Invitrogen Corp. and the Human Proteome Organisation (HUPO) have entered a scientific collaboration focused on advancing proteomic research through education initiatives, standardization of research protocols and development of advanced proteomic products. Under the terms of the collaboration, Invitrogen scientists will support efforts driven by HUPO and its members internationally to develop new proteomic standards, products and processes. Invitrogen will also support a number of global educational programs and resources. Financial terms of the collaboration were not disclosed.
“Our partnership with HUPO enables our researchers to work closely with thought leaders in the field of proteomics,” explained Gregory T Lucier, Chairman and Chief Executive Officer of Invitrogen Corp. “By improving education, training and technology development, our organization can provide scientists the ability to better understand critically important areas of research.”
By collaborating with leading protein laboratories internationally, Invitrogen and HUPO plan to foster a set of industry standards to enable large-scale data generation and analysis, consistent with HUPO’s mandate to shape the next phase of disease research and drug discovery. HUPO’s Education and Training Initiative offers programs to promote expertise in all areas of proteomics including sample preparation, protein separation, mass spectrometry, bioinformatics and experimental design.
“This is a great opportunity for HUPO and all its members to acquire and set standards that will become applicable worldwide,” said John JM Bergeron, President of HUPO. “This standardization effort, which is one of several that HUPO is spear-heading, is a major part of our organization’s mission, and will act as a major impetus to the implementation of worldwide proteomic standards.”
“The potential for improving the effectiveness of proteomics research is an extremely exciting part of our collaboration with HUPO,” concluded Norrie Russell, Chief Scientific Officer for Invitrogen. “By adding our strength in technology development to the many other groups supporting HUPO’s initiatives, we feel we can help proteomics realize its full potential in life sciences research.”
BioMachines announces new proteomics services division
BioMachines Inc., a biotechnology company that develops, manufactures and sells advanced automation tools to accelerate drug discovery and development, has announced a new services division, Applied Proteomics Services. The new division of BioMachines is the result of an agreement with the University of Massachusetts Medical School’s (MA, USA) Proteomic Fractionation Group (PFG). BioMachines will leverage the experience of University of Massachusetts Medical School researchers Sunny Tam and Douglas Hinerfeld to support the Applied Proteomics Services group.
The group provides diverse proteomic sample preparation, fractionation and mass spectrometry services for state-of-the-art analysis. Applied Proteomics Services will utilize its fully integrated technology platform to provide real advantages in data quality, throughput and the ability to review, interpret and troubleshoot experimental outcomes.
“This new relationship combines the deep knowledge and expertise of the PFG team with proven sample preparation automation equipment, to offer our customers the best combined set of resources on the market”, said Tom Larrichio, BioMachines’ Chief Executive Officer. “Protein-based biopharmaceuticals are enjoying great commercial success. Specifically, monoclonal antibodies are a very exciting area, where sales are projected to grow from a US$15 billion market in 2005 to a US$27 billion market in 2010. This is in addition to protein analysis that is required for small-molecule therapies. We are focused on this growing market by providing expertise in protein analysis through a fee-for-services model”, added Larrichio.
“We are delighted about this collaborative relationship with BioMachines, which will enable us to reach out and serve more clients in this exciting technology area. Our technology platform will be expanded and more biopharmaceutical applications utilizing our proteomic expertise will be created”, explained Sunny Tam, Research Associate and Professor of Biochemistry and Molecular Pharmacology.
Celera & Medarex collaborate in cancer research
Celera Genomics and Medarex, Inc. have announced the formation of a strategic collaboration to discover and develop fully human antibodies for the potential treatment of multiple cancer indications. The collaboration will encompass the development of therapeutic antibodies against proteins identified by Celera’s proteomic research discovery efforts as being overexpressed on the surface of tumor cells and subsequently validated through additional research at Celera. The collaboration combines Celera’s ability to discover and validate novel targets for oncology with Medarex’s expertise in the development of fully human antibody therapeutics.
Under the collaboration, Celera and Medarex plan to jointly select targets from Celera’s portfolio of novel cancer targets. Medarex expects to generate fully human monoclonal antibodies against these targets using its proprietary UltiMAb Human Antibody Development System®, and the two companies expect to jointly carry out initial validation studies. The two companies plan to alternate the selection of antigen–antibody research programs to further develop and commercialize the antibodies independently. The selecting party will have full development and commercialization rights to products arising from its selected research programs, and the other party will be entitled to receive milestone payments if milestones are achieved and royalties on commercial sales of any such products. The selecting company may develop antibodies generated under this collaboration internally or through external partners. Other financial terms of the agreement were not disclosed.
