Nature Biotechnology

People.

Publication Date: 2008 May PMID: 18464789
Authors:
Journal: Nat Biotechnol

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Identifying a robust pool of leadership candidates.

Publication Date: 2008 May PMID: 18464788
Authors: Rychlik, B.
Journal: Nat Biotechnol

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The minimum information about a genome sequence (MIGS) specification.

Publication Date: 2008 May PMID: 18464787
Authors: Field, D. - Garrity, G. - Gray, T. - Morrison, N. - Selengut, J. - Sterk, P. - Tatusova, T. - Thomson, N. - Allen, M. J. - Angiuoli, S. V. - Ashburner, M. - Axelrod, N. - Baldauf, S. - Ballard, S. - Boore, J. - Cochrane, G. - Cole, J. - Dawyndt, P. - De Vos, P. - DePamphilis, C. - Edwards, R. - Faruque, N. - Feldman, R. - Gilbert, J. - Gilna, P. - Glockner, F. O. - Goldstein, P. - Guralnick, R. - Haft, D. - Hancock, D. - Hermjakob, H. - Hertz-Fowler, C. - Hugenholtz, P. - Joint, I. - Kagan, L. - Kane, M. - Kennedy, J. - Kowalchuk, G. - Kottmann, R. - Kolker, E. - Kravitz, S. - Kyrpides, N. - Leebens-Mack, J. - Lewis, S. E. - Li, K. - Lister, A. L. - Lord, P. - Maltsev, N. - Markowitz, V. - Martiny, J. - Methe, B. - Mizrachi, I. - Moxon, R. - Nelson, K. - Parkhill, J. - Proctor, L. - White, O. - Sansone, S. A. - Spiers, A. - Stevens, R. - Swift, P. - Taylor, C. - Tateno, Y. - Tett, A. - Turner, S. - Ussery, D. - Vaughan, B. - Ward, N. - Whetzel, T. - San Gil, I. - Wilson, G. - Wipat, A.
Journal: Nat Biotechnol

With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.

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A modular approach for integrative analysis of large-scale gene-expression and drug-response data.

Publication Date: 2008 May PMID: 18464786
Authors: Kutalik, Z. - Beckmann, J. S. - Bergmann, S.
Journal: Nat Biotechnol

High-throughput technologies are now used to generate more than one type of data from the same biological samples. To properly integrate such data, we propose using co-modules, which describe coherent patterns across paired data sets, and conceive several modular methods for their identification. We first test these methods using in silico data, demonstrating that the integrative scheme of our Ping-Pong Algorithm uncovers drug-gene associations more accurately when considering noisy or complex data. Second, we provide an extensive comparative study using the gene-expression and drug-response data from the NCI-60 cell lines. Using information from the DrugBank and the Connectivity Map databases we show that the Ping-Pong Algorithm predicts drug-gene associations significantly better than other methods. Co-modules provide insights into possible mechanisms of action for a wide range of drugs and suggest new targets for therapy.

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Research highlights.

Publication Date: 2008 May PMID: 18464785
Authors:
Journal: Nat Biotechnol

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Retinal anti-angiogenesis by a new route.

Publication Date: 2008 May PMID: 18464784
Authors: Bicknell, R.
Journal: Nat Biotechnol

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Customized signaling with reconfigurable protein scaffolds.

Publication Date: 2008 May PMID: 18464783
Authors: Guye, P. - Weiss, R.
Journal: Nat Biotechnol

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Flavivirus DNA vaccine with a kick.

Publication Date: 2008 May PMID: 18464782
Authors: Barrett, A. D.
Journal: Nat Biotechnol

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Recent patent applications in drug screening.

Publication Date: 2008 May PMID: 18464781
Authors:
Journal: Nat Biotechnol

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Designing around patents: a guideline.

Publication Date: 2008 May PMID: 18464780
Authors: Wang, S. J.
Journal: Nat Biotechnol

An analysis of US Federal Circuit decisions shows strategies for designing around patents.

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Is personalized medicine finally arriving?

Publication Date: 2008 May PMID: 18464779
Authors: Allison, M.
Journal: Nat Biotechnol

It's no gold rush, but dozens of players are emerging in personalized medicine, with biotechs, big and small, leading the way. Some big pharma companies and even payers remain skeptical, but economics aside, the real winners will be patients.

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The impact of greed on academic medicine and patient care.

Publication Date: 2008 May PMID: 18464778
Authors: Frangioni, J. V.
Journal: Nat Biotechnol

To what extent is the increasing emphasis on profit generation at US academic institutions shackling intellectual freedom and compromising healthcare?

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Off the rails or on the mark?

Publication Date: 2008 May PMID: 18464777
Authors: Chataway, J. - Tait, J. - Wield, D.
Journal: Nat Biotechnol

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Off the rails or on the mark?

Publication Date: 2008 May PMID: 18464776
Authors: Heinemann, J. A.
Journal: Nat Biotechnol

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Legal issues for biological research standards.

