Singapore Attracts Life Science Companies

Today, Singapore continues to capitalize on its geographic location as one of the crossroads of the world to grow life science companies. About 70 airlines serve Singapore, making it a gateway to Southeast Asia.

As a testament to their commitment to the life science industry in the 21st century, Singapore built two state-of-the-art biomedical research parks. The Biopolis, a biomedical research complex of seven buildings that houses 2,000 scientists, opened in September 2003.

The first tenants were the Genome Institute of Singapore and the Bioinformatics Institute. Buildings named Centros, Genome, Matrix, Nanos, and Proteos hold biomedical research institutes of the Agency for Science Technology and Research (A*STAR), which oversees scientific efforts under the Ministry of Trade and Industry.

The Biopolis tenants share high-quality technical services, such as DNA sequencing, proteomics, NMR, and FACS (flow activated cell sorting) facilities.

The Biomedical Sciences group of Singapore's Economic Development Board, Bio*One Capital, and A*STAR work in close partnership to develop, fund, and build life science companies and facilities. The joint initiative, launched in 2000, is paying off. Between 2003 and 2004, manufacturing output in the biomedical sciences sector rose 33%, and employment grew 7% to 9,225 workers.

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Novel therapies for age-related diseases such as Alzheimer's and Parkinson's

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 untreated mice did not recover as well and developed fibroblasts and scar tissue around the injured site.

Reading Between Lines

In the series of blogs on the aftermath of GINA, first it was the consumers GINA Aftermath - Consumers Still Wary of Genetic Tests and now its the turn of the firms Gene Testing Questioned by Regulators , Consumer Genomics Firms Confused by California's Actions; State Seeks Federal Solution be is consumer or the firm no body is spared, as President Bush often quips "justice is served" and all are same in the eyes of Democracy. Well will Mr.Governor Arnold Schwarzenegger come up with a quick solution for this?

CRANKITE: A fast polypeptide backbone conformation sampler

Background: CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details. Methods: In contrast to other programs relying on local Metropolis moves in the space of dihedral angles, our sampler utilizes local crankshaft rotations of rigid peptide bonds in Cartesian space. Results: The sampler allows fast simulation and analysis of secondary structure formation and conformational changes for proteins of average length.

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The new beta version of UniProt

Recently took a peek at the new version of UniProt. It has some exciting features on customized searches, filtering results using key words, customize the results view and cross references to Public databases including the 3D- viewers. Try taking the SITE tour on the right hand side panel. http://beta.uniprot.org. This is a beta version of the their new web site, most welcome to give your feedback. Please take into account that some functions are incomplete and many help pages are still preliminary. beta.uniprot.org

Roche Acquires Early-Stage Cancer Drug In US$778mn Deal

In keeping with Roche's commitment to developing cancer therapies, the company has acquired worldwide exclusive rights to an early stage cancer therapy that is being co-developed by Belgian biopharmaceutical firm Thrombogenics and Swedish antibody developer BioInvent. Under the agreement the two companies will share an upfront payment of EUR50mn (US$78mn) plus up to EUR450mn (US$700mn) based on reaching pre-agreed milestones. The two companies will also receive royalties from eventual product sales, with a 60% share for Thrombogenics and 40% going to BioInvent. The two original developers have retained a co-promotion option covering the Benelux, Nordic and Baltic

Controlling HIV Evolution

Dr. Ronald Collman talks about exciting new discoveries on HIV, the virus that has taken 25 million lives. Dr. Ronald Collman, professor of medicine in microbiology, virus/cell/molecular core director, Penn Center for AIDS Research, University of Pennsylvania.He describes the molecular structure, pathology, and with great insight, the incredible discoveries that might just help us conquer HIV.
Listen to the Original audio source

In Silico Transfer of Neurotransmitter Transporter Motif Between Structurally Analogous Protein (Catechol-O-methyltransferase)

Here is a abstract that i had submitted at the 3D sig:Structral Bioinformatics at the 1st Structural Bioinformatics Meeting at ISMB 29-30 July 2004, Glasgow, Scotland, UK. I do not know how relevant is the issue to this day. I am interested in working further in this area and i am interested in collaborating. Do let me know your comments also pour your suggestions on how to further this study.

In silico methods can be used to design protein, based on stability and functionality using computational methods rather than laboratory procedures (Comet et al., 2000). The changes taking place due to the transfer of motif region from human Catechol-O-methyltansferase to rat Catechol-O-methyltransferase can be studied effectively using computational methods. This will provide insight for further development of the study about the function of neurotransmitter region of catechol-O-methyltransferase and its involvement in the Parkinson’s disease.

Catechol-O-methyltransferase (COMT) catalyzes the transfer of the active methyl group from S-adenosyl-L-methionine to the two ring hydroxyl groups of catechols (Garnier et al., 1978). The main function of COMT involves the elimination of biologically active or toxic catechols and their metabolites. COMT may modulate the neurotransmitter function of dopamine and norepinephrine in various mental processes through altering the rate of their metabolic inactivation in different parts of the brain.

COMT is found both in membrane bound form in post synaptic neurons and in cytoplasmic soluble form in the extraneuronal tissue like glial cells.

The sequence of the Human COMT was retrieved from Human Protein Reference Database (HPRD). The BLAST and ClustalW was performed to confirm the homologous sequence for human COMT as rat COMT seq. The motif sequence was identified from the Blocks searcher. PDB BLAST confirmed rat COMT as the structural homology for modeling the structure of human COMT using SWISSMODEL. The human sequence contained VLLELGAYCGYSAVRMA in the neurotransmitter motif sequence. But some organism and rat posses neurotransmitter sequence with the change in the two amino acid val and leu (LVLELGAYCGYSAVRMA)

An initial model of COMT of human was generated through the on-line automated comparative protein modeling server, SWISSMODEL (Guex,N., Peitsch, M.C.1997). and was verified to evaluate the quality of the structure.