“We are pleased with this new collaboration with Medarex as it combines the strength of our novel target discovery and validation with their expertise as a leader in developing human antibody therapeutics”, said Kathy Ordoñez, President of Celera. “Our proteomics discovery platform continues to demonstrate value in identification of oncology targets for Celera and our partners, and this new relationship with Medarex allows us additional flexibility in advancing our broad pipeline of validated targets for additional future value.”
“We are pleased with this opportunity to work with Celera and to pair targets discovered by their proprietary technology with our UltiMAb technology. This collaboration provides us with an opportunity to further expand our base of potential new oncology therapeutics”, said Donald L Drakeman, President and Chief Executive Officer of Medarex.
Discovery of novel biomarkers linked to pre-eclampsia
Ciphergen Biosystems, Inc. announced the discovery of a panel of biomarkers present in urine that could distinguish pregnant women with pre-eclampsia from healthy pregnant women. The results were presented at the 15th World Congress of International Society for the Study of Hypertension in Pregnancy (ISSHP) in Lisbon, Portugal, July 2–5, 2006.
Irina A Buhinschi, Assistant Professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at Yale School of Medicine (CT, USA), presented a study in which 122 urine samples were analyzed for biomarkers to predict, diagnose and monitor the severity and treatment effectiveness of pre-eclampsia.
The researchers discovered the presence of two biomarkers (specific fragments of albumin and serpina-1) that, when combined, are highly characteristic for pre-eclampsia superimposed on chronic hypertension. The marker panel, assayed using Ciphergen’s surface-enhanced laser desorption/ionization (SELDI) time-of-flight (TOF) mass spectrometry (MS) technology, could classify the study subjects with 92% accuracy. “By identifying these protein biomarkers we gained further insight into the mechanisms related to the development of pre-eclampsia,” said Buhinschi. “The further development of a new test using these biomarkers could lead to earlier diagnosis and treatment of pre-eclampsia and help prevent premature births.”
Carl P Weiner, Professor and Chair, Obstetrics and Gynecology, University of Kansas School of Medicine, highlighted the role of genomics and proteomics, specifically SELDI-TOF-MS, in addressing the challenges of pre-eclampsia. During his presentation he indicated the primary goal of proteomics is biomarker discovery by sample stratification of normal versus disease, in which the study designs included samples from normal pregnant women, mild pre-eclampsia, severe pre-eclampsia, chronic hypertension and superimposed pre-eclampsia. He cited several promising studies that have revealed novel biomarkers for pre-eclampsia and may be indicators of disease susceptibility, onset and progression, as well as drug response or new therapeutic targets. “As you can see, pre-eclampsia is a complicated problem that requires a broad perspective of the pathologic events. Genomics and proteomics tools coupled with new software may facilitate that process and enhance the near-term likelihood of diagnostic and therapeutic success,” Weiner said in his concluding remarks.
“We are very excited to be working with Dr Buhinschi and Dr Weiner on addressing this important clinical condition which effects over 350,000 pregnancies and kills thousands of women annually in the United States. These findings represent advancements in our understanding of threatening disorders during pregnancy and could lead to better management of high-risk pregnancies,” said Gail S Page, President and Chief Executive Officer of Ciphergen Biosystems, Inc.
There are over 6.3 million pregnancies annually in the USA. Pre-eclampsia occurs in approximately 5–7% of all pregnancies and is responsible for 18% of maternal deaths during pregnancy, as well as a third of premature births.
Proteome Sciences license agreement in stroke
Proteome Sciences plc has announced a license agreement with one of the top ten global leaders in clinical diagnostics to use its biomarkers for the detection, diagnosis and monitoring of stroke. This is a new area for the licensee, who has determined not to disclose its identity at this time for competitive reasons. The biomarkers were discovered and validated using a combination of different proteomic approaches available for external use through the proprietary Proteo-SHOP® platform.
Stroke is the brain equivalent of a heart attack. Blood must flow in and through the brain for it to function. If its flow is obstructed by a blood clot moving to the brain or by narrowing or blocking of blood vessels, the brain loses its energy supply, causing damage to tissues and leading to stroke.