Publication Date: 2008 May PMID: 18464775
Authors: Contreras, J. L.
Journal: Nat Biotechnol

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Response to Demonizing phytate.

Publication Date: 2008 May PMID: 18464774
Authors:
Journal: Nat Biotechnol

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Response to HIV vaccine trials in India.

Publication Date: 2008 May PMID: 18464773
Authors:
Journal: Nat Biotechnol

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Demonizing phytate.

Publication Date: 2008 May PMID: 18464772
Authors: Shamsuddin, A. M.
Journal: Nat Biotechnol

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HIV vaccine trials in India.

Publication Date: 2008 May PMID: 18464771
Authors: Berkley, S.
Journal: Nat Biotechnol

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The special treatment.

Publication Date: 2008 May PMID: 18464770
Authors: Osborne, R.
Journal: Nat Biotechnol

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Biotech slumps in Q1.

Publication Date: 2008 May PMID: 18464769
Authors: Lawrence, S.
Journal: Nat Biotechnol

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M&A not the only solution.

Publication Date: 2008 May PMID: 18464768
Authors: Huggett, B.
Journal: Nat Biotechnol

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IL-1 trap go-ahead.

Publication Date: 2008 May PMID: 18464767
Authors: Ratner, M.
Journal: Nat Biotechnol

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Dynavax trial halted.

Publication Date: 2008 May PMID: 18464766
Authors: DeFrancesco, L.
Journal: Nat Biotechnol

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No way out for small public firms?

Publication Date: 2008 May PMID: 18464765
Authors: Mitchell, P.
Journal: Nat Biotechnol

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Bush pushes plant energy.

Publication Date: 2008 May PMID: 18464764
Authors: Fox, J. L.
Journal: Nat Biotechnol

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Changes for ESAs.

Publication Date: 2008 May PMID: 18464763
Authors: Spalding, B. J.
Journal: Nat Biotechnol

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New Alzheimer's endpoints?

Publication Date: 2008 May PMID: 18464762
Authors: Aldridge, S.
Journal: Nat Biotechnol

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GM grass trials blocked.

Publication Date: 2008 May PMID: 18464761
Authors: Fox, J. L.
Journal: Nat Biotechnol

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Patent threat in emerging economies shifts to biotech.

Publication Date: 2008 May PMID: 18464760
Authors: Jayaranam, K.
Journal: Nat Biotechnol

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Courts deny Pfizer access.

Publication Date: 2008 May PMID: 18464759
Authors: Gura, T.
Journal: Nat Biotechnol

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Inhaled insulin's last gasp?

Publication Date: 2008 May PMID: 18464758
Authors: Kling, J.
Journal: Nat Biotechnol

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EU to monitor for Chinese GM rice.

Publication Date: 2008 May PMID: 18464757
Authors: Huggett, B.
Journal: Nat Biotechnol

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Regulators scramble to tighten loopholes after heparin debacle.

Publication Date: 2008 May PMID: 18464756
Authors: Jia, H.
Journal: Nat Biotechnol

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Nothing to see here.

Publication Date: 2008 May PMID: 18464755
Authors:
Journal: Nat Biotechnol

Based on one company's past poor publishing practices, a top-tier medical journal misguidedly stigmatizes any paper from industry.

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Looking forward, looking back.

Publication Date: 2008 May PMID: 18464754
Authors:
Journal: Nat Biotechnol

Amgen's retrospective sortie into personalized Vectibix treatment poses some difficult questions for regulators concerning the oversight of companion diagnostics.

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Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina).

Publication Date: 2008 May PMID: 18454138
Authors: Martinez, D. - Berka, R. M. - Henrissat, B. - Saloheimo, M. - Arvas, M. - Baker, S. E. - Chapman, J. - Chertkov, O. - Coutinho, P. M. - Cullen, D. - Danchin, E. G. - Grigoriev, I. V. - Harris, P. - Jackson, M. - Kubicek, C. P. - Han, C. S. - Ho, I. - Larrondo, L. F. - de Leon, A. L. - Magnuson, J. K. - Merino, S. - Misra, M. - Nelson, B. - Putnam, N. - Robbertse, B. - Salamov, A. A. - Schmoll, M. - Terry, A. - Thayer, N. - Westerholm-Parvinen, A. - Schoch, C. L. - Yao, J. - Barbote, R. - Nelson, M. A. - Detter, C. - Bruce, D. - Kuske, C. R. - Xie, G. - Richardson, P. - Rokhsar, D. S. - Lucas, S. M. - Rubin, E. M. - Dunn-Coleman, N. - Ward, M. - Brettin, T. S.
Journal: Nat Biotechnol

Trichoderma reesei is the main industrial source of cellulases and hemicellulases used to depolymerize biomass to simple sugars that are converted to chemical intermediates and biofuels, such as ethanol. We assembled 89 scaffolds (sets of ordered and oriented contigs) to generate 34 Mbp of nearly contiguous T. reesei genome sequence comprising 9,129 predicted gene models. Unexpectedly, considering the industrial utility and effectiveness of the carbohydrate-active enzymes of T. reesei, its genome encodes fewer cellulases and hemicellulases than any other sequenced fungus able to hydrolyze plant cell wall polysaccharides. Many T. reesei genes encoding carbohydrate-active enzymes are distributed nonrandomly in clusters that lie between regions of synteny with other Sordariomycetes. Numerous genes encoding biosynthetic pathways for secondary metabolites may promote survival of T. reesei in its competitive soil habitat, but genome analysis provided little mechanistic insight into its extraordinary capacity for protein secretion. Our analysis, coupled with the genome sequence data, provides a roadmap for constructing enhanced T. reesei strains for industrial applications such as biofuel production.