SAVS, a Structure Analysis and Verification Server was used to study the quality of the model structure generated by SWISSMODEL (Van G.W. 1996). The overall quality factor of the model was 96.429* and the 98.31* of the residues had an average 3D-ID score >0.2.
The in silico transfer was done with the help of SwissPDB viewer mutation tool. The structure of the mutated rat sequence was compared with original rat COMT structure. This may give us information about changes involved after the mutation and these changes may in turn affect the functions of the animal.

The results from both Expasy tools and Predict Protein states that there is very less difference in the % composition of the secondary structures of both the sequences. These results infer that the mutated rat with the human motif sequences may also poses the same functionality and stability as that of the original rat COMT sequence.

References:
Combet C., Blanchet C., Geourjon C. and Deléage G., 2000 March, TIBS Vol. 25, No 3 [291]:147-150

Garnier J, Osguthorpe DJ, Robson B., 1978, Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. Vol. 120, pp. no 97-120.

Guex,N., Peitsch,M.C. (1997). SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18, 2714-2723.

Van Gunsteren, W., 1996, Biomolecular Simulations: The GROMOS96 Manual and User Guide. VdF Hochschulverlag ETHZ.

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XTRACTOR™ Data Mining Simplified

The first of its kind - SCIENTIFIC LITERATURE alert service which also provides manually annotated sentences for the keywords of YOUR preference

• Highly accurate, manually annotated sentences for given keywords.
• Daily scientific literature updates at your desktop along with extracted facts - manually curated.
• Provision to change keywords with your changing research preferences.
• Annotated sentences and abstracts get stored in your profile, as and when they get updated in PubMed.
• Classify and create your own datasets of annotated facts.
• Enhanced experiences of reading & analyzing literature.
• Access your profile / datasets from anytime, anywhere.
• Discover and Create newer relations from scientific facts classified by the XTractor™ Community.
• Tag your favorite abstracts and share them across other users.
• Much more faster and an Absolutely Free Service

PRODUCT HIGHLIGHTS

Abstract Summarization
The XTractor™ system would provide extracted relations in addition to identifying the abstracts of subscriber's interest. Our experience suggests time required for summarization of an abstract is the greatest as the user needs to understand the context, analyze the content and make sense of the relation followed by extraction. So not only the abstracts would be prioritized and delivered to the subscriber but also sentences, which are extracted and processed manually.

Categorization
Categorization involves tagging the extracted sentences to most popular ontology(s) in biology and chemical spaces. XTractor™ would ensure highly accurate (manual curation) in all its annotation efforts be it genes, processes or drug names, all mapped to their relevant ontology(s). So you need not work again on reclassification of sentences or facts to accurate ontology(s).

Topic Tracking
XTractor™ provides updates to the subscribers on a daily basis based on topic tracking in PubMed. The service allows the user to Key in the Keywords of interest and notifies them via email when new articles get published in PubMed. Unlike the other free NLP utilities that are available, Molecular Connections would be using its skilled scientists to validate the data.

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GINA Aftermath - Consumers Still Wary of Genetic Tests

Previously blogging on GINA Dawn of the GATTACA era! now Industry Survey Shows: The surveyors found that only five percent of consumers said that they were “very likely” to take a disease-specific genetic test in the next few years, and 15 percent said they would be “likely” to take one.

A total of 35 percent said that they would not submit to genetic tests, with 14 percent citing concerns about privacy, 5 percent saying they would not want to know about the results of their tests, and 16 percent saying both reasons would compel them to avoid genetic tests.

Although more than 50 percent of those who responded said that they are concerned about getting cancer or heart disease, only 4 percent of those said they had taken a genetic test for a particular disease. Two-thirds of those who did have a genetic test were advised to do so by a doctor.

The respondents had about the same comfort level of sharing genetic information with their spouses or partners as with their doctors, 72 percent and 71 percent respectively.

Only 22 percent of those who responded were comfortable with sharing results from genetic tests with institutions for research purposes, and almost none would give up that information to health insurance companies (3 percent), and even less to employers (2 percent) and prospective employers (1 percent).

From these findings, it is concluded that “makers of these tests might have more success penetrating the market by working through doctors rather than trying to make the case for their products directly to the consumer.”

The company said “The Personalized Medicine and Wellness Survey” is the first of a three-part study on the subject that will be released sometime this summer.

Boehringer Ingelheim to Acquire Actimis Pharmaceuticals for $515M

Boehringer Ingelheim will acquire Actimis Pharmaceuticals through a structured buyout in which Boehringer Ingelheim will acquire shares of Actimis depending on the achievement of several successive milestones with Actimis’ leading asthma compound AP768.

If AP768, currently in Phase I development, is successfully advanced into a Phase III, Boehringer Ingelheim will own 100% of Actimis’ shares. Upon successful completion of the entire development program, the total deal will be worth $515 million.

AP768 interacts with CRTH21, a target for asthma and allergic rhinitis. Previous to the currently ongoing Phase I trial, the compound was shown to have a more effective mechanism of action across multiple available animal models compared to currently marketed leukotriene receptor antagonists, according to the companies.

CoMet' – a tool to study the integrated machinery of cell and predicts components that effect cancer

A new computer-based method of analyzing cellular activity has correctly predicted the anti-tumour activity of several molecules. Research published today in BioMed Central's open access journal Molecular Cancer describes 'CoMet' – a tool that studies the integrated machinery of the cell and predicts those components that will have an effect on cancer. Jeffrey Skolnick, in collaboration with John McDonald, led a team from the Georgia Institute of Technology who have developed this new strategy. As Skolnick explains, "This opens up the possibility of novel therapeutics for cancer and develops our understanding of why such metabolites work. CoMet provides a deeper understanding of the molecular mechanisms of cancer".

Identification of metabolites with anticancer properties by Computational Metabolomics

The small molecules that are naturally produced in cells are called metabolites. Enzymes, the biological catalysts that produce and consume these metabolites are created according to a cell's genetic blueprints. Importantly, however, the metabolites can also affect the expression of genes. According to the authors "By comparing the gene expression levels of cancer cells relative to normal cells and converting that information into the enzymes that produce metabolites, CoMet predicts metabolites that have lower concentrations in cancer relative to normal cells".

