Proteomics Center Devises Method for Assigning Probabilities to Human Protein InteractionsJanuary 25, 2008The Stowers Institute's Proteomics Center has published a novel method of using normalized spectral counts derived from a series of affinity purifications analyzed by mass spectrometry (APMS) to generate a probabilistic measure of the preference of proteins to associate with one another. The work - which allows for the assignment of probabilities not only to the interactions within well-defined protein assemblies, but also to interactions between complexes - was posted today to the Web site of the Proceedings of the National Academy of Sciences (PNAS). Large-scale APMS studies have played important roles in the assembly and analysis of comprehensive protein interaction networks for lower eukaryotes, such as yeast. But the development of such networks for human proteins has been slowed by the high cost and significant technical challenges associated with systematic studies of protein interaction.
The Stowers Institute's Proteomics Center has addressed this challenge by developing a method for building local and focused protein networks. With this computational approach, the probability for two proteins to associate is calculated from the bait-to-prey relationship alone, an improvement over other methods requiring systematic reciprocal bait-prey interactions or co-purification of preys by a third bait. "Previous protein interaction networks built using protein mass spectrometry data were largely based on binary 'yes/no' data, where a protein is present in a sample or it is not," explains Michael Washburn, Ph.D., Director of Proteomics and senior author on the paper. "We were interested in quantitative proteomics approaches. We were able to develop a method to generate more information-rich networks, where the preference of two proteins to associate within a defined complex or within a larger network assembly can be estimated using Baysian probabilities. The new approach adds more information to the analysis of protein complexes and networks, since not all proteins interact in the same way." The work not only provides a significant advancement in proteomic analysis, it also holds promise in facilitating the development of treatments for disease. "By having insight regarding the most probable contacts within a multiprotein complex, we can devise targeted strategies to disrupt specific interactions," said Mihaela Sardiu, Ph.D., Postdoctoral Research Associate and lead author on the paper. "This could be useful for developing new drugs for disrupting protein complexes involved in disease." The Proteomics Center is one of three technology development centers that support research at the Stowers Institute. In addition to collaborating with Stowers Institute independent research teams, the centers pursue cutting-edge solutions to the evolving s challenges of basic biomedical research. "The Stowers Institute's Proteomics Center is providing technology solutions that fundamentally change the way that Stowers researchers approach their work," said Robb Krumlauf, Ph.D., Scientific Director. "Because of the support provided by our technology development centers, Stowers research teams can approach long-standing problems in new and innovative ways, elevating their research and results." Additional contributing authors from the Stowers Institute include Yong Cai, Ph.D., Research Specialist I; Jingji Jin, Ph.D., Senior Research Associate; Selene Swanson, Research Specialist II; Ronald Conaway, Ph.D., Investigator; Joan Conaway, Ph.D., Investigator; and Laurence Florens, Ph.D., Managing Director of Proteomics. More information about the Stowers Institute's Proteomics Center is available at www.stowers-institute.org/labs/WashburnLab.asp. About the Stowers Institute Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality. Stowers Institute | |||||||||||||||||||||
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Related Proteomics Current Events and Proteomics News Articles Genetic Engineering & Biotechnology News reports on growing role of molecular diagnostics Novel platform technologies and key advances in genomics are rapidly driving the development of molecular diagnostics, reports Genetic Engineering and Biotechnology News (GEN). Saliva proteins could help detection of oral cancer Clinicians could detect oral squamous cell carcinoma, a form of oral cancer, using a simple test that detects proteins in saliva, according to a report in the October 1, 2008, issue of Clinical Cancer Research, a journal of the American Association for Cancer Research. Conaway Lab Identifies Novel Mechanism for Regulation of Gene Expression The Stowers Institute's Conaway Lab has demonstrated that an enzyme called Uch37 is kept in check when it is part of a human chromatin remodeling complex, INO80. The results were published in today's issue of Molecular Cell. Purifying parasites with light Researchers have developed a clever method to purify parasitic organisms from their host cells, which will allow for more detailed proteomic studies and a deeper insight into the biology of organisms that cause millions of cases of disease each year. How plants fine tune their natural chemical defenses Even closely related plants produce their own natural chemical cocktails, each set uniquely adapted to the individual plant's specific habitat. Innate immune system targets asthma-linked fungus for destruction A new study shows that the innate immune system of humans is capable of killing a fungus linked to airway inflammation, chronic rhinosinusitis and bronchial asthma. Newly discovered proteins in seminal fluid may affect odds of producing offspring Seminal fluid contains protein factors that, when transferred from a male to a female at mating, affect reproductive success. This is true of many different animals, from crickets to primates. Bacteria reveal secret of adaptation at Evolution Canyon Bacteria living on opposite sides of a canyon have evolved to cope with different temperatures by altering the make-up of their 'skin', or cell membranes. Scientists have found that bacteria change these complex and important structures to adapt to different temperatures by looking at the appearance of the bacteria as well as their genes. Protein marker for schizophrenia risk A protein found in immune cells may be a reliable marker for schizophrenia risk, report researchers in a new proteomics study appearing in the July issue of Molecular and Cellular proteomics. Hepatitis C virus may need enzyme's help to cause liver disease A key enzyme may explain how hepatitis C infection causes fatty liver - a buildup of excess fat in the liver, which can lead to life-threatening diseases such as cirrhosis and liver cancer, report University of Pittsburgh Graduate School of Public Health and School of Medicine researchers. More Proteomics Current Events and Proteomics News Articles |
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