Bio Saga Blog - A Chronicle of Life Sciences & Informatics

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Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base–driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis. Do you wish to know more?

Elsevier, a world-leading provider of scientific, technical, and medical information products and services, announced today the acquisition of the business assets of  Ariadne Genomics , a provider of pathway analysis tools and semantic technologies for life science researchers. Ariadne will be integrated with Elsevier's Corporate Markets division. "Ariadne Genomics' pathway analysis tools and semantic technologies integrate research findings from across multiple content sources providing a deeper understanding of biological pathways and disease progression. Ariadne's products improve research productivity and outcomes for life science researchers by delivering new insights for potential interventions, therapies and cures," said Alexander van Boetzelaer, Managing Director of Elsevier Corporate Markets. "Ariadne brings to Elsevier an information offering in the biology domain and a passionate and dedicated team of life science professionals. Ariadne's team ...

Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, as well as graphics processing unit (GPU)-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 “avian” and H1N1pdm “swine” flu N1-subtype neuraminidases. The simulations reveal an electrostatic binding funnel that plays a key role in directing oseltamivir into and out of its binding site on N1 neuraminidase. The binding pathway for oseltamivir suggests how mutations disrupt drug binding and how new drugs may circumve...

This something really interesting to PPI, Systems biology  and molecular networks people, I just recently came across, Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways.  Results: We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them t...

Through a complex analysis of protein interactions, researchers from IRB Barcelona and the Joint Programme IRB-BSC have discovered new molecular mechanisms that may be involved in the development of Alzheimer’s disease. The study, a collaboration between bioinformaticians and cell biologists, was led by IRB Barcelona group leader and ICREA researcher Patrick Aloy and appears today in the Genome Research, a reference journal in the field of genomics. Alzheimer’s disease is an age-related neurodegenerative disease. Despite the considerable efforts made in recent years to understand the mechanisms that trigger this disease, an effective treatment is not yet available. This study reveals new molecular and functional data that could help researchers gain a better understanding of the disease and potentially to develop new therapies.  From the computer to the lab  Proteins are the molecular instruments that cells use to carry out their functions. Proteins don’t normally act alone,...

Thomson Reuters today announced that it has acquired GeneGo, a leading provider of biology and disease information, analytics, and decision support solutions for pharmaceutical research and development. Effective immediately, GeneGo will become part of the Healthcare & Science business of Thomson Reuters. Financial terms of the transaction were not disclosed. The acquisition enables Thomson Reuters to provide the pharmaceutical, biotechnology, and academic research communities with solutions that provide better understanding of the underlying mechanism of disease and potential therapies. GeneGo’s scientific expertise and assets in biology-driven drug discovery complement the Thomson Reuters life sciences portfolio that covers drug pipeline competitive intelligence, patents, and chemistry. do you wish to know more?

GeneGo today said that Agilent's GeneSpring bioinformatics solution has been integrated with GeneGo's MetaCore. The collaboration was announced in connection with the newest version of Agilent's GeneSpring. Agilent said today introduced GeneSpring GX 11.5, which can interpret microarray, proteomics, and metabolomics experiments together for the first time. The newest version includes a direct connection to the MetaCore pathway analysis engine, enabling users to seamlessly upload expression data analyzed in GeneSpring, said GeneGo. "MetaCore can concurrently visualize multiple types of data and will be able to take advantage of this new functionality in GeneSpring which will be very helpful to our joint customers," Julie Bryant, VP of business development for St. Joseph, Mich.-based GeneGo, said in a statement.

Genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) have consistently observed strong evidence of association with polymorphisms in   APOE . However, until recently, variants at few other loci with statistically significant associations have replicated across studies. The present study combines data on 483,399 single nucleotide polymorphisms (SNPs) from a previously reported GWAS of 492 LOAD cases and 496 controls and from an independent set of 439 LOAD cases and 608 controls to strengthen power to identify novel genetic association signals.   Studies looking for genetic variants across the genome that affect late-onset Alzheimer disease (LOAD) have had little success identifying genes other than  APOE . Here, we use an expanded set of AD cases and controls to improve our power to detect genetic variants driving LOAD risk. Analyzing 483,399 genetic variants across the genome in a discovery dataset of 931 cases and 1,104 controls, we found a s...