The research proves that by adding such putatively depleted metabolites to cancer cells, they exhibit anticancer properties. In this case, growth of leukemia cells was slowed by all nine of the metabolites suggested by CoMet. The future for this treatment looks bright, in McDonald's words, "While we have only performed cell proliferation assays, it is reasonable to speculate that some metabolites may also exhibit many other anticancer properties. These could be important steps on the road to a cure".

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Researchers create molecule that nudges nerve stem cells to mature

The last time i blogged on stem cells it was rather about a challenge in Fresh hurdle for stem cell hunt, but this time its more on a positive note and fairly quite an interesting and welcome news... a SERENDIPITY!

Inspired by a chance discovery during another experiment, researchers at UT Southwestern Medical Center have created a small molecule that stimulates nerve stem cells to begin maturing into nerve cells in culture.

"This provides a critical starting point for neuro-regenerative medicine and brain cancer chemotherapy," said Dr. Jenny Hsieh, assistant professor of molecular biology and senior author of the paper, Small-molecule activation of neuronal cell fate, Jay W Schneider, Zhengliang Gao, Shijie Li, Midhat Farooqi, Tie-Shan Tang, Ilya Bezprozvanny, Doug E Frantz, Jenny Hsieh
SUMMARY: We probed an epigenetic regulatory path from small molecule to neuronal gene activation. Isoxazole small molecules triggered robust neuronal differentiation in adult neural stem.
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Some people never learn: the genetics of learning from our mistakes

In its simplest sense, we imagine that learning occurs through a series of positive and negative rewards. Some actions lead to pleasure, others to pain, and it seems reasonable to expect that people will repeat the actions with pleasurable results and avoid those that ended in pain. Yet, we all know people who aren't deterred by the idea of punishment. We all know people who never seem to learn.

Could there be a physical reason, hidden in their genes?

Read the rest of this post... | Read the comments on this post......more

Klein, T. (2007). Genetically Determined Differences in Learning from Errors. Science, 318(5856), 1642-1645.

Genome Viewers/Editors - Three of the Best

A number of online and offline genome are viewers available, each with it’s own set of pros and cons. Here is an overview three.

Artemis

Artemis is a genome viewer available from Sanger Institute. Its a java based tool with a 3-paned interface window that depicts the genome at various resolutions. Alternating between the different resolutions is a bit tricky but once you get a hold of it shouldn’t be difficult. There is a also search tool that allows your to track down the particular feature that you’re looking for.

A great feature of Artemis is that it allows you to edit the sequence annotations and features. Although the tool isn’t perfect and is a bit finicky at times, it gets the job done.

Artemis supports the most common filetypes -EMBL, GENBANK, FASTA or raw format. Extra sequence features can be added in in EMBL, GENBANK or GFF format.

The best thing I like about Artemis is that there is a web version as well as an offline version, which means once you get used to it you can run it on or offline on any computer anywhere that has java.

Apollo

Apollo genome viewer is another java based genome viewer and annotation tool. It is a part of the Gmod project which runs most of the online genome viewers. The tool came out of a collaboration between the Berkeley Drosophila Genome Project and The Sanger Institute.

Apollo has a similar set of features to Artemis provides, but I found the interface to be less user-friendly. But that’s just a personal opinion so you would be best to have a go at using both Artemis and Apollo and decide for yourself which is best. Again, the user guide will help you make best use of Apollo.

The NCBI Genome Workbench

The NCBI Genome Workbench is far more than just a genome viewer. As the name suggests, it is a complete and customizable workbench of tools that allow you to organize sequence data, which you can retrieve from NCBI databases or from your own files, for a project then view and manipulate them in a variety of ways. There is no online version available but downloading and installing NCBI genome workbench is quite simple.

The software allows you to view sequences as flat sequence files, phylogenetic trees, alignments and more.

The excellent zoomable graphics mode is the real strength of this package. It allows you to easily explore your sequence data at different levels of detail - individual genes can be viewed alone or in their genomic context and can be BLASTed straight from the graphical view. A nice set of alignment analysis tools is also available and BLAST and analysis results can be saved to your project making this a great way to keep track of your sequence data and analyses.

The tool supports quite a number of file formats, and I had no problems working with FASTA and most other file formats however when I tried to import the complete 1st chromosome of Dicyostelium which is in a GFF3 format the program kept crashing repeatedly, so clearly some bugs still need to be ironed out.

The NCBI genome workbench is a great idea, and provides a number of useful tools that make the program a must-have but the interface is a bit clunky and takes some getting used to. However, the site has a comprehensive set of instructions/tutorials to help you get up the learning curve quickly.

Facebook Applications for Biologists

If you love spending time on Facebook, but want to keep on working while “Facebooking” (or whatever the correct verb is) don’t fear. Here are 4 (5) biology-related Facebook applications, most of which you can claim to be working while using.

F@H Protein Researcher Folding@Home (F@H) is a distributed computing project where individuals allow their free CPU time to create a world-wide super-computer that is used for the study of protein folding. The Protein Researcher Facebook application tracks user statistics for the F&H and includes team pages/walls, a profile box with your individual statistics, and ranked standings.

SciBook - Science Social Network SciBook is a Life science social network for scientists. It’s a way for scientists to add the publications they are reading or have successfully published to their profile and discover others on Facebook interested in the same papers.

Latest PHD Comics This application puts PHD comics on your profile. It updates automatically, so you don’t have to keep checking the website for new comics

Pubface. This application allows you to search pubmed directly from Facebook. It also has a tell-a-friend feature, where you can forward interesting papers onto your friends, and a library feature that allows you to store up to 300 articles. I’m not really sure why you’d want to search Pubmed from a social networking site but who am I to judge? Another application - PubMed Search - does a similar job


Be a part of the XTractor community. XTractor is the first of its kind - Literature alert service, that provides manually curated and annotated sentences for the Keywords of user preference. XTractor maps the extracted entities (genes, processes, drugs, diseases etc) to multiple ontologies and enables customized report generation. With XTractor the sentences are categorized into biological significant relationships and it also provides the user with the ability to create his own database for a set of Key terms. Also the user could change the Keywords of preference from time to time, with changing research needs. The categorized sentences could then be tagged and shared across multiple users. Thus XTractor proves to be a platform for getting real-time highly accurate data along with the ability to Share and collaborate.