Annually, 15 million people worldwide suffer a stroke. Of these, 5.5 million die and another 5 million are left permanently disabled, placing a burden on family and community.
Stroke is the third leading cause of death in the USA (160,000 deaths), with annual costs of US$57.9 billion for stroke medical-related costs and disability, and is the single most common cause of severe disability. A total of 750,000 people are diagnosed in the USA annually having new or recent strokes.
Under the research license, a number of Proteome Sciences biomarkers will be tested in stroke for inclusion on a new panel for the licensee’s high-throughput diagnostic platforms.
Christopher Pearce, Chief Executive Officer of Proteome Sciences, said, “This licensee is world renowned in clinical diagnostics and has built a strong customer base ideally placed to introduce and support new stroke diagnostic products globally. This reflects their commitment to develop innovative assays and solutions to address the major unmet diagnostic and prognostic needs in stroke.
“They have been impressed by Proteome Sciences’ ProteoSHOP® technology to discover novel biomarkers in blood and to progress these rapidly for the market place. This agreement brings important new biomarkers to their in vitro diagnostic pipeline and the opportunity to diagnose stroke in a high-throughput system. We look forward to incorporation of our stroke markers onto their systems and to a rapid introduction of an high-throughput screening stroke test.”
Siemens to acquire Bayer Diagnostics arm
Siemens has signed an agreement with Bayer to acquire the chemical and pharmaceutical company’s Diagnostics Division. The acquisition will enable Siemens Medical Solutions to expand its position in the high-growth molecular diagnostics market. At the end of April, Siemens announced the planned acquisition of Diagnostic Products Corporation in the USA, a leading company in immuno diagnostics. The purchase price for Bayer Diagnostics, which had sales of US$1.4 billion and a double-digit EBITDA margin in 2005, is roughly US$4.2 billion.
“Demographic change is greatly increasing global demand for healthcare services and thereby generating excellent growth opportunities for Siemens,” explained Klaus Kleinfeld, Siemens President and Chief Executive Officer. “The acquisition of Bayer Diagnostics is part of our targeted strategy to create the healthcare industry’s first integrated diagnostics company by combining the entire imaging diagnostics, laboratory diagnostics and clinical information technology value chain under one roof.” Kleinfeld also noted that this acquisition, which is subject to regulatory approval, is further proof that Siemens is rigorously focusing its portfolio on promising growth fields.
Erich R Reinhardt, member of the Siemens Managing Board and President of Siemens’ Medical Solutions Group, commented, “Molecular medicine is becoming increasingly important since it enables healthcare professionals to identify the causes of disease using genetic profiles. With the help of molecular medicine, it will be possible not only to predict the effects of the medications selected and tailor treatment for individual patients, but also to diagnose disease at an early stage. The planned acquisition of Diagnostic Products Corporation has provided us with access to laboratory diagnostics. With the acquisition of Bayer Diagnostics, we will now have a comprehensive portfolio in this key future-oriented market. These deals will enable us to considerably expand our range of expertise and further our leading position as a trendsetter in healthcare.”
The two acquisitions will make Siemens Medical Solutions second worldwide in immunodiagnostics. In addition, the acquisition of the Bayer unit will enable the Siemens Group to tap the rapidly growing market for molecular diagnostics based on gene analysis (nucleic acid testing). Bayer Diagnostics is also a world-market leader in clinical chemistry with a leading position in near-patient testing, laboratory automation and hematology (blood cell diagnostics).
“We are convinced that the successful laboratory equipment business has even better prospects in a company specializing in medical technology. The decision to divest our Diagnostics Division is fully in line with our strategy for systematically aligning our healthcare business. We are concentrating on pharmaceuticals for both humans and animals, and products that can be promoted directly to patients,” commented Werner Wenning, Bayer AG Management Board Chairman.
Cognia introduce proprietary ubiquitin database
Cognia Corp., a pioneer in developing and aggregating biological information, has unveiled its first proprietary database, Cognia Catabolism, covering key regulatory proteins of the ubiquitin system.
The database, named Cognia Catabolism because of the ubiquitin system’s role in breaking down (catabolizing) cellular proteins, will contain expertly curated information found in the scientific literature to provide a comprehensive structured information resource on ubiquitin system molecules, their attributes and interactions.
