sequence the whole genome, and stitching DNA fragments to build the full sequence,” Park concluded.

Source: TACC

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