Sign up it's free, and takes less than a minute. Just click here:www.xtractor.in.

PURE: a webserver for the prediction of domains in unassigned regions in proteins

Protein domains are the structural and functional units of proteins. The ability to parse proteins into different domains is important for effective classification, understanding of protein structure, function, and evolution and is hence biologically relevant. Several computational methods are available to identify domains in the sequence. Domain finding algorithms often employ stringent thresholds to recognize sequence domains. Identification of additional domains can be tedious involving intense computation and manual intervention but can lead to better understanding of overall biological function. In this context, the problem of identifying new domains in the unassigned regions of a protein sequence assumes a crucial importance.

Accumulation of domain information of sequence homologues can substantially aid prediction of new domains. In this paper, we propose a computationally intensive, multi-step bioinformatics protocol as a web server named as PURE (Prediction of Unassigned REgions in proteins) for the detailed examination of stretches of unassigned regions in proteins. Query sequence is processed using different automated filtering steps based on length, presence of coiled-coil regions, transmembrane regions, homologous sequences and percentage of secondary structure content. Later, the filtered sequence segments and their sequence homologues are fed to PSI-BLAST, cd-hit and Hmmpfam. Data from the various programs are integrated and information regarding the probable domains predicted from the sequence is reported.

PURE protocol as a web server for rapid and comprehensive analysis of unassigned regions in the proteins. This server integrates data from different programs and provides information about the domains encoded in the unassigned regions.

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Protein Linked To Alzheimer's Disease Also Has Role In HIV Progression

A protein related to heart disease and Alzheimer's is found to be a factor in HIV. The apolipoprotein (apo) E4 isoform has been implicated in neurodegeneration in Alzheimer's disease, cardiovascular disease, and stroke. Now, investigators at the Gladstone Institutes, the University of California, San Francisco, the University of Texas Health Science Center at San Antonio, and the Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, Maryland have shown that this troubling protein is a risk factor for AIDS progression rates and promotes entry of HIV into cells.

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Crystal structure errors — in CSD too

Many of you involved in structure based drug discovery will know very well about the numerous problems and errors in the data found in the Protein Data Bank (PDB) especially concerning the ligand structures. There have been a lot of publications about such errors, e.g. in Jones et al. J Mol. Biol. (1997) 267:727, and I heard various conference presentations about this topic too, e.g. by Gerard Kleywegt (University of Uppsala), titled “Protein crystallography: not as simple as ABC then?” at Bryn Mawr, Philadelphia (15-19 October 2007) eChemInfo meeting. The errors are often blamed on the low resolution of the structures involving large protein structures (often thousands of atoms). One would assume that the small molecule crystal structures of the Cambridge Structural Database (CSD) do not have such errors, since they have much higher resolution and dealing with small molecules. Let me correct that wrong assumption!

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New target to enhance anti-cancer drug sensitivity found in translation

Several times i have discussed the the topic of anti-cancer targets, Novel Enzyme Inhibitor Paves Way for New Cancer Drug: Agent Proves Effective Against Melanoma Cells; Researchers Find that a Small Molecule Can Activate an Important Cancer Suppressor Gene. The development of resistance to anticancer chemotherapeutic agents remains a large problem. In some cases, such resistance is associated with altered control of a cellular process known as translation, which is central to the generation of proteins. New data, generated by Jerry Pelletier and colleagues, at McGill University, Montreal, have identified a drug that can enhance the sensitivity of mouse cancer cells to standard anticancer chemotherapeutic agents. In the study, small molecules were screened for their ability to inhibit the initiation of translation by modifying the function of a protein known as eIF4A, which has a central role in translation initiation. A class of natural drugs known as cyclopenta[b]benzofuran flavaglines were found to have the desired effects and one member of this class of compounds was shown to reverse the resistance of cancer cells to anticancer chemotherapeutic agents in a mouse model of lymphoma. The authors therefore suggest that developing approaches to inhibit translation initiation by targeting eIF4A might provide a way to altering drug resistance in cancers exhibiting altered control of translation initiation.

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Invitrogen and Applied Biosystems to combine

Invitrogen Corporation and Applera Corporation today announced that their Boards of Directors have approved a definitive merger agreement, under which Invitrogen will acquire all of the outstanding shares of Applera's Applied Biosystems Group a cash and stock transaction valued at $6.7 billion.

This strategic combination will create a global leader in biotechnology reagents and systems generating approximately $3.5 billion in combined sales, with significant commercial, operational and technical scale, uniquely positioned to accelerate and drive new discoveries and commercial applications. The combined company will have a major presence in key growth markets and exceptional technical capabilities in the areas of genetic analysis, proteomics, cell biology and cell systems. Following the close of the transaction, the combined organization will be named Applied Biosystems, Inc. and will have its corporate headquarters in Carlsbad, California.

Under the terms of the merger agreement, Applera-Applied Biosystems shareholders will receive $38.00 for each share of Applera-Applied Biosystems stock they own in the form of Invitrogen common stock and cash. The expected split between cash and stock is 45% and 55%, respectively. Applera-Applied Biosystems shareholders will receive a value of $38.00 a share if the 20 day volume-weighted average price of Invitrogen common stock is in the range of $43.69 - $46.00 three business days prior to the close of the transaction. The total value per share will differ if Invitrogen's 20 day volume-weighted average price is above or below that range, measured shortly prior to the close of the transaction. The consideration represents a premium of 17% to Applied Biosystems's closing price on June 11, 2008, or 12% to Applied Biosystems's average closing price in the last 30 trading days. Applera-Applied Biosystems shareholders also will have the option to request all cash or all stock, subject to possible proration. Upon completion of the transaction, Invitrogen shareholders will own the majority of the company.

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EBI-Led Consortium to Study How to Turn EU Bio-Databases Into Bioinformatic Network

The European Commission has awarded €4.5 million ($7 million) to a consortium of 32 research organizations, universities, and companies from 13 countries to determine how to transform Europe’s biomedical data resources into a transnational “sustainable integrative bioinformatics network” for the life sciences.

