Software to improve efficiency of medical research

November 2, 2006

A data-finding tool that promises to dramatically improve the efficiency of medical research has been developed by a small team of ASU researchers.

The computer software program called Collaborative Bio Curation, or CBioC, can analyze vast amounts of biomedical data to locate and extract specific information critical to research efforts. It's a fusion of computer science, information management, medical research methods and clinical practice that could lead to significant advances in the way scientific data searches are conducted, says CBioC developers Chitta Baral and Graciela Gonzalez. Download Full Image

The quantity of biomedical literature worldwide increases on average by more than 1,000 articles and research papers each day, making it almost impossible for researchers to keep up with the latest findings, says Baral, a professor in ASU's Department of Computer Science and Engineering, and an affiliate faculty member with the Department of Biomedical Informatics. Both departments are part of the university's new School of Computing and Informatics.

CBioC is expected to save researchers the time and effort of wading through hundreds of thousands of articles to locate specific information relevant to their particular research, Baral says.

CBioC can be compared to Wikipedia in its collaborative capabilities, and to Google in its search capabilities, although Google searches only by terms and not by higher-level concepts.

For example, a Google search can find occurrences of information in medical literature about a specific gene. But Google doesn't produce the results provided by CBioC when performing a search for concepts such as “genes related to brain cancer,” or data on gene-disease relationships or protein interactions that are crucial to understanding diseases and the development of new therapies.

The program is a Web browser application that is a search engine and collaboration tool of PubMed, the primary online repository of biomedical papers maintained by the National Library of Medicine.

CBioC runs in a small frame at the bottom of the browser each time a researcher uses PubMed. When an article is selected, CBioC extracts and displays the facts reported in the article. For example, extracted facts that a certain gene has been found to be linked to brain cancer are added to the CBioC database. Similar facts then can be searched from within CBioC.

CBioC allows individual researchers to vote on the correctness of the extracted facts and enables them to share notes and comments about the data among colleagues and other PubMed users. Over time, a consensus is reached among researchers as to which facts are correct, enabling information to be updated and kept accurate, Baral says.

Use of CBioC has been steadily increasing since it became available in December. Researchers throughout the United States , Japan , Australia and Europe are downloading the software. It also caught the attention of Science magazine, which featured CBioC in the NetWatch news section of its Web site.

Gonzalez, an ASU biomedical informatics researcher, says she and Baral are exploring ways to make CBioC useful to a wider range of biological and medical research endeavors.

“We've been talking with the Biodesign Institute at ASU about adapting the software to look for sugar and gene relationships,” Gonzalez says. “We're also working with TGen (the Translational Genomic Research Institute in Phoenix ), exploring its applications for cancer research.”

Collaborative Bio Curation is available for free download at the Web site (">">


Move over, penicillin: Researchers mold clay into potential therapy

November 2, 2006

Clay is most commonly associated with the sublime experience of the European spa, where visitors have been masked, soaked and basted with this touted curative since the Romans ruled. If ASU geochemist Lynda Williams and microbiologist Shelley Haydel’s research on the antibacterial properties of clays realizes its full potential, smectite clay could one day rise above cosmetic use to take its place among antibacterial behemoths like penicillin.

“We use maggots and leeches in hospitals, so why not clay?” Haydel asks. “I had a professor in graduate school say, ‘Maybe, perhaps once in your life, in your scientific career, you’ll come across something that can change the world.’ Sometimes, I think: ‘Is this it? Will this help some people?’ ” Download Full Image" alt="" width="300" height="206" />

Microbiologist Shelley Haydel and geochemist Lynda Williams are taking a closer look at the antibacterial properties of clays for use as a future therapy.

Theirs is an unusual research pairing. They each are in the College of Liberal Arts and Sciences, yet both are pursuing different lines of scientific discovery. Williams is an associate research professor in the School of Earth and Space Exploration and studies clay mineralogy. Haydel is an assistant professor and expert in tuberculosis in the School of Life Sciences and with the Center for Infectious Disease and Vaccinology in the Biodesign Institute at ASU.

“People are interested in natural cures, and I think that there is a lot of nature that we don’t understand yet,” Williams says. “What if we discover a mechanism for controlling microbes that had never been discovered before? It is these avenues, at the boundaries of scientific discovery, at the edges of my field and knowledge (and Shelley’s), where such discoveries are made.”

National Institutes of Health (NIH) program directors agree. They have awarded a $438,970 grant over two years to Williams and Haydel for the study of clay mineral alternative treatment for Buruli ulcer, a flesh-eating bacterial disease found primarily in central and western Africa. What makes this award even more interesting is the rarity for a geochemist to net a NIH grant.

Alternative studies

The National Center for Complementary and Alternative Medicine at NIH was established in 1998 for just this kind of study. As one of the 27 institutes making up NIH, the center funds scientific research and technologies that examine herbal remedies, such as dandelion, green tea, valerian and horse chestnut, and practices such as acupuncture, tai chi and reiki that fall outside conventional medicines.

The ASU duo will examine the mechanisms that allow two clays mined in France to heal Buruli ulcer, which has been declared “an emerging public health threat” by the World Health Organization (WHO). Related to leprosy and tuberculosis, the Mycobacterium ulcerans produces a toxin and lesions, and it destroys the fatty tissues under the skin.