“This will be an extremely important and widely used information source. Many pharmaceutical and biotech companies are developing drugs against targets in cellular pathways involved in oncology, CNS or inflammation where ubiquitin system proteins play an important role or are themselves potential drug targets,” said David M Rubin, Cognia Chief Scientific Officer and Senior Vice President of Product Management.
Rubin and colleagues at Cognia developed the database with guidance from an advisory board of world-renowned scientists, including Daniel Finley of Harvard Medical School (MA, USA) and Vincent Marchesi of Yale’s Boyer Center (CT, USA).
The ubiquitin protein is nearly identical in all creatures, from yeast to humans. Ubiquitin allows cells a highly efficient and specific means of regulating the levels of many key regulatory proteins through specific carefully controlled catalysis. The system plays a role in many normal as well as many aberrant cellular processes, and thus is of great interest to basic researchers and drug discovery scientists alike.
“Today, researchers have to search for this information one paper at a time; Cognia Catabolism brings an ordered searchable summary of the key ‘facts’ from the literature into the discovery workflow in real time,” Rubin added.
Cognia Catabolism (available from October on an annual subscription basis) integrates seamlessly into Cognia Molecular Information Center, a system for integrating public and third-party data along with scientists’ own experimental results. “Cognia Catabolism in Cognia Molecular enables scientists to instantaneously link their results with this powerful new database,” Rubin stated. Cognia Catabolism also can be delivered as a stand-alone database to integrate into current customer systems.
Asterand & Rubicon to collaborate on new cancer diagnostics
Asterand plc, the human tissue research services company, has announced a partnership with Rubicon Genomics to discover novel biomarkers for cancer diagnosis.
Under the nonexclusive agreement, Asterand will supply tissue and biofluid samples from its biorepository and its worldwide network of clinical collaborators. Rubicon will perform retrospective and prospective studies with the samples using its proprietary MethylPlex™ technology to discover more sensitive and specific methylated DNA markers for cancer diagnosis and prognosis.
DNA methylation is an important mechanism by which cells become cancerous and grow out of control. Several recent studies have demonstrated that specific methylated DNA sequences can be detected in the blood of various cancer patients. Thus, these modified DNAs can be sensitive markers for the presence of cancer.
“The current tests to detect cancer are often not sufficiently sensitive to detect cancer at an early stage”, said James Eliason, Chief Scientific Officer of Asterand. “This partnership will help Rubicon develop tests for detecting cancer sooner, in turn leading to more effective treatment.”
Over the last several years, Asterand has built a large bank of samples and biofluids together with associated data. This bank is now widely used by the world’s large pharmaceutical companies in their research programs. Under the agreement with Rubicon, Asterand will provide broad access to their biobank and research services in exchange for a royalty on diagnostic tests that are developed and marketed.
“This is an ideal area for our companies to collaborate,” commented Eliason. “Our extensive sample collection and expertise in sample characterization and annotation, combined with Rubicon’s technology for highly sensitive detection of methylated DNA sequences, will open up exciting discoveries in cancer detection and treatment.”
“Collaborating with Asterand will allow us to accelerate development of our diagnostic products,” added John Langmore, Vice President for Commercial Development at Rubicon. “Their samples and clinical data are critical to Rubicon’s success in developing superior tests that can fully exploit Rubicon’s breakthrough methods of detecting methylated DNA in routine samples of blood and urine. We look forward to developing more effective tests for detection and prognosis of colon, lung and breast cancer.”
Quest Diagnostics acquires Focus Diagnostics
Quest Diagnostics Inc., the leading provider of diagnostic testing, information and services in the USA, has completed the previously announced acquisition of Focus Diagnostics, Inc., in a cash transaction valued at approximately US$185 million.
Focus Diagnostics is recognized worldwide for its leadership in infectious and immunological diseases and has established a reputation for being first to introduce new assays to the market, including diagnostic tests for Lyme disease, West Nile virus and severe acute respiratory syndrome (SARS). In addition, Focus Diagnostics develops and markets diagnostic products, such as HerpeSelect® for herpes simplex virus.
Clinical laboratories to evaluate Tm bioscience test
Tm Bioscience, a leader in the commercial genetic testing market, has announced that to date more than 25 leading healthcare institutions and laboratories across North America, Europe and Asia have entered its Early Access Program to assess the ID-Tag™ Respiratory Viral Panel (RVP), a unique test that has the potential to play a key role both in the management of patients exhibiting respiratory distress in clinical settings and in countering the pandemic threat of respiratory viruses.