The consortium is led by the European Bioinformatics Institute. The first year and a half of this project, called ELIXIR, for European Life-science Infrastructure for Biological Information, is aimed at gathering input, performing technical-feasibility studies, and doing user surveys among researchers who generate and use data, and develop tools.

Much like the Oxford English Dictionary, which will remain useful as long as people speak English, so, too, will “the infrastructure for biological information … continue as long as people are interested in biology, health, and medicine,” she said.

But provisions must be made to allow that to happen, including upgrading the infrastructure itself, promoting database interoperability, and using distributed annotation technologies.

ELIXIR will not unfold with “a big bang” but rather evolve in stages. And it does not solely concern the lions of the European database world such as EBI and the Swiss Institute of Bioinformatics, said Thornton. There are internationally collaboratively maintained databases such as InterPro and IntAct, and also many small ones.

According to Thornton, of the world’s approximately 900 biomedical databases, 40 percent are in Europe, many of which are specialist databases. “They are often in an individual’s laboratory; a research group may have developed a data resource that other people begin to use, and we really need to find a way to incorporate those data resources into the larger network in a way that people can access them easily and without necessarily knowing that they were there in the first place,” she said.

ELIXIR will help link the core and the specialist resources more closely while remaining as “seamless and transparent as possible to our users,” said Thornton. Clicking through databases from link to link is possible for researchers, she said, but clickthrough gymnastics becomes an impossible exercise when a microarray delivers a list of hundreds of genes that must be analyzed with a systems perspective, requiring data to be plowed and mined that is stored in different ways with differing vocabularies.

Interactive WikiProteins Project Invites Researchers to Annotate Biological Concepts

Hoping to bring together “a million minds” to annotate proteins, a team of researchers has launched a large-scale, community-based project called WikiProteins that combines automated text, data, and concept mining, manual annotation, and a newly developed software component called the Knowlet.

The project, which aims to annotate proteins and protein-related biomedical concepts such as diseases or organisms, will be powered by a platform technology designed by a group of scientists and a Rockville, Md.-based startup and will be made available free of charge in perpetuity for the scientific community and the public.

Called WikiProfessional, the platform “in a technical sense powers the community-version that we have now put out there, but you could take exactly the same technology platform and install it locally at a pharmaceutical company for them to do drug-lead discovery,” said Albert Mons, a computational linguist and co-founder of the startup, Knewco.

“Philosophically we wanted to hand off the responsibility for the quality of the content of the system to the community and then provide generic technology that can be used to grow the knowledgebase on a daily basis,”

Given high-throughput data and the increasing number of papers describing them, “comprehensive and timely annotation of the literature for facts by any central team of experts [is] an unachievable goal. Computer assistance in the annotation process is, therefore urgently needed,” the scientists wrote in a paper published in the current issue of Genome Biology.

WikiProteins was created over the last two years and announced on May 28, by a team of scientists from the Swiss Institute of Bioinformatics, the GO consortium and the IntAct database at the European Molecular Biology Laboratory-European Bioinformatics Institute, Erasmus Medical Centre, Leiden University Medical Centre, both in the Netherlands, the Brazilian Stela Institute, the WikiMedia Foundation, and Knewco.

The project is an interactive and semantically supported workspace based on Wiki pages and contains a knowledgebase, a navigation tool, and a section on the people in its annotating community. Beneath that layer is a relational Wiki based on WikiData software, an indexer, and software that creates components called Knowlets, which stores the relationships between all the mined concepts.

Knowlets are at the core of this platform, a proprietary concept mining software component and ontology format that Knewco has developed over the last two years.

Writing in the Genome Biology paper, the team said information is mined from scientific publications and the Knowlet links two given concepts, but records that information only once.

“This approach results in a minimal growth of the ‘concept space’ as compared to the text space,” the authors wrote. New and unique facts in the scientific literature expand the corpus to a much lesser degree than the totality of the text generated by new academic journal articles.

Concept pairs are placed in what the WikiProteins creators call a “related concept cloud.” By applying a meta-analysis algorithm, the software calculates a semantic association to reflect the strength and type of relationship the concepts have.

The relationship is dynamic and recalculated based on newly mined information. Its calculated value is based on three factors: factual statements found in the scientific literature or databases, increasing co-occurrence of two concepts in a sentence or a paragraph, and predictive associations based on the overlap of the two concepts.

The WikiProteins terminology has been mapped to concept identifiers in the Wiki-based terminology system called OmegaWiki. WikiProteins and OmegaWiki are driven by a relational database that is linked to the Knowlets by on-the-fly indexing of all Wiki pages. An indexer called Peregrine is designed to recognize concepts by the Wiki, and the indexer is coupled to a terminology system derived from OmegaWiki.

Each biomedical concept has its own page that includes up-to-date annotations. Registered users can become annotators and edit records. WikiProteins shows the new record alongside the original one that was mined from the authoritative databases. Professional annotators at their respective databases can choose to incorporate some of new community-entered information into their database.

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CAS Scientists Help To Explain Diversity of Molecular Structures

By studying the variety of chemical substances and their structures recorded in the CAS REGISTRY^SM database, Chemical Abstracts Service (CAS) scientists have discovered that a limited number of molecular shapes are the frameworks for a disproportionately large percentage of reported substances.

As shown in the CAS study, half of the known organic chemical substances can be described by just 143 shapes.

The analysis, published in The Journal of Organic Chemistry, explains why certain molecular frameworks are more likely to be used in new compounds and may also help identify new regions of chemistry space ripe for exploration.

A blogger studies GSK's pending layoffs and the politics behind them

GSK: Money-Green Outside, Pink-Slip Inside

GSK is indeed wielding the ax today and tomorrow. I'm hearing that that the smallest cuts are around 40% of the entire research staff at the various sites. This is big, and it's bad. . . says Derek

GlaxoSmithKline has been going through some sort of mid-life crisis recently. Their chairman, Jean-Pierre Garnier, just retired amidst the mutter of angry shareholders, for one thing. And the company has been splashing out on some very flashy acquisitions, such as the Sirtris deal which has just now completed. This is all going on against the backdrop of the Avandia disaster, and a perceived drought of current clinical successes.

