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Big Data Consortium to Advance Neuromuscular Disease Research

By LabMedica International staff writers
Posted on 05 Oct 2014
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A five-center consortium has been initiated in the United States to gather and analyze thousands of bits of data to develop a global outlook of neuromuscular disorders.

Investigators from the Cedars-Sinai (Los Angeles, CA, USA) Board of Governors Regenerative Medicine Institute reported that have received a grant from the US National Institutes of Health (NIH; Bethesda, MD, USA) to participate in a consortium taking the study of motor neuron disorders—such as Lou Gehrig’s disease and spinal muscular atrophy—to a new, comprehensive outlook.

“We will be working as part of an NIH initiative to create databases of disease ‘signatures’ by generating and analyzing thousands of data points. Scientists often focus on very small things, such as a single signaling pathway in cells or a single gene or protein that is involved in some way with disease development, but identifying and correcting one component rarely leads to a cure. This is especially true in the brain because its networks are very complex,” said Clive Svendsen, PhD, professor and director of the Board of Governors Regenerative Medicine Institute, and lead investigator of Cedars-Sinai’s part of the study.

Dr. Svendsen compares this change in perspective to the way meteorologists began predicting weather—viewing global trends and collecting huge amounts of data to create a forecast for a specific place and time. The grant is part of an NIH initiative called the Library of Integrated Network-based Cellular Signatures (LINCS) program, which has a goal to develop a “library’ of molecular signatures that describes how different cells respond to proteins, genes, chemicals—basically anything that may come in contact with or alter the cell or its activity.

Cedars-Sinai is a member of a group, NeuroLINCS, studying motor neuron disorders, which include Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. The NeuroLINCS study will be coordinated by researchers at the University of California, Irvine (USA), with additional collaborators at the Gladstone Institutes at the University of California, San Francisco (USA), Johns Hopkins University (Baltimore, MD, USA), and the Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard (Cambridge, MA, USA).

NeuroLINCS is one of six consortiums recently funded through NIH’s LINCS program to study diabetes, cancers and other diseases using cell lines and specialized stem cells called induced pluripotent stem cells.

The Board of Governors Regenerative Medicine Institute, which has developed a national reputation for the quality of its induced pluripotent stem cells, was asked to provide the stem cells for all of the consortiums. The cells are generated in the Regenerative Medicine Institute’s induced pluripotent stem cell core facility, directed by Dhruv Sareen, PhD, assistant professor of biomedical sciences and faculty research scientist with the department of biomedical sciences.

Cedars-Sinai and the Regenerative Medicine Institute also will play a major role in the data generation phase of the study. New technology enables scientists to “mine” data on a large scale, such as measuring millions of proteins in only one sample—an area of expertise for Jennifer Van Eyk, PhD, director of Cedars-Sinai’s Advanced Clinical Biosystems Research Institute. She will be co-lead investigator of Cedars-Sinai’s part of the study and will provide protein analysis for all NeuroLINCS collaborators. Other experts will collect data on genetic material and the way genetic information is relayed to proteins within cells.

Dr. Svendsen reported that the data analysis groups will collaborate to create computer programs to combine all the data together. “We may be looking at many thousands of data points, but using algorithms to create a ‘cloud’ of information, we expect to see a ‘signature’ emerge that shows us the relationships between proteins, genes and RNA in the cell. There will be a specific signature for healthy controls and a different one for the disease, such as Lou Gehrig’s,” Dr. Svendsen said. “Once we have that, we can try to ‘punch holes’ in the disease signature by hitting the cell with a small molecule to see how the cloud of information changes. The ultimate goal is to morph the disease cloud back into a healthy cloud. But right now, we don't know what the disease state is. This is what we want to find out.”

At Cedars-Sinai, Drs. Svendsen and Sareen frequently collaborate on ALS and other motor neuron disease studies with Robert H. Baloh, MD, PhD, director of neuromuscular medicine and the ALS Program in the department of neurology. “We have a strong mutual interest in developing personalized medicine for patients suffering from neurodegenerative diseases,” Dr. Svendsen said. “We want to be able to create in a dish the motor neurons that mirror an individual patient's disease so we can see how quickly or slowly degeneration occurs. We also want to be able to interact with the disease model and see if we can slow it down in the dish. If so, theoretically, we should be able to slow it down in the patient as well. Through the LINCS grant, big data technology enables us to explore motor neurons in greater detail and gives us a much more sophisticated way of producing and analyzing these personalized models.”

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