“Healthcare institutions around the world will benefit significantly from a test that can rapidly and reliably identify patients infected with respiratory viruses. Our panel will be evaluated in a variety of prestigious high-volume healthcare facilities that will provide us with important feedback, ensuring our test fully addresses their needs and is marketed effectively,” said Greg Hines, President and Chief Executive Officer of Tm Bioscience. “These institutions will also be able to gain experience with the ID-Tag RVP, allowing them to implement the test rapidly once it completes the regulatory approval process.”
Michael Mihalov, Chair of Pathology and Director of the Diagnostic Molecular Pathology Laboratory at Resurrection Medical Center (IL, USA), one of the institutions participating in the Early Access Program, said he expects the ID-Tag RVP to prove advantageous in testing for various respiratory viruses quickly, economically and accurately. “Our lab has had great success with Tm Bioscience products, and we are anxious to evaluate their respiratory panel. Current respiratory viral testing is time-consuming and inconvenient for a high-volume hospital serving thousands of patients in a large metropolitan area. ID-Tag RVP will help us identify respiratory viruses more rapidly and undertake appropriate intervention, whether that is treatment or isolation,” Mihalov said.
Tm Bioscience’s ID-Tag RVP is a proprietary, comprehensive test for the detection of 20 of the most common strains and subtypes of respiratory viruses, including respiratory syncytial virus A and B, influenza A (with subtyping) and influenza B. ID-Tag RVP is designed to play a key role in patient management, infection control and in countering the pandemic threat of respiratory diseases.
In January 2006, Tm Bioscience made the ID-Tag RVP commercially available as an Investigational Use Only device.
Epigenomics & Affymetrix announce agreement
Epigenomics AG, a molecular diagnostics company developing tests based on DNA methylation, and Affymetrix Inc. have announced that Affymetrix has granted Epigenomics nonexclusive access to Affymetrix microarray technology to develop and market microarray-based in vitro diagnostic tests for oncology and other indications.
The agreement complements Epigenomics’ previously announced strategic alliance with Qiagen NV for sample preparation. Together, with the Affymetrix arrays and DNA analysis instrumentation, Epigenomics can now provide a complete platform for its pathology tests based on its proprietary DNA methylation methods. The first products based on this platform will be pathology tests in prostate and breast cancer. As the first example, Epigenomics is planning to transfer its Molecular Classification Test (MCT) for prostate cancer onto the Affymetrix platform to use it in the pivotal clinical trial for US FDA approval of the assay, which is scheduled to start next year.
“The agreement is another important step to turn Epigenomics into an integrated diagnostics company,” said Alexander Olek, Chief Executive Officer of Epigenomics. “It has been our main focus over the last year to obtain gold standard solutions for our own diagnostic products so that we can start marketing must-have diagnostic products meeting the highest industry standards. The Powered by Affymetrix™ program allows us to join in to the Affymetrix open platform concept, which already provides Affymetrix diagnostic partners, among them several global players, with an excellent opportunity to benefit mutually from their respective strong placement power.”
“Last year, we closed a strategic alliance with Qiagen to develop a cutting-edge solution portfolio for sample preparation,” Olek added. “While the Qiagen alliance will provide us with robust, reliable and easy-to-use kits for the preparation of clinical samples to enable the actual DNA methylation test, the agreement with Affymetrix now adds the industry standard for DNA analysis. As a result, our customers will get the world’s leading technologies for rapid and reliable DNA methylation analysis.”
“The microarray-based tools and applications in the Powered by Affymetrix program are accelerating the discovery and development of oncology companion and predictive diagnostics in this era of molecular medicine,” said Noel Doheny, Senior Vice President, Molecular Diagnostics at Affymetrix. “We are pleased that another innovator in the diagnostic field like Epigenomics has adopted our proven technology platform for its in vitro diagnostic products.”
Under the Powered by Affymetrix program, companies license technology from Affymetrix to develop innovative microarray products. This includes the GeneChip® System 3000Dx (GCS3000Dx), the first microarray instrumentation system for molecular diagnostic laboratories. The GCS3000Dx has been granted regulatory clearance by the US FDA and is CE marked in the EU for in vitro diagnostic use. The custom-designed technology is being used in many applications, including clinical diagnostics, forensics, animal, industrial and food testing.
