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Finding useful links.
A new tool developed by a team led by Charles DeLisi, BU's Arthur G. B. Metcalf Professor of Science and Engineering and director of ENG's Bioinformatics Program, promises to help scientists make useful connections among the vast amount of data about proteins and genomic sequences generated over the past three decades, and better understand how they control life functions.

Now available online, Predictome is a relational database that can be used to predict links between the proteins of the genomes of 44 species. It uses both computational and experimental methods to generate links. Authors Joseph Mellor (ENG'04) and Itai Yanai (ENG'02), graduate students in the Bioinformatics Program, term the tool a "hypothesis machine" because it allows researchers to screen large sets of data and detect interesting relationships among proteins for further study.

While genes provide the building plan for a particular organism, it is the proteins produced by the genes that create and maintain the organism. In humans, for example, proteins not only are the chemical building blocks of tissue, but as hormones, enzymes, and antibodies, proteins also regulate how the body functions. By better understanding the complex interactions between proteins, scientists are gaining a better understanding of how cells function and what happens when they malfunction -- diseases such as cancer or diabetes, for instance.

Predictome combines computational information from published databases that link proteins closely associated in the genomic sequence, share the same evolutionary pattern, or are distinct in one organism but combined in another. It also includes protein links based on how they physically interact in experimental protocols. By integrating such a variety of approaches in a single database, Predictome yields a richer and more accurate source of possible protein links, which can be investigated further. The researchers expect to add more methods over time, including links based on data gathered from DNA chips and microarrays, as well as links based on automated literature searches for genes and proteins cited in the same publication. In addition, users of the database can submit links they have found.

Predictome is available online at http://predictome.bu.edu, and is described in the January 1, 2002, issue of Nucleic Acids Research.

Eating your Bs.
Researchers at the BU School of Medicine report that people with high levels of homocysteine in their blood are more than twice as likely to develop Alzheimer's disease (AD) and other dementias later in life. This relationship is particularly interesting since a reduction in the level of homocysteine in the blood has been associated with increased consumption of folic acid and vitamins B6 and B12.

Philip Wolf, a MED professor of neurology, and colleagues at MED and Tufts University derived their data from the Framingham Heart Study, the landmark heart study supported by the National Heart, Lung, and Blood Institute (NHLBI). The study has been collecting data on more than 5,000 residents of Framingham, Mass., since 1948.

Wolf and his team followed 1,092 people in a dementia-free group of the Framingham cohort who enrolled in the study between 1976 and 1978, at an average age of 76. Homocysteine levels were measured between 1979 and 1982, and again between 1986 and 1990. Between 1990 and December 2000, some 111 people from the group developed dementia, including 83 specifically diagnosed with AD. Those who had more than 14 micromoles per liter of the amino acid in their blood were twice as likely to have developed AD; the risk of developing AD increased by 40 percent for each five micromoles per liter above that level. Those with consistently high levels of homocysteine were at highest risk.

The study found the association to be independent of other risk factors, including age, gender, or the presence of the variant of the APOE gene that is associated with AD.

The scientists are continuing to study the relationship between dietary consumption of folic acid and vitamins B6 and B12 and the development of AD. They speculate that consuming adequate amounts of these vitamins may help reduce levels of homocysteine in some individuals. Another NHLBI-supported study -- the DASH (Dietary Approaches to Stop Hypertension) diet (see "Research Briefs," January 25, 2002) -- suggests that a diet rich in green leafy vegetables, low-fat dairy products, citrus fruits and juices, whole wheat bread, and dry beans can significantly lower blood levels of the amino acid. "Although there is no evidence that reducing homocysteine levels will prevent AD or cardiovascular disease, a healthy diet, low in fat and rich in nutrients, is always a good idea," says Wolf.

This study was supported by the National Institute on Aging and appeared in the February 14 issue of the New England Journal of Medicine.

"Research Briefs" is written by Joan Schwartz in the Office of the Provost. To read more about BU research, visit http://www.bu.edu/research.

22 February 2002
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