Bio Saga Blog - A Chronicle of Life Sciences & Informatics

By considering sequence data for individuals assessed through the 1000 Genomes Project, a team led by researchers from Yale University and Wellcome Trust Sanger Institute came up with a computational method for prioritizing potential disease culprits — including those in non-protein-coding parts of the genome. As they reported online today in Science , the researchers sifted through SNP profiles in coding and non-coding sequences in 1,092 genomes, focusing on functionally annotated areas. With the help of information from the ENCODE project, mutation databases, and other data sources, they narrowed in on sequences that seem especially sensitive to change. The group tapped these mutation-sensitive sites to develop an approach called FunSeq, which proved useful for uncovering new apparent driver mutations using sequences from around 90 cancer genomes. These included almost 100 driver candidates in non-coding sequences, according to study authors, who noted that FunSeq is expected...

The nonprofit ECRI Institute has released a BRCA testing information guide for patients interested in learning more about the genetic risk of hereditary breast and ovarian cancer. The guide comes in response to the growing concern and questions among women about the information their genes contain about the risk for cancer, after actress Angelina Jolie wrote an op-ed piece discussing her decision to get a double mastectomy as a result of carrying a BRCA1 mutation associated with heightened risk of hereditary breast and ovarian cancer. There are reports that Jolie's highly publicized and controversial decision has caused a spike among women asking their physicians for BRCA testing. "People can get caught up in the headlines, which can lead to quick, uninformed decisions," says Vivian Coates, VP of information services and health technology assessment at ECRI Institute, in a statement. "Many women may find that after talking to their physicians about their ris...

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...

Mutations in the protein tyrosine kinase gene ERBB4 contribute to — and may provide hints about treating — a subset of melanoma, according to a paper by researchers from the National Institutes of Health and Johns Hopkins University that appeared in the advanced, online edition of Nature Genetics this week. The team sequenced protein tyrosine kinase or PTK genes in 29 individuals with melanoma. Their search uncovered dozens of somatic mutations affecting the kinase domain of 19 different PTK genes. When they looked at the same 19 genes in another 79 melanoma patients, the researchers found that almost a fifth of those tested harbored mutations in ERBB4 . And, they reported, knocking down the mutated form of ERBB4 or using a drug that targeted the gene slowed the growth of melanoma cell lines, suggesting it might be useful to evaluate ERBB4 status in melanoma patients. Researchers at the NIH Intramural Sequencing Center sequenced all 86 PTK family genes in tumor samples from 29 ...

Last week the XTractor Premium Knowledgebase has clocked 150,000 manually categorized biomedical facts. The knowledgebase currently grows at a rate of more than 700 facts every single day from PubMed and covers information on Biomarkers , Disease mechanisms, Clinical Trials, polymorphisms , mutations , knockouts and pathways . The knowledgebase recently crossed landmark of more 10000 relationships on knockout and mutation studies alone in XTractor. Knockout/Knockdown related facts: 10132 Mutation related facts: 14331 So not only you get the most relavant scientific facts everyday but also individual uptodate knowledge on knockouts, mutations, biomarkers , SNP and so on… XTractor Premium - A Platform for discovery , analysis and modelling of published biomedical facts. The only Knowledgebase which provides "manually" annotated facts from PubMed on a weekly basis Innovative Features like Semantic Search , Concept Linking , Bibliographic search , Save, Export a...