Now the company is cutting their own head count in research, to what sounds like a pretty serious degree. There have been substantial cuts at their sites in Italy and the UK, and the Research Triangle and Pennsylvania sites are getting it even harder, from what I'm hearing. Some chemistry areas are losing more than half their people. I believe that today is the day that a lot of people are hearing whether they stay or go, and I feel bad just hearing it from a distance, having seen that stuff close up a few times myself.

The proximate cause of all this turmoil is probably the loss of all that Avandia revenue, although that may have just advanced the timetable on some decisions that the eompany was going to make eventually no matter what. Many GSK scientists are (understandably) feeling as if they’re being ditched in favor of a bunch of people whose main advantage is that upper management isn’t so familiar with them yet.

Whether that’s true or not, it’s a tough one to refute. There is a persistent “grass is greener” mentality in the drug industry. Perhaps that’s partly because, on an individual basis, the grass really is often greener. The best way to work your way up in the industry, for the majority of scientists, is to jump ship once in a while, which keeps you from being pigeonholed or taken for granted in your current company. (A less charitable view, accurate in a few cases, is that it’s in some people’s best interest to leave before everyone else catches on to them).

And on a company-wide level, it’s hard not to think of everyone else as being at least a little more competent than your own shop is. That’s because you see the inevitable bozo mistakes of your own workplace up close, whereas you don’t get such good seats for the ones happening elsewhere. And the side that all drug companies show to their competition is a bristling pile of patents and confident press releases about their mighty drug pipelines. You know, looking at your own company’s public face, how much of it is real and how much is bravado or wishful thinking. But it’s hard to keep in mind that the same goes for everyone else, too.

I don’t know how much this effect is contributing to what’s going on at GSK. After all, some of the deals that the company’s making are for specific development compounds that they didn’t have in house. But I’m pretty sure that there are researchers over there who are thinking about whether they could have gotten a sirtuin program off the ground a few years ago, like the one they just bought. Or what would have happened to them if they'd tried. . .

Automatic content for the people

Anyone who has ever built a website knows that maintaining it is a lot of work. There’s just making sure it hasn’t gone offline because the httpd daemon died. Constant monitoring for script kiddies and their SQL injections. Not to mention continually feeding it with fresh content, lest your audience become bored and desert.

I’ve always thought it would be cool to build a site that could more or less look after itself. There’s a myriad of content management systems to choose from, most of which are somewhat hackable in whatever language they happen to be coded in. One of the more mature in this respect is Drupal - which is the engine behind Eureka! Science News. It’s a fully-automated science news portal, using a bunch of customised Drupal modules to aggregate, cluster, categorise and rank articles.

First impressions are excellent. Coders will enjoy this post at Drupal explaining how it all works.

Fresh hurdle for stem cell hunt

Previously blogging on the topic of regenerative medicine in Regenerative Medicine Start-Up Created out of ORNL. A Nobel Prize-winning scientist says it could be tougher than first thought to harness the healing power of stem cells in medicine.

It had been hoped a single "master" cell could potentially be used to repair all damage in a single organ. Stem cells may be more varied than previously thought. Professor Mario Capecchi, from the University of Utah, found surprising clues that different stem cells might be working together in the same organ. This means experimental treatments relying on the wrong type might fail.

Professor Capecchi, writing in the Nature Genetics, said the finding suggested stem cell biology could be "more complicated" than previously thought, which could be bad news for patients hoping for the swift arrival of new therapies.

Bmi1 plays an essential part in the self-renewal of hematopoietic and neural stem cells. To investigate its role in other adult stem cell populations, we generated a mouse expressing a tamoxifen-inducible Cre from the Bmi1 locus. We found that Bmi1 is expressed in discrete cells located near the bottom of crypts in the small intestine, predominantly four cells above the base of the crypt (+4 position). Over time, these cells proliferate, expand, self-renew and give rise to all the differentiated cell lineages of the small intestine epithelium. The induction of a stable form of -catenin in these cells was sufficient to rapidly generate adenomas. Moreover, ablation of Bmi1⁺ cells using a Rosa26 conditional allele, expressing diphtheria toxin, led to crypt loss. These experiments identify Bmi1 as an intestinal stem cell marker in vivo. Unexpectedly, the distribution of Bmi1-expressing stem cells along the length of the small intestine suggested that mammals use more than one molecularly distinguishable adult stem cell subpopulation to maintain organ homeostasis.

Do you want to know more? Nature Genetics Published online: 8 June 2008

How Sequencing Is Done

At JGI, we use whole-genome shotgun sequencing. This is a technique for determining the DNA sequence of a genome by randomly shearing the DNA, sequencing multiple fragments whose sequences overlap, and inferring the original sequence by reassembling the fragments. Three sizes of fragments are sequenced, 2-4 kb (kilobase, or 1000 bases), 8-10 kb, and 40 kb. This explanation follows the procedure for 2-4-kb fragments.

Animation of the JGI production sequencing process

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Roadrunner was possibly only five to 50 times less powerful than the human brain

Fastest supercomputer in the world proves one in a million billion

Roadrunner was always expected to be fast out of the blocks. And after a test run one night in the city of Poughkeepsie, New York, its creators are far from disappointed.

Built from microchips originally destined for games consoles, Roadrunner is the world's latest supercomputer. Yesterday it was officially crowned the fastest computer around, having performed a record million billion calculations per second.

As an indication of how fast this is, manufacturers explained that if 6 billion people were to do one sum a second on calculator, it would take 46 years to do what RoadRunner could do in a day. The world's first supercomputer, the Cray 1 built in the mid-1970s, would take 1,500 years to finish a calculation that Roadrunner would perform in two hours.

For six months, the computer will direct its formidable processing power at scientific problems. It will analyse how HIV vaccines should best be administered, and map the region of the human brain that governs vision.

In another series of tests, it will churn out data on whether firing laser beams into plasmas will trigger nuclear fusion, which advocates believe could one day bring us almost limitless cheap energy. Other projects will focus on testing and improving the accuracy of climate change models.

