Nature Methods 6, 105 (2009). doi:10.1038/nmeth0109-105

Author: Nathan Blow

Some researchers say an eighty-year-old statistical method can make setting up and analyzing high-throughput screens and large-scale experiments faster and more efficient. So why are more biologists not flocking to use this tool?

Nature Methods 6, 15 (2009). doi:10.1038/nmeth.f.234

Author: Kelly Rae Chi

After a long period of measured development and a recent surge of technical advances driven by physicists, super-resolution fluorescence microscopy emerged in 2008 as a powerful tool for biologists. Kelly Rae Chi reports.

Nature Methods 6, 34 (2009). doi:10.1038/nmeth.f.239

Author: Allison Doerr

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.Quantitative mass spectrometry–based proteomics is now being applied on a large scale to address interesting biological questions.

Nature Methods 6, 35 (2009). doi:10.1038/nmeth.f.240

Author: Allison Doerr

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.New methods addressing the challenges in membrane protein expression, solubilization and crystallization promise to yield many more atomic structures.

Nature Methods 6, 12 (2009). doi:10.1038/nmeth0109-12

Author: Allison Doerr

A device to cool localized areas of the zebra finch brain allows researchers to investigate how the timing of birdsong is controlled.

Nature Methods 6, 8 (2009). doi:10.1038/nmeth0109-8a

Author: Allison Doerr

A new generation of brilliant X-ray laser sources will be coming online within the next few years. Researchers now show that using these lasers to determine the structures of single molecules should be possible.

Nature Methods 6, 8 (2009). doi:10.1038/nmeth0109-8b

Author: Amy Donner

Scientists create a high-throughput platform for proteome-scale assessment of protein stability.

Nature Methods 6, 10 (2009). doi:10.1038/nmeth0109-10

Author: Michael Eisenstein

A new spin on a popular imaging technique allows researchers to accurately visualize tumors deep within the tissues of live mice.

Nature Methods 6, 19 (2009). doi:10.1038/nmeth.f.235

Author: Daniel Evanko

A brief description of the theory and methods behind super-resolution fluorescence imaging.

Nature Methods 6, 34 (2009). doi:10.1038/nmeth.f.238

Author: Daniel Evanko

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.Automated imaging has the power to transform microscopy into a more quantitative technique with new capabilities.

Nature Methods 6, 36 (2009). doi:10.1038/nmeth.f.243

Author: Daniel Evanko

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.The use of light for active cellular control rather than just passive observation continues to make headway.

Nature Methods 6, 37 (2009). doi:10.1038/nmeth0109-37

Authors: Pedro P Medina & Frank J Slack

A new strategy is presented to functionally knock down microRNAs in a mouse.

Nature Methods 6, 33 (2009). doi:10.1038/nmeth.f.237

Author: Nicole Rusk

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.After constructing a synthetic genome, the challenge is to prove its functionality.

Nature Methods 6, 36 (2009). doi:10.1038/nmeth.f.242

Author: Nicole Rusk

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.Although microRNA target predictions are continually improving, high-throughput validation of direct interaction is still needed.

Nature Methods 6, 7 (2009). doi:10.1038/nmeth0109-7

Author: Nicole Rusk

Tagging ribosomes in a cell type–specific way allows the isolation of mRNAs that are being translated in these cells.

Nature Methods 6, 55 (2009). doi:10.1038/nmeth.1283

Authors: Ariel S Schwartz, Jingkai Yu, Kyle R Gardenour, Russell L Finley Jr & Trey Ideker

Nature Methods 6, 47 (2009). doi:10.1038/nmeth.1279

Authors: Nicolas Simonis, Jean-François Rual, Anne-Ruxandra Carvunis, Murat Tasan, Irma Lemmens, Tomoko Hirozane-Kishikawa, Tong Hao, Julie M Sahalie, Kavitha Venkatesan, Fana Gebreab, Sebiha Cevik, Niels Klitgord, Changyu Fan, Pascal Braun, Ning Li, Nono Ayivi-Guedehoussou, Elizabeth Dann, Nicolas Bertin, David Szeto, Amélie Dricot, Muhammed A Yildirim, Chenwei Lin, Anne-Sophie de Smet, Huey-Ling Kao, Christophe Simon, Alex Smolyar, Jin Sook Ahn, Muneesh Tewari, Mike Boxem, Stuart Milstein, Haiyuan Yu, Matija Dreze, Jean Vandenhaute, Kristin C Gunsalus, Michael E Cusick, David E Hill, Jan Tavernier, Frederick P Roth & Marc Vidal

Nature Methods 6, 33 (2009). doi:10.1038/nmeth.f.236

Author: Natalie de Souza

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.Methods to reprogram somatic cells to pluripotency have improved and will improve further; more biological studies of these cells are forthcoming.

Nature Methods 6, 35 (2009). doi:10.1038/nmeth.f.241

Author: Natalie de Souza

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year's picks for Methods to Watch: here is our (subjective) selection for this year.Optical methods to image deep into thick samples make it increasingly possible to watch biological processes in vivo.

Nature Methods 6, 1 (2009). doi:10.1038/nmeth.f.244

With its tremendous potential for understanding cellular biology now poised to become a reality, super-resolution fluorescence microscopy is our choice for Method of the Year.

Nature Methods 6, 2 (2009). doi:10.1038/nmeth0109-2

The maturation of large-scale protein-protein interaction methodologies calls for improved methods to assess performance and data quality.