“The toxin is immunosuppressant; the patients feel no pain, and the body mounts no response to infection,” Haydel says. “It leads to disfigurement, isolation, not unlike that seen in leprosy. Traditional antibiotics can only make a difference at the very earliest stages of the disease, so treatments have largely been confined to amputations or surgical excision of the infected sites.”

This means that, if the clays are antibacterial in nature and the locus for that activity can be isolated, they may represent a new form of treatment.

“And they could be produced and distributed cheaply,” Williams says.

Humanitarians answer challenge

So how did a clay mineralogist whose background is in low-temperature geochemistry become involved with a health care project centered in the Ivory Coast? It’s the scientific equivalent of an online dating service: “I answered a posting on the Clay Mineral Society’s listserv placed by Thierry Brunet de Courssou,” Williams says. “He was asking to have someone take high-resolution scanning electron micrographs of the clays. I confess that we all ignored him, initially.”

According to the Brunet de Courssou Web site, the family has been operating health clinics on the Ivory Coast and in New Guinea. For a decade, Line Brunet de Courssou, Thierry’s mother, had been importing two French clays to treat people with Buruli ulcer and was getting startling results, while her use of native clays had no effect. Williams reviewed the mother’s work and notes that “Line Brunet de Courssou was a careful observer.” However, Line Brunet de Courssou was not a scientist. The mother, who is deceased, approached the WHO in 2002 at its fifth advisory group meeting on Buruli ulcer, having documented more than 50 cases of healing with the clay treatments. WHO documents indicate that the organization was receptive, calling her results “impressive.” But she notes that funding was denied for lack of scientific study.

Williams, from a family of physicians, says that it was really the second message that finally drew her to the project.

“He said, ‘I guess that no American scientists are interested in helping poor people in Africa,’ ” she says.

He guessed wrong. Armed with 100 grams of green powder (clay high in reduced iron), Williams took the micrographs of the minerals, then went a step further and examined their crystal structure and chemical compositions. She recruited Haydel to the project before the microbiologist arrived at ASU in 2005. Haydel brought more than 13 years of experience with pathogenic bacteria to the project. Within two months of Haydel’s arrival, they submitted the grant proposal to the NIH.

“I approached this work from the viewpoint of a clinical microbiologist,” Haydel says. “I ordered bacterial strains that pharmaceutical companies use to test their antimicrobials.”

Haydel and Williams tested both of the French clays that Brunet de Courssou had been importing. One inhibited pathogenic Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa (often a problem as an opportunistic infection in burn wards) and Mycobacterium marinum (related to Mycobacterium ulcerans, which causes Buruli ulcer disease). The clay was also found to partially inhibit the growth of pathogenic Staphylococcus aureus, including a multi-drug resistant variety.

“The other clay actually helps the bacteria to grow,” Haydel says.

So what makes one clay kill bacteria, and the other promote growth? And why do most clays tested have no effect? Williams’ and Haydel’s research can help answer such questions.

Clay’s properties fuel interest

Williams’ career fascination with clay started when she was a mineral exploration geologist looking for ore deposits. She worked with the “father of clay mineralogy,” Bob Reynolds, at Dartmouth College. Later, as a research associate at Louisiana State University, a colleague was studying geophasia – eating clay, a behavior seen in animals and people.

“In the South Appalachian Mountains, poor women would eat the local clay to help soothe nausea and stomach ailments, particularly during pregnancy. The clay was rich in kaolinite. (Kaolinite is the major ingredient in the over-the-counter remedy Kaopectate). But one day, they ran out of clay and moved over to another mountain and people began dying. We wanted to know why.”

The key to clay’s variable nature seems to be its structure.

“Clay is a mineral; it has a crystalline structure that is both flexible and fluid,” Williams says.

She likens them to very thin, 2-nanometer-thick slices of bread in a “peanut butter-and-jelly sandwich.” The “bread” is composed of three regions: two silicate layers with tetrahedral rings bounding an octahedral core. The “peanut butter” is the charged cations – for example, potassium – that stick to the negatively charged tetrahedral ring surface. The “jelly” can be organic compounds or other species of any or no charge. This interlayer, as the peanut butter and jelly are termed, can vary in width and composition, depending on the kinds of waters and elements present when it was formed. It is this interlayer where much of the elemental variability between clays can be found. And the interlayer surface area is huge (greater than 100 square meters per gram of clay – bigger than a football field). As a result, surface chemical reactions from these sites have an enormous impact on the geochemistry of the local environment.

Crystal structure, the interlayer, the way other materials, metals, ions bind to clays, the absorptive characteristics of clays, all could potentially play a role in the antibacterial activity they find in the one French clay. And, while preliminary results suggest that the antibacterial activity is associated with the interlayer, crystal size and structure also seem to play a role. It is a mystery that engages both research partners.

“It’s fascinating,” Haydel says. “Here we are bridging geology, microbiology, cell biology – transdisciplinary sciences, exactly what (ASU President) Michael Crow has been promoting. A year ago, I’d look at the clay and say, ‘Well, that’s dirt.’ Now I know a little something about clay structure; Lynda knows a little bit about microbiology. Alone, we each would have had to study for years; together, we are partnering these disciplines with synergy that really works.”

Margaret Coulombe

Director, Executive Communications, Office of the University Provost