Cyprotex launches mechanism-based inhibition of CYPP450 screening
Cyprotex has announced the launch of its new screening service, designed to help drug discovery teams identify compounds that are mechanism-based inhibitors of cytochrome P (CYP)450.
The inhibition of human CYP450s is one of the most common mechanisms that can lead to drug–drug interactions. Metabolic drug–drug interactions, following the coadministration of drugs, can result in either reduced efficacy or increased toxicity. Screening for mechanism-based inhibition of CYP450 earlier in the drug discovery process enables researchers to determine and advance only the compounds that avoid such liabilities, thereby reducing the possibility of costly late-stage failures.
Cyprotex’s Cloe® Screen mechanism-based inhibition assay identifies compounds that are inhibitors of the CYP3A4 isoform, one of the most abundant human CYP450s. By using mass spectrometry as an end point coupled with Cyprotex’s state-of-the-art automation capabilities, the Cloe Screen mechanism-based inhibition assay is a high-quality and cost-effective method that offers rapid turnaround.
The Cloe Screen mechanism-based inhibition assay is a valuable tool in determining drug–drug interactions and complements Cyprotex’s Cloe Screen CYPP450 inhibition range of assays. Further mechanism-based inhibition assays, using other industry-recommended probe substrates, are currently in development at Cyprotex.
Darwin Cheney, Cyprotex’s Chief Scientific Officer, commented on the launch of this new service. “It is well recognized within the pharmaceutical industry that being able to identify safe, efficacious compounds with favorable pharmacokinetic properties, early in the drug discovery process, saves valuable time and money. The high-quality data and rapid turnaround time provided by the Cloe Screen mechanism-based inhibition assay allows researchers to screen early in the drug discovery process, thereby decreasing the likelihood of progressing compounds which have the potential to cause drug–drug interactions.”
Abbott & Cincinnati Children’s Hospital to develop acute kidney failure test
Abbott has signed an exclusive agreement with Cincinnati Children’s Hospital (OH, USA) to develop a urine-based diagnostic assay to detect kidney injury and disease using the protein neutrophil gelatinase-associated lipocalin (NGAL). NGAL is a biomarker that has been reported to be valuable in assisting physicians in rapidly and accurately diagnosing acute kidney failure in a matter of hours, compared with current tests that may take up to several days.
“We are excited to begin our work in developing a test that may help clinicians address kidney failure much earlier and with greater precision,” said William E Brown, Vice President, Diagnostic Assays and Systems Development at Abbott. “When available, this will be an important addition to our menus, and represents the cutting-edge diagnostic science that laboratory customers expect from Abbott.”
Acute kidney failure is present in 5% of all hospital admissions and up to 30% of those patients in intensive care units. When advanced kidney failure is observed in the intensive care unit, mortality rates of 40–80% have been reported. The cost of treating advanced kidney failure in the intensive care unit is US$50,000 per patient.
“Early identification of acute kidney failure is the key to helping physicians manage and treat the condition more effectively,” said Prasad Devarajan, Director of the Division of Nephrology and Hypertension at Cincinnati Children’s Hospital Medical Center. “Developing effective, accurate and reliable diagnostic tests for this condition will significantly improve patient health and lower deaths.”
A study in the April 2005 edition of The Lancet reported that concentrations of NGAL were ‘strikingly raised’ in the urine and serum of children with acute kidney failure after undergoing cardio-pulmonary bypass surgery. In addition, a study published in the May 2006 edition of the American Journal of Transplantation reported that NGAL may be used to predict kidney failure in patients following kidney transplantation.
“The work carried out by Devarajan represents a pioneering effort to move medicine into a more individualized and prospective mode,” said Tom Boat, Chairman of Pediatrics and Director of The Cincinnati Children’s Research Foundation. “Called ‘predictive medicine,’ this approach to care should improve health outcomes and reduce costs by providing critical information in a more timely fashion.”
NGAL is one of several innovative biomarkers that Abbott scientists are working with to develop assays for its analyzers. Abbott is developing automated assays to help physicians diagnose patients with pre-eclampsia and small cell lung cancer. Brown said that Abbott expects to introduce such assays, among others, over the next several years.
LIAI scientists make major finding on potential smallpox treatment
The use of bioinformatics to advance human disease research has received a major boost from researchers at the La Jolla Institute for Allergy & Immunology (LIAI), who have used computational methods to successfully predict immune response to one of the most complex viruses known to man – the vaccinia virus, which is used in the smallpox vaccine. Immune responses, which are essentially how the body fights a disease-causing agent, are a crucial element in vaccine development.