Alan Dix, professor of computing at Lancaster University, said that by rough calculations, Roadrunner was possibly only five to 50 times less powerful than the human brain. "Wait another three to five years and it will be there," he said.

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GSK collaborates on immune disease research

GlaxoSmithKline has inked a five year, $25 million collaboration deal with the Disease Institute of Boston to conduct on immunoinflammation research. GSK and IDI researchers will develop joint grant proposals in targeted areas of research under an Alliance Research grant program. GSK gets first dibs on any drug targets identified through the collaboration.

"GSK is committed to becoming a world leader within 3 years in drug discovery of immuno-inflammation," said Jose Carlos Gutierrez-Ramos, head of the Immuno-Inflammation Center of Excellence for Drug Discovery of GSK. "This agreement fits perfectly with our strategy to pursue scientific excellence and technologies both internally and externally."

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Unofficial Google Shell

goosh.org - the unofficial google shell (http://goosh.org/).
It is pretty neat and useful in its neonatal state itself, like to read a feed, you can type, for eg:

r http://www.google.com/reader/public/atom/user/11136726768885096694/label/cbn-roll

and gets default 4 latest feeds, or you can check out a ncbi accession by typing, for eg:

NP_001108376

and get to the Fugu fish refseq link.

The most useful thing is the fact that it it text based and quite easy to parse visually as well as via scripts.
Another cool feature for me right now is the shell translation, like to get the english word for the norwegian word 'hvor', all I have to do is type:

t no en hvor

which correctly says:
translating "hvor" from "no" to "en":

"where"

More discussion going on at http://tech.slashdot.org/article.pl?sid=08/06/02/222234&from=rss .
Enjoy!

Regenerative Medicine Start-Up Created out of ORNL

Battelle Ventures has spun out a firm from the U.S. Department of Energy’s Oak Ridge National Laboratory (ORNL), with an initial $1.5 million seed investment. The company, called NellOne Therapeutics, will develop regenerative medicines. The funding will be tranched based on key technical milestones.

Towards a "holy grail" in human medicine: the ability to restore organs damaged through trauma, disease, cancer, or even the normal aging process.

Tissue or organ repair has been the ultimate goal of surgery from ancient times to the present day. Clearly, there is a lot of interest in the regeneration of tissues, and tissue repair in organisms is within reach. However, we are a long way from understanding how to coax the human body into regenerating complex body parts after injury or disease. As an example, regeneration of amputated limbs in amphibians - “epimorphic” regeneration which includes cellular dedifferentiation in the injured tissues of the limb stump and proliferation of these cells to form a distal blastema which undergoes patterning and growth to restore the missing limb structures. Some of the processes that are relatively little known and most of scientists are keen in understanding are:

• Processes involving cell recruitment of progenitor cells to the site of disease or injury and tissue-specific differentiation
• Growth factors and cytokines responsible for activating the body's own native cells to initiate regeneration
• Integration of the regenerated tissue within the surrounding host tissue and true differentiation through pathways involved in embryonic development
• Regulation of expression of a target gene can induce the expression of one or more tissue-inductive factors
• Direct the differentiation of stem or progenitor cells, or remove a factor that inhibits regeneration
• Ability of differentiating cells of muscle and other tissues to lose their ability to revert to the proliferative state and contribute to organ regeneration

Molecular Connections Private Ltd. Bangalore India has come up with its new Knowledgebase of all activating and inhibitory cell surface receptors and their complexes with the ligand(s) determined to date - Receptome:

• Knowledgebase, is a result of manually mining thousands of papers, on functional ligand-receptor pairs with their role & biological significance in developmental biology, as reported in literature till date
• Careful description of cell surface receptors, ligand(s) and molecular pathways integrated into complex networks and their expression patterns (signatures) involved in tissue regeneration
• Completely deciphered pathways of endogenous growth factors and cytokines and their receptors with their regulatory mechanisms involved in tissue regeneration
• Endogenous modulators or regulators of developmental ligand-receptor(s) widely studied in differentiation of stem or progenitor cells or tissue regeneration
• A platform to identify and track stem cells in different culture programmes using expression profiles of markers
• Comprehensive overview of the synergistic and combinatorial effects of receptors in tissue regeneration

Gene that Induces a Magnetic Signature in Cells Found

A team of scientists have found a way to make human cells produce magnetic nanoparticles by introducing a gene from bacteria. The gene MagA was tested in human kidney cells, though the investigators believe that it will probably be most useful in tracking cell movement in transgenic animals via MRI.

“MagA can be thought of as the equivalent of green fluorescent protein but for magnetic resonance imaging,” says Xiaoping Hu, PhD, professor of biomedical engineering at Emory University and the Georgia Institute of Technology. Dr. Hu anticipates that MagA could find similar applications to green fluorescent protein, with the advantage that magnetic fields can penetrate tissues more easily than light.

MagA comes from magnetotactic bacteria, which can sense the Earth's magnetic field. It encodes a protein that transports dissolved iron across cell membranes. When put into animal cells, MagA triggers the accumulation of lumps of iron oxide a few nanometers wide, the researchers explain. MagA appeared to be nontoxic.

Other researchers from Emory University School of Medicine and Yerkes National Primate Research Center contributed to this study. The results are published in the June issue of Magnetic Resonance in Medicine.

Novartis to Buy Protez for $100M

Novartis has decided to acquire Protez Pharmaceuticals for $100 million at close of the agreement. Novartis will pay up to $300 million if certain clinical milestones, regulatory approvals, and commercial targets are achieved. Protez will become a stand-alone subsidiary of Novartis, maintaining its operations in Malvern, PA.

Protez’ only clinical candidate, PZ-601, is an injectable antibiotic in the carbapenems class of agents. Protez commenced a 100-patient Phase II study for PZ-601 in May 2008 in the U.S. to evaluate the safety and efficacy of PZ-601 in patients with complicated skin and skin structure infections, including cellulites, abscesses, infected wounds, and ulcers. The firms believe that this compound has the potential to be used in bacterial infections resistant to other medicines including MRSA.

