Category Archives: Transhuman News

IMAGE:Using the zebrafish facility at Washington University School of Medicine in St. Louis, graduate student Sarah Ackerman (left) and senior author Kelly Monk, PhD, identified a gene that regulates how... view more

Credit: Robert Boston

Scientists have identified a gene that helps regulate how well nerves of the central nervous system are insulated, researchers at Washington University School of Medicine in St. Louis report.

Healthy insulation is vital for the speedy propagation of nerve cell signals. The finding, in zebrafish and mice, may have implications for human diseases like multiple sclerosis, in which this insulation is lost.

The study appears Jan. 21 in Nature Communications.

Nerve cells send electrical signals along lengthy projections called axons. These signals travel much faster when the axon is wrapped in myelin, an insulating layer of fats and proteins. In the central nervous system, the cells responsible for insulating axons are called oligodendrocytes.

The research focused on a gene called Gpr56, which manufactures a protein of the same name. Previous work indicated that this gene likely was involved in central nervous system development, but its specific roles were unclear.

In the new study, the researchers found that when the protein Gpr56 is disabled, there are too few oligodendrocytes to provide insulation for all of the axons. Still, the axons looked normal. And in the relatively few axons that were insulated, the myelin also looked normal. But the researchers observed many axons that were simply bare, not wrapped in any myelin at all.

Without Gpr56, the cells responsible for applying the insulation failed to reproduce themselves sufficiently, according to the study's senior author, Kelly R. Monk, PhD, assistant professor of developmental biology. These cells actually matured too early instead of continuing to replicate as they should have. Consequently, in adulthood, there were not enough mature cells, leaving many axons without insulation.

Monk and her team study zebrafish because they are excellent models of the vertebrate nervous system. Their embryos are transparent and mature outside the body, making them useful for observing developmental processes.

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Scientists find gene vital to central nervous system development

Researchers from Dartmouth's Norris Cotton Cancer Center, led by Casey S. Greene, PhD, reported in Pacific Symposium on Biocomputing on the use of denoising autoencoders (DAs) to effectively extract key biological principles from gene expression data and summarize them into constructed features with convenient properties.

"Cancers are very complex," explained Greene. "Our goal is to measure which genes are being expressed, and to what extent they're being expressed, and then automatically summarize what the cancer is doing and how we might control it."

Normally, it is difficult to apply computational models across different studies because the gene expression data is "noisy," meaning that there are many factors that differ in the way gene expression is measured. To begin their analysis, Greene's team added more noise to the data and then trained a computer to remove the noise. To remove the noise, the computer had to learn about key underlying features of breast cancer. "This approach of removing noise makes the models we constructed more generally applicable," Greene said.

Greene and the Dartmouth team studied DAs, which train computers directly on the data without requiring researchers to provide known biological principles to the computer, as a method to identify and extract complex patterns from genomic data. The model that the computer constructs can then be compared to previous discoveries to understand where data supports those discoveries and where the data raises new questions. The performance of DAs was evaluated by applying them to a large collection of breast cancer gene expression data. Results show that DAs were able to recognize changes in gene expression that corresponded to the cancers' molecular and clinical information.

"These techniques and findings will enable others to use the DAs to evaluate gene expression data in a variety of disease sites," reported Greene. "While noise in data is usually viewed as a problem, adding noise to data can actually be a good thing because it can help reveal the underlying signal. When we did this to analyze data from breast cancers, we found gene expression features that generalize across studies and represent important clinical factors."

Next for Greene's research team are more complex models that take multiple levels of regulation into account. Their goal is to develop methods that not only model data but that can automatically explain to researchers what the models have learned.

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Dr. Greene and his team of investigators do their research at Dartmouth's Norris Cotton Cancer Center in Hanover and Lebanon, New Hampshire. Their work is supported in part by NIH funding P20 GM103534 and the American Cancer Society Grant #IRG-82-003-27.

About Norris Cotton Cancer Center at Dartmouth-Hitchcock

Norris Cotton Cancer Center combines advanced cancer research at Dartmouth and the Geisel School of Medicine with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center, at Dartmouth-Hitchcock regional locations in Manchester, Nashua, and Keene, NH, and St. Johnsbury, VT, and at 12 partner hospitals throughout New Hampshire and Vermont. It is one of 41 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu

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Noisy data facilitates Dartmouth investigation of breast cancer gene expression