AL | Science News
Novel Algorithm Helps Accelerate Drug Discovery
Scientists have designed a computer algorithm that allows them to investigate the action of drugs inside the body. Te new algorithm, called DeMAND (Detecting Mechanism of Action by Network Dysregulation), entails creating a computational model of the network of protein interactions that occur in a diseased cell. Next, the researchers perform experiments to track gene expression changes in diseased cells as they are exposed to a drug of interest. Te algorithm combines data from the model with data from the experiments to identify the complement of proteins most affected by the drug.
DeMAND improves on more labor-intensive and less efficient methods that can only identify targets to which a compound binds most strongly. Te new algorithm identifies many molecules that are affected in addition to the drug’s direct target, which provides a more comprehensive picture.
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A new database populated with validated test results enables scientists to access and compare real-world data and select the most reliable antibody for each experiment. Using the database, researchers can access detailed information about the accuracy and specificity of more than 100 commonly used and commercially available histone antibodies.
Te testing method used to populate the database is based on custom-designed peptide micro- arrays developed by Brian D. Strahl, Ph.D., co-senior study author and professor of biochemistry and biophysics in the University of North Carolina School of Medicine and his colleagues. Te arrays present a library of all of the chemical modifications or “tags” known to occur on histone proteins. Analyzing antibodies that are developed to target these different tags on the arrays quickly illuminates the types of tags to which each antibody is capable of binding.
Te web portal focuses on histone antibodies, a subset of antibodies that are central to the fast- growing field of epigenetics. Epigenetics researchers examine how layers of information outside the genome control the “on” and “off” state of genes, much like a light switch, that in turn affect all aspects of human health. Scientists use histone antibodies to track the roles of various proteins in this vital process of gene regulation.
Carriers of Mutant Gene More Susceptible to Liver Disease
Researchers at Kumamoto University and the Japanese Red Cross Kumamoto Hospital have discovered a gene mutation that contributes to nonalcoholic fatty liver disease (NAFLD)—which is associated with obesity—in subjects of normal weight. The researchers concluded that carriers of this mutant genotype (PNPLA3) were at greater risk for NAFLD and other health problems than noncarriers, even in normal-weight carriers.
Both a cross-sectional study of 740 subjects and a retrospective longi-tudinal study of 393 sub- jects who had five years of available medical records were conducted. Subjects with habitual alcohol intake and/or with positive hepatitis B and C tests were excluded from analysis regarding the risk for NAFLD. The associations between the genotype and the risk of NAFLD or a decline in renal function were analyzed among overweight (BMI >25 kg/m2 <25 kg/m2
) and normal-weight (BMI ) subjects.
Preliminary findings from Dr. Kentaro Oniki’s group showed that even normal-weight carriers of the mutant genotype (about 20% of all Japanese people) are at higher risk for NAFLD and renal function dysfunction than those without the gene. Tis suggests that the mutation may be used for early classification of individuals at high risk for NAFLD and decreased renal function, no matter their weight.
AMERICAN LABORATORY • 5 • AUGUST 2015 Laboratory Process Electrochemistry
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