“This acquisition,” remarks Christopher M. Cashman, Protez president and CEO, “underscores our company’s infectious disease expertise and novel antimicrobial programs. We believe the growing presence of Novartis in the specialty field of hospital infections provides Protez the support required to fully execute its vision, advance its product pipeline, and positively impact human health.”

The good news in our DNA: Defects you can fix with vitamins and minerals

As the cost of sequencing a single human genome drops rapidly, with one company predicting a price of $100 per person in five years, soon the only reason not to look at your "personal genome" will be fear of what bad news lies in your genes.

University of California, Berkeley, scientists, however, have found a welcome reason to delve into your genetic heritage: to find the slight genetic flaws that can be fixed with remedies as simple as vitamin or mineral supplements.

"There are over 600 human enzymes that use vitamins or minerals as cofactors, and this study reports just what we found by studying one of them," Rine said. "What this means is that, even if the odds of an individual having a defect in one gene is low, with 600 genes, we are all likely to have some mutations that limit one or more of our enzymes."

The subtle effects of variation in enzyme activity may well account for conflicting results of some clinical trials, including the confusing data on the effect of vitamin supplements, he noted. In the future, the enzyme profile of research subjects will have to be taken into account in analyzing the outcome of clinical trials.

If one considers not just vitamin-dependent enzymes but all the 30,000 human proteins in the genome, "every individual would harbor approximately 250 deleterious substitutions considering only the low-frequency variants. These numbers suggest that the aggregate incidence of low-frequency variants could have a significant physiological impact," the researchers wrote in their paper.

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Elevated Levels of Metabolites in CSF Play a Role in HIV Patients with CNS Damage

A team of scientists from The Scripps Research Institute found an increased concentration of certain metabolites in the cerebrospinal fluid (CSF) of monkeys with SIV-induced central nervous system (CNS) disease, a model for HIV patients with CNS damage.

The investigators used global metabolomics to assess the levels of metabolites in CSF before and after SIV-induced encephalitis appeared. They found elevated levels in four categories: carnitine, acyl-carnitines, fatty acids, and phospholipids. Consistent with this, the team reports, a protein known to be important in the generation of fatty acids was increased in the brains of monkeys with SIV-induced encephalitis.

The elevation in free fatty acids and lysophospholipids correlated with increased expression of specific phospholipases in the brains of animals with encephalitis, according to the researchers. One of these, phospholipase A2 isoenzyme, is capable of releasing a number of the fatty acids identified. It was expressed in different areas of the brain in conjunction with glial activation, rather than linked to regions of SIV infection and inflammation. The scientists hypothesize that this indicates widespread alterations in infected brains.

The investigators then went on to try to understand whether the metabolic changes were due to SIV infection or were related to neurological involvement and encephalitis. CSF was collected before infection and approximately six months after infection from animals that did not progress to encephalitis. They found no significant changes in metabolite levels in animals that lacked neurological symptoms. This shows, according to The Scripps team, that the metabolic changes observed in late-stage infection are specifically related to SIV-induced encephalitis.

More research is needed to determine the exact role of the higher level of each metabolite, the researchers note. They point out, though, that many of these metabolites are known to induce receptor signaling and thereby might be able to further modulate CNS function.

The findings are published in the June 2 issue of The Journal of Clinical Investigation.

Finding a job in life sciences: Dr. Elaine Johnson talks about the easiest way to a biotech career

A little over ten years ago, Dr. Elaine Johnson obtained funding from the National Science Foundation to start Bio-Link, an Advanced Technology Education center, focused on biotechnology. Since that time, Dr. Johnson has become a national leader in biotech education, enlisting the country's top educators and industry captains to ensure that community college students receive a quality education and the best preparation possible for entering the workforce.

In this radio interview from Tech Nation, Dr. Johnson talks with Dr. Moira Gunn about the easiest way to a biotech career.

A Career in Biotech

Tech Nation

23 minutes, 10.7mb, recorded 2008-05-21

• Play

USDA Releasing Genomic Data from 150 Bird Flu Viruses

The United States Department of Agriculture has released the complete genetic sequences of 150 different avian influenza viruses and will make the information available through the National Institutes of Health’s GenBank.

The USDA said on Friday that the sequencing data is part of the federal government’s Initiative on Avian Influenza, and that this information will be combined with studies that compare the viruses’ ability to infect poultry such as chickens, turkeys, and domestic ducks.

This virus research that generated this data was conducted by the USDA’s Agricultural Research Service’s Southeast Poultry Research Laboratory (SEPRL), by the University of Georgia, the Ohio State University, the University of Delaware, and the University of Alaska-Fairbanks.

"The project's ultimate goal is to sequence 900 avian influenza viruses from the SEPRL repository," David Suarez, a researcher with SEPRL, said in a statement. "These include avian influenza viruses collected from both poultry and wild bird species in the United States and around the world.

"This sequence information, deciphered by our large team, will help researchers better understand virus biology and improve diagnostic tests for avian influenza viruses," Suarez added.

Sequencing services for the project were conducted by the Houston-based company SeqWright.

Thermo Fisher Acquires Indian Analytical Instruments Firm

Thermo Fisher Scientific said after the close of the market on Monday that it has acquired Chemito Technologies, a Mumbai, India-based supplier of analytical instruments for life sciences and environmental monitoring applications.

Thermo Fisher said that Chemito has annual revenues of roughly $10 million and manufactures its own instruments for gas chromatography, atomic absorption, and UV-Vis spectroscopy. The Waltham, Mass.-based firm will integrate Chemito into its Analytical Technologies segment.

“The strong reputation Chemito has developed through its extensive sales network, now complemented by Thermo Fisher’s breadth of scientific and environmental instrumentation, extends the services we can provide to our customers throughout India,” Thermo Fisher President and CEO Marijn Dekkers said in a statement.

The purchase price was not disclosed.

Conserved Domain Database (CDD) has been updated

The CDD [ http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml ] and the its search tool [ http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi ] has been recently updated. Also check out the latest approach for "automatically assigning subcellular locations" to protein from Newberg and Murphy [ http://pubs.acs.org/cgi-bin/abstract.cgi/jprobs/asap/abs/pr7007626.html].