“We are excited because this further validates the important role that bioinformatics can play in the development of diagnostic tools and ultimately vaccines,” said Alessandro Sette, an internationally renowned vaccine expert and head of LIAI’s Emerging Infectious Disease and Biodefense Center. “We have shown that it can successfully reveal, with a very high degree of accuracy, the vast majority of the epitopes that would trigger an effective immune response against a complex pathogen.”
The researchers focused their testing on the major histocompatibility complex (MHC), which binds to certain epitopes and is key to triggering the immune system to attack a virus-infected cell. The scientists were able to identify 95% of the MHC binding epitopes through the computer modeling. “This is the first time that bioinformatics prediction for epitope MHC binding can account for almost all of the (targeted) epitopes that are existing in very complex pathogens like vaccinia,” said LIAI researcher Magdalini Moutaftsi. The LIAI scientists theorize that the bioinformatics prediction approach for epitope MHC binding will be applicable to other viruses.
“The beauty of the virus used for this study is that it is one of the most complex, large viruses that exist,” said Moutaftsi. “If we can predict almost all (targeted) epitopes from such a large virus, then we should be able to do that very easily for less complex viruses like influenza, herpes or even HIV, and eventually apply this methodology to larger microbes such as tuberculosis.”
The big advantage of using bioinformatics to predict immune system targets is that it overcomes the need to manufacture and test large numbers of peptides in the laboratory to find which ones will initiate an immune response.
The LIAI scientific team verified the accuracy of their computer findings by comparing the results against laboratory testing of the peptides and whole infectious virus in mice. “We studied the total response directed against infected cells,” Sette said. “We compared it to the response against the 50 epitopes that had been predicted by the computer. We were pleased to see that our prediction could account for 95% of the total response directed against the virus.”
Genetic parallels found between lung development & lung cancer
Researchers at Children’s Hospital Boston (MA, USA) have demonstrated, through gene chip analyses and bioinformatics techniques, that many genes that are differentially expressed during early embryonic lung development are also differentially expressed in lung cancer.
More importantly, they show that gene expression profiling can predict a lung cancer’s prognosis, and that cancers whose gene expression pattern resembles gene expression during the earliest stages of lung development have the worst prognosis of all.
“This confirms our earlier finding of the importance of normal organ development in understanding cancer,” says Isaac Kohane, Director of the Children’s Hospital Informatics Program (CHIP) and a coauthor on the paper. “Our observations might translate into more accurate prognoses and help us identify mechanisms of cancer growth that can be therapeutically targeted.”
Lung cancer, the world’s leading cause of cancer deaths, has many known subtypes, but it is commonly misclassified, delaying appropriate treatment. In addition, cancers within a subtype may vary in their aggressiveness.
Seeking a better way to classify lung cancers, Hongye Liu and colleagues in the CHIP program examined gene activity in tumors from 186 patients and compared it with the gene activity that occurs during normal embryonic lung development in mice. They also examined 17 samples of normal lung tissue. Starting with 3500 genes known to be common to mice and humans, they identified 596 genes whose activity was altered both in lung tumors and during lung development.
Using the natural trajectory of lung development as a framework, Liu and colleagues were able to predict survival in patients with adenocarcinoma. Tumors with gene expression patterns most like those during very early lung development had the worst prognosis, while tumors with gene expression patterns resembling those seen late in lung development had the best prognosis. Even within a single adenocarcinoma subtype, survival times varied according to gene expression patterns. Gene expression patterns in normal lung tissue resembled those seen late in lung development.
“Before, the idea that cancer and organ development are related was not quantified or statistically significantly demonstrated,” says Liu. “The development perspective gives us a new mechanism for understanding cancer.”
In addition, focusing on the 100 genes with the greatest cancer/development correlation, Liu and colleagues found three groups of genes that are involved in biological pathways believed to be key in lung cancer development, and some of the genes showed potential as drug targets. Several genes had stem cell-like characteristics.
Virginia Bioinformatics Institute launches new simulation software
EML Research and the Virginia Bioinformatics Institute at Virginia Tech have announced the launch of the Complex Pathway Simulator (COPASI) simulation software. COPASI is a major software package that allows users to model, simulate and analyze biochemical and systems biology networks.
