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Editorials

Method of the Year 2009 voting begins p547

doi:10.1038/nmeth0809-547a

We are now accepting nominations and collecting votes for the Method of the Year 2009.


Software by any name pp547 - 548

doi:10.1038/nmeth0809-547b

Computational biologists are often tempted to avoid providing a named software implementation of their new algorithm, but resisting this temptation helps avoid difficulties later on and benefits the wider community of biologists.


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Correspondence

MAQGene: software to facilitate C. elegans mutant genome sequence analysis p549

Henry Bigelow, Maria Doitsidou, Sumeet Sarin & Oliver Hobert

doi:10.1038/nmeth.f.260


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SHOREmap: simultaneous mapping and mutation identification by deep sequencing pp550 - 551

Korbinian Schneeberger, Stephan Ossowski, Christa Lanz, Trine Juul, Annabeth Høgh Petersen, Kåre Lehmann Nielsen, Jan-Elo Jørgensen, Detlef Weigel & Stig Uggerhø Andersen

doi:10.1038/nmeth0809-550


Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling pp551 - 552

Daniel J Mandell, Evangelos A Coutsias & Tanja Kortemme

doi:10.1038/nmeth0809-551


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Research Highlights

Mass spectrometers on a chip p555

Allison Doerr

doi:10.1038/nmeth0809-555

A prototype for a mass spectrometer with single-molecule sensitivity has prospects for single-cell proteomics.


Actions speak louder pp556 - 557

Michael Eisenstein

doi:10.1038/nmeth0809-556a

A fluorescence resonance energy transfer (FRET)-based biosensor helps scientists monitor the activation of an essential signaling protein over the course of embryogenesis in Drosophila melanogaster.


New shapes of prions pp556 - 557

Irene Kaganman

doi:10.1038/nmeth0809-556b

Modification of a system for rapid amplification of misfolded prion proteins allows de novo generation of these infectious molecules and provides a glimpse of the diverse range of possible misfolded prion strains.


News in brief p557

doi:10.1038/nmeth0809-557


Network countdown p558

Nicole Rusk

doi:10.1038/nmeth0809-558

Researchers lay the foundation for networks that will self-destruct after being exposed to a predetermined number of stimuli.


Clinical proteomics on target p560

Allison Doerr

doi:10.1038/nmeth0809-560

A multilaboratory study designed to assess the reproducibility of multiple reaction monitoring (MRM) mass spectrometry–based proteomics demonstrates the promise of this technology for disease biomarker verification.


A good nose for stem cells p562

Natalie de Souza

doi:10.1038/nmeth0809-562

Cells can be delivered to the rodent brain noninvasively, via the nasal cavity.


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News and Views

Probing the basis for genotype-phenotype relationships pp565 - 566

Byung-Kwan Cho & Bernhard Ø Palsson

doi:10.1038/nmeth0809-565

Transposon mutagenesis coupled with microarray analysis helps to rapidly generate information about changing genotype-phenotype relationships in laboratory-evolved bacteria.

See also: Brief Communication by Goodarzi et al.


New genetic tools for cell lineage analysis in Drosophila pp566 - 568

Tzumin Lee

doi:10.1038/nmeth0809-566

Real-time lineage tracing in flies gets a boost with three techniques to specifically label a progenitor's daughter cells.

See also: Brief Communication by Griffin et al. | Brief Communication by Evans et al.


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Review

Statistical methods for analysis of high-throughput RNA interference screens pp569 - 575

Amanda Birmingham, Laura M Selfors, Thorsten Forster, David Wrobel, Caleb J Kennedy, Emma Shanks, Javier Santoyo-Lopez, Dara J Dunican, Aideen Long, Dermot Kelleher, Queta Smith, Roderick L Beijersbergen, Peter Ghazal & Caroline E Shamu

doi:10.1038/nmeth.1351


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Brief Communications

Conditional and reversible disruption of essential herpesvirus proteins pp577 - 579

Mandy Glas zlig, Andreas Busche, Karen Wagner, Martin Messerle & Eva Maria Borst

doi:10.1038/nmeth.1346

A system for inducible protein degradation, originally developed for mammalian cells, is applied to essential viral proteins and will allow functional studies in a wide range of viruses.


Global discovery of adaptive mutations pp581 - 583

Hani Goodarzi, Alison K Hottes & Saeed Tavazoie

doi:10.1038/nmeth.1352

This array-based discovery tool creates linkage between functional mutations and selectable markers across a bacterial genome and can thus distinguish between adaptive and neutral mutations.

See also: News and Views by Cho & Palsson


Mass spectrometry of membrane transporters reveals subunit stoichiometry and interactions pp585 - 587

Nelson P Barrera, Shoshanna C Isaacson, Min Zhou, Vassiliy N Bavro, Alex Welch, Theresia A Schaedler, Markus A Seeger, Ricardo Núñez Miguel, Vladimir M Korkhov, Hendrik W van Veen, Henrietta Venter, Adrian R Walmsley, Christopher G Tate & Carol V Robinson

doi:10.1038/nmeth.1347

A generally applicable approach to analyze intact membrane protein complexes by mass spectrometry is reported. This method allows subunit stoichiometry, lipid binding and the effects of post-translational modifications on complex formation to be explored.