Nature Methods 6, 21 (2009). doi:10.1038/nmeth.f.233

Authors: Jennifer Lippincott-Schwartz & Suliana Manley

Super-resolution microscopy is poised to revolutionize our understanding of the workings of the cell. But the technology still has some limitations, and these must be taken into consideration if widespread application is to yield biological insight.

Nature Methods 6, 91 (2009). doi:10.1038/nmeth.1281

Authors: Pascal Braun, Murat Tasan, Matija Dreze, Miriam Barrios-Rodiles, Irma Lemmens, Haiyuan Yu, Julie M Sahalie, Ryan R Murray, Luba Roncari, Anne-Sophie de Smet, Kavitha Venkatesan, Jean-François Rual, Jean Vandenhaute, Michael E Cusick, Tony Pawson, David E Hill, Jan Tavernier, Jeffrey L Wrana, Frederick P Roth & Marc Vidal

Nature Methods 6, 99 (2009). doi:10.1038/nmeth.1276

Authors: Derek Y Chiang, Gad Getz, David B Jaffe, Michael J T O'Kelly, Xiaojun Zhao, Scott L Carter, Carsten Russ, Chad Nusbaum, Matthew Meyerson & Eric S Lander

Nature Methods 6, 83 (2009). doi:10.1038/nmeth.1280

Authors: Kavitha Venkatesan, Jean-François Rual, Alexei Vazquez, Ulrich Stelzl, Irma Lemmens, Tomoko Hirozane-Kishikawa, Tong Hao, Martina Zenkner, Xiaofeng Xin, Kwang-Il Goh, Muhammed A Yildirim, Nicolas Simonis, Kathrin Heinzmann, Fana Gebreab, Julie M Sahalie, Sebiha Cevik, Christophe Simon, Anne-Sophie de Smet, Elizabeth Dann, Alex Smolyar, Arunachalam Vinayagam, Haiyuan Yu, David Szeto, Heather Borick, Amélie Dricot, Niels Klitgord, Ryan R Murray, Chenwei Lin, Maciej Lalowski, Jan Timm, Kirstin Rau, Charles Boone, Pascal Braun, Michael E Cusick, Frederick P Roth, David E Hill, Jan Tavernier, Erich E Wanker, Albert-László Barabási & Marc Vidal

Nature Methods 6, 63 (2009). doi:10.1038/nmeth.1277

Authors: Bernhard Gentner, Giulia Schira, Alice Giustacchini, Mario Amendola, Brian D Brown, Maurilio Ponzoni & Luigi Naldini

Studying microRNA function in vivo requires genetic strategies to generate loss-of-function phenotypes. We used lentiviral vectors to stably and specifically knock down microRNA by overexpressing microRNA target sequences from polymerase II promoters. These vectors effectively inhibited regulation of reporter constructs and natural microRNA targets. We used bone marrow reconstitution with hematopoietic stem cells stably overexpressing miR-223 target sequence to phenocopy the genetic miR-223 knockout mouse, indicating robust interference of microRNA function in vivo.

Nature Methods 6, 71 (2009). doi:10.1038/nmeth.1289

Authors: Doron Gerber, Sebastian J Maerkl & Stephen R Quake

We developed an in vitro protein expression and interaction analysis platform based on a highly parallel and sensitive microfluidic affinity assay, and used it for 14,792 on-chip experiments, which exhaustively measured the protein-protein interactions of 43 Streptococcus pneumoniae proteins in quadruplicate. The resulting network of 157 interactions was denser than expected based on known networks. Analysis of the network revealed previously undescribed physical interactions among members of some biochemical pathways.

Nature Methods 6, 79 (2009). doi:10.1038/nmeth.1278

Authors: Yasuhiro Kamei, Motoshi Suzuki, Kenjiro Watanabe, Kazuhiro Fujimori, Takashi Kawasaki, Tomonori Deguchi, Yoshihiro Yoneda, Takeshi Todo, Shin Takagi, Takashi Funatsu & Shunsuke Yuba

We developed infrared laser–evoked gene operator (IR-LEGO), a microscope system optimized for heating cells without photochemical damage. Infrared irradiation causes reproducible temperature shifts of the in vitro microenvironment in a power-dependent manner. When applied to living Caenorhabditis elegans, IR-LEGO induced heat shock–mediated expression of transgenes in targeted single cells in a more efficient and less deleterious manner than a 440-nm dye laser and elicited physiologically relevant phenotypic responses.

Nature Methods 6, 67 (2009). doi:10.1038/nmeth.1286

Authors: Chad Nusbaum, Toshiro K Ohsumi, James Gomez, John Aquadro, Thomas C Victor, Robert M Warren, Deborah T Hung, Bruce W Birren, Eric S Lander & David B Jaffe

Our variant ascertainment algorithm, VAAL, uses massively parallel DNA sequence data to identify differences between bacterial genomes with high sensitivity and specificity. VAAL detected ∼98% of differences (including large insertion-deletions) between pairs of strains from three species while calling no false positives. VAAL also pinpointed a single mutation between Vibrio cholerae genomes, identifying an antibiotic's site of action by identifying sequence differences between drug-sensitive strains and drug-resistant derivatives.

Nature Methods 6, 75 (2009). doi:10.1038/nmeth.1282

Authors: Jianmin Wu, Tea Vallenius, Kristian Ovaska, Jukka