This Pathways Compendium provides an index of Alzheimer disease pathway models contributed by researchers and companies. Probable Interaction Networks Involved in Pathology of Alzheimer Disease: Predicting Targets and Therapeutic Agents - NetPro™ based Study . Developed by researchers at Molecular Connections Private Limited, an in silico discovery services company. Users can click on a specific node (molecule) to get information on all interactions of the molecule in the given network. Click on the interaction arrows for information on the specific interaction. The Alzheimer Research Forum is a Pioneering Biomedical Web Community . Founded 13 years ago when the Web was still in its infancy, the "Alzforum" has more than 5,000 registered members and is familiar to most Alzheimer scientists in the world. XTractor Premium - A Platform for discovery , knowledge sharing, analysis and modelling of published biomedical facts. The only Knowledgebase which provides "manu...

More good news for Bio, more so for Bioinfo & CompBio while the end of Jyly say House Passes Proposed 3 Percent NIH Funding Increase now NIH is really promoting Bio Science research to bring in a economic turn. The best of times is now ! A National Institutes of Health funding program will support exploratory research and development projects in informatics and computational biology that explore a range of areas, including genomics , medical genetics, proteomics , biomedical imaging, and a wide variety of other approaches. Funded through the National Cancer Institute, the National Human Genome Research Institute, the other centers across NIH, the " Exploratory Innovations in Biomedical Computational Science and Technology " program will be coordinated by the NIH Biomedical Information Science and Technology Initiative committee. Under the program, NIH will grant up to $275,000 over two years to academic institutes, small businesses, non-profits, state governments, ...

BANGALORE, Indian Researchers have achieved a breakthrough, identifying a protein pathway that triggers cancer in the human body owing to its erratic behaviour. Researchers at Bangalore’s National Centre for Biological Sciences (NCBS) led by Satyajit Mayor and Neha Vyas have identified what is known as the Hedgehog pathway and the ways in which it forms and leads to cancer. The researchers, who have published their work in the journal, Cell, say this pathway is formed when the proteins (called hedgehog), which are separate, get drawn to each other by electrostatic interactions between amino acids present around the proteins. A small cluster of proteins then gets formed and goes on to form a mega-cluster. This travels to other cells and creates effects that are good or bad — the cluster could be normal and help organ regeneration or tissue repair, or the cluster could get hyperactive and affect other cells, which is the sign that cancer is coming. Simply put, the NCBS research indicates...

New preclinical research shows that cannabinoid cell surface receptor CB1 plays a tumor-suppressing role in human colorectal cancer, scientists report in the Aug. 1 edition of the journal Cancer Research. Endocannabinoid signaling is important to the normal functioning of the digestive system and has been shown to protect the colon against inflammation. Since chronic inflammation is a known risk factor for colorectal cancer, the researchers decided to look into the role of cannabinoid receptors in a mouse model of colon cancer. Cannabinoids previously had been shown to kill cancer cells in lab experiments by inducing apoptosis - programmed cell death. The team confirmed the role of CB1 in apoptosis, showing that tumor cells with high CB1 expression were sensitive to apoptosis when treated by a cannabinoid agonist. Cell lines with silenced CB1 resisted cell death. A series of experiments showed that CB1 increases cancer cell death by stifling a protein called survivin. Survivin is ov...

In their current study, published in the online edition of the journal Nature , Conboy and her team found that old muscle produces elevated levels of a molecule called TGF-beta, which is known to inhibit muscle growth. The researchers then showed that the muscle-deteriorating effects of TGF-beta can be reversed by blocking its pathway in old mice. In the experiments, the researchers used RNA interference, which can silence specific genes, to inhibit the molecules that act downstream of TGF-beta to prevent cells from multiplying. They then locally injured the muscles of treated mice, as well as untreated old and young mice, by injecting a small amount of snake venom, which killed muscle tissue in the immediate vicinity. After five days, the team found that the young mice were able to produce healthy cells to replace damaged tissue. The treated older mice, whose inhibitory pathways were suppressed, were able to regenerate new cells in much the same way. Not surprisingly, old untreate...

Previously blogging on novel anti-cancer molecules in Researchers Find that a Small Molecule Can Activate an Important Cancer Suppressor Gene. Scientists at The Wistar Institute have developed a new type of enzyme inhibitor capable of blocking a biochemical pathway that plays a key role in cancer development by combining natural organic atoms with metal complexes. Based on studies in human melanoma cells, the research paves the way for developing new ways to treat cancer by dampening the overactive enzyme activity that leads to uncontrolled tumor growth. Details of the study, to be published in the May 16 issue of the journal ACS Chemical Biology , show how small-molecule inhibitors can be designed to target a family of signaling proteins, called phosphatidyl-inositol-3-kinases, or PI3Ks. “The PI3K pathway has been called the most mutated pathway in human cancer,” says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and s...