Metabolic network analysis integrated with transcript verification for sequenced genomes pp589 - 592

Ani Manichaikul, Lila Ghamsari, Erik F Y Hom, Chenwei Lin, Ryan R Murray, Roger L Chang, S Balaji, Tong Hao, Yun Shen, Arvind K Chavali, Ines Thiele, Xinping Yang, Changyu Fan, Elizabeth Mello, David E Hill, Marc Vidal, Kourosh Salehi-Ashtiani & Jason A Papin

doi:10.1038/nmeth.1348

Iterative cycles of metabolic modeling and experimental open reading frame verification in Chlamydomonas reinhardtii lay the groundwork for more accurate gene annotation and provide resources for metabolic engineering.


Virtual terminator nucleotides for next-generation DNA sequencing pp593 - 595

Jayson Bowers, Judith Mitchell, Eric Beer, Philip R Buzby, Marie Causey, J William Efcavitch, Mirna Jarosz, Edyta Krzymanska-Olejnik, Li Kung, Doron Lipson, Geoffrey M Lowman, Subramanian Marappan, Peter McInerney, Adam Platt, Atanu Roy, Suhaib M Siddiqi, Kathleen Steinmann & John F Thompson

doi:10.1038/nmeth.1354

Nucleotide analogs modified with a free 3' hydroxyl, maintaining the interactions at the polymerase active site, and a cleavable linker, attaching a fluorescent dye and an inhibitor, are efficient at reading homopolymer runs in a single-molecule sequencing reaction.


Dereplication and de novo sequencing of nonribosomal peptides pp596 - 599

Julio Ng, Nuno Bandeira, Wei-Ting Liu, Majid Ghassemian, Thomas L Simmons, William H Gerwick, Roger Linington, Pieter C Dorrestein & Pavel A Pevzner

doi:10.1038/nmeth.1350

Multistage mass spectrometry and algorithms for spectral alignment and dereplication allow sequencing of nonribosomal peptides, pharmacologically important compounds that are not encoded in the genome but built by nonribosomal peptide synthetases.


The twin spot generator for differential Drosophila lineage analysis pp600 - 602

Ruth Griffin, Anne Sustar, Marianne Bonvin, Richard Binari, Alberto del Valle Rodriguez, Amber M Hohl, Jack R Bateman, Christians Villalta, Elleard Heffern, Didier Grunwald, Chris Bakal, Claude Desplan, Gerold Schubiger, C-ting Wu & Norbert Perrimon

doi:10.1038/nmeth.1349

This technique, adapted from mosaic analysis with double markers in mice, relies on mitotic recombination to reconstitute sequences encoding EGFP or mRFP1. After cell division, each daughter cell contains one fluorescent marker, causing a green and a red twin spot that can be traced through development.

See also: News and Views by Lee


G-TRACE: rapid Gal4-based cell lineage analysis in Drosophila pp603 - 605

Cory J Evans, John M Olson, Kathy T Ngo, Eunha Kim, Noemi E Lee, Edward Kuoy, Alexander N Patananan, Daniel Sitz, PhuongThao Tran, Minh-Tu Do, Kevin Yackle, Albert Cespedes, Volker Hartenstein, Gerald B Call & Utpal Banerjee

doi:10.1038/nmeth.1356

A Gal4-based system in Drosophila reports on gene expression at a given developmental stage combined with lineage information on expression at earlier developmental stages.

See also: News and Views by Lee


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Articles

Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS) pp606 - 612

Greg L Hura, Angeli L Menon, Michal Hammel, Robert P Rambo, Farris L Poole II, Susan E Tsutakawa, Francis E Jenney Jr, Scott Classen, Kenneth A Frankel, Robert C Hopkins, Sung-jae Yang, Joseph W Scott, Bret D Dillard, Michael W W Adams & John A Tainer

doi:10.1038/nmeth.1353

High-throughput analyses of macromolecular shape and oligomeric state at approx15 Å resolution are possible with a partially automated small angle X-ray scattering (SAXS) pipeline. Though X-ray crystallography provides higher-resolution structural information than SAXS, SAXS analysis is faster and has a higher success rate, which may have implications for how structural genomics research is performed.


Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human pp613 - 618

Kun Zhang, Jin Billy Li, Yuan Gao, Dieter Egli, Bin Xie, Jie Deng, Zhe Li, Je-Hyuk Lee, John Aach, Emily M Leproust, Kevin Eggan & George M Church

doi:10.1038/nmeth.1357

Padlock probes, synthesized in large scale on programmable microarrays, capture expressed single-nucleotide polymorphisms for high-throughput sequencing in this method for RNA allelotyping. The approach combines the sensitivity of digital expression measurements with the efficiency of targeted resequencing to quantify allele specific gene expression in various tissues across several individuals.


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Technology Feature

Cell culture: building a better matrix pp619 - 622

Nathan Blow

doi:10.1038/nmeth0809-619

With the realization that cells interact extensively with their surrounding microenvironments during growth and development, the challenge for researchers has become designing three-dimensional culture systems that more closely mimic those relationships.


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