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CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.

Publication Date: 2008 May PMID: 18438402
Authors: Hyde, S. C. - Pringle, I. A. - Abdullah, S. - Lawton, A. E. - Davies, L. A. - Varathalingam, A. - Nunez-Alonso, G. - Green, A. M. - Bazzani, R. P. - Sumner-Jones, S. G. - Chan, M. - Li, H. - Yew, N. S. - Cheng, S. H. - Christopher Boyd, A. - Davies, J. C. - Griesenbach, U. - Porteous, D. J. - Sheppard, D. N. - Munkonge, F. M. - Alton, E. W. - Gill, D. R.
Journal: Nat Biotechnol

Pulmonary delivery of plasmid DNA (pDNA)/cationic liposome complexes is associated with an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response and brief duration of transgene expression. We demonstrate that retention of even a single CpG in pDNA is sufficient to elicit an inflammatory response, whereas CpG-free pDNA vectors do not. Using a CpG-free pDNA expression vector, we achieved sustained (>or=56 d) in vivo transgene expression in the absence of lung inflammation.

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A combinatorial library of lipid-like materials for delivery of RNAi therapeutics.

Publication Date: 2008 May PMID: 18438401
Authors: Akinc, A. - Zumbuehl, A. - Goldberg, M. - Leshchiner, E. S. - Busini, V. - Hossain, N. - Bacallado, S. A. - Nguyen, D. N. - Fuller, J. - Alvarez, R. - Borodovsky, A. - Borland, T. - Constien, R. - de Fougerolles, A. - Dorkin, J. R. - Narayanannair Jayaprakash, K. - Jayaraman, M. - John, M. - Koteliansky, V. - Manoharan, M. - Nechev, L. - Qin, J. - Racie, T. - Raitcheva, D. - Rajeev, K. G. - Sah, D. W. - Soutschek, J. - Toudjarska, I. - Vornlocher, H. P. - Zimmermann, T. S. - Langer, R. - Anderson, D. G.
Journal: Nat Biotechnol

The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2'-O-methyl (2'-OMe) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics.

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The impact of target site accessibility on the design of effective siRNAs.

Publication Date: 2008 May PMID: 18438400
Authors: Tafer, H. - Ameres, S. L. - Obernosterer, G. - Gebeshuber, C. A. - Schroeder, R. - Martinez, J. - Hofacker, I. L.
Journal: Nat Biotechnol

Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs.

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Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events.

Publication Date: 2008 Apr 23 PMID: 18437154
Authors: Guerrini, M. - Beccati, D. - Shriver, Z. - Naggi, A. - Viswanathan, K. - Bisio, A. - Capila, I. - Lansing, J. C. - Guglieri, S. - Fraser, B. - Al-Hakim, A. - Gunay, N. S. - Zhang, Z. - Robinson, L. - Buhse, L. - Nasr, M. - Woodcock, J. - Langer, R. - Venkataraman, G. - Linhardt, R. J. - Casu, B. - Torri, G. - Sasisekharan, R.
Journal: Nat Biotechnol

Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta1-->3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here.

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Single-round infectious particles enhance immunogenicity of a DNA vaccine against West Nile virus.

Publication Date: 2008 May PMID: 18425125
Authors: Chang, D. C. - Liu, W. J. - Anraku, I. - Clark, D. C. - Pollitt, C. C. - Suhrbier, A. - Hall, R. A. - Khromykh, A. A.
Journal: Nat Biotechnol

DNA vaccines encoding replication-defective viruses are safer than inactivated or live attenuated viruses but may fail to stimulate an immune response sufficient for effective vaccination. We augment the protective capacity of a capsid-deleted flavivirus DNA vaccine by co-expressing the capsid protein from a separate promoter. In transfected cells, the capsid-deleted RNA transcript is replicated and translated to produce secreted virus-like particles lacking the nucleocapsid. This RNA is also packaged with the help of co-expressed capsid protein to form secreted single-round infectious particles (SRIPs) that deliver the RNA into neighboring cells. In SRIP-infected cells, the RNA is replicated again and produces additional virus-like particles, but in the absence of capsid RNA no SRIPs are formed and no further spread occurs. Compared with an otherwise identical construct that does not encode capsid, our vaccine offers better protection to mice after lethal West Nile virus infection. It also elicits virus-neutralizing antibodies in horses. This approach may enable vaccination against pathogenic flaviviruses other than West Nile virus.

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