COPASI, which supports the Systems Biology Markup Language (SBML) standard for systems biology software, enables researchers to investigate how a system is working by allowing them to construct biochemical models, reproduce experimental results and justify the validity of the chosen model. The software may be freely downloaded on the COPASI website for noncommercial purposes.
“The first official release of COPASI represents a key milestone in delivering a fully comprehensive software solution for modeling and simulation to the life science community,” remarked Pedro Mendes, Associate Professor at Virginia Bioinformatics Institute. “We have been working closely with Ursula Kummer’s group at EML Research to deliver an open-source software package that aids in the understanding of cellular and molecular behavior and which facilitates the quantitative interpretation of modern experiments. COPASI is the culmination of 6 years of intense development work to deliver a package that meets the real needs of life scientists. The future development of COPASI will continue to strive towards providing a powerful package that every biologist can use, not just experts in systems biology.”
COPASI simplifies the task of model building by assisting the user in translating the language of chemistry (reactions) to mathematics (matrices and differential equations). The user-friendly interface is combined with a set of sophisticated numerical algorithms that assure the results are obtained quickly and accurately. COPASI simulates the kinetics of systems of biochemical reactions and provides a number of tools to fit models to data, optimize any function of the model, perform metabolic control analysis and linear stability analysis.
“Simulation and modeling are becoming increasingly important tools in systems biology research and can be used to test the physical and chemical limitations, as well as feasibility, of a wide range of biochemical reactions. We anticipate that COPASI will prove invaluable to researchers not only in simulating increasingly complex networks but also in helping to understand how external factors, for example drugs, impact metabolic systems,” commented Ursula Kummer, Principal Investigator at EML Research. “We have already seen many applications from our existing user community and expect many more due to COPASI’s inherent flexibility for top-down and bottom- up modeling.”
GeneGo & Elsevier MDL provide access to compound databases, patents, literature & pathways
GeneGo, Inc., a leading provider of software and databases for systems biology and pathway analysis, and Elsevier MDL, a leading provider of scientific content, informatics framework and workflow applications for pharmaceutical research, have announced a collaboration. The latest version of GeneGo’s data-mining platform MetaCore 4.0 will be seamlessly integrated with the MDL® suite of databases via the DiscoveryGate® content platform. Researchers will be able to identify drug targets and bioactive compounds via pathway analysis and retrieve comprehensive information on their synthesis, biological effects, commercial availability and relevant literature within one application.
“The integration of MDL databases with GeneGo’s pathways information systems enables scientists to bridge the gap between cell biology and organic chemistry,” comments Steve Young, Director of MDL Content Strategy. “For the first time, biologists will be able to quickly review cheminformatics data of small molecules involved in biological pathways and chemists will be able to view molecular pathway information related to their lead compounds.”
“Lately, a number of customers approached us with requests for functional analysis of the effects of drug-like compounds rather than genomic data,” says Julie Bryant, Vice President, Business Development at GeneGo. “Although pathways and network analysis of bioactive compounds is a common practice in MetaCore, we partnered with Elsevier MDL for in-depth coverage of literature and patent-derived information relevant for compounds. We are very pleased to be working with Elsevier MDL, the market leader in medicinal chemistry knowledge databases, Integration with the Elsevier MDL chemistry space opens up new applications for our products in medicinal chemistry, including high-throughput and high-content screening, hit selection and validation, lead development programs and chemogenomics.”
Thermo Electron acquires GV Instruments
Thermo Electron Corp., the world-leader in analytical instruments, has acquired GV Instruments Ltd (Manchester, UK), a manufacturer of isotope ratio mass spectrometers (IRMS), for approximately US$21 million (£11.6 million), subject to a postclosing adjustment. The acquisition enables Thermo, already a leading IRMS manufacturer, to offer additional solutions in high-precision isotope ratio determination used in earth sciences, and medical and life sciences applications. In particular, GV Instruments will add the capability of noble gas isotope mass spectrometry to Thermo’s product offering for use in climate research, food and flavor analysis for origin and authenticity, and agriculture research, as well as medical and life sciences research and analysis.
“By adding the complementary range of products from GV Instruments, Thermo can now offer the most sophisticated IRMS solutions to a variety of significant fields of earth science research such as geochemistry, geochronology and climate research, just to name a few,” said Marijn E Dekkers, President and Chief Executive Officer of Thermo Electron. “Additionally, GV Instruments’ customers will have access to Thermo’s global presence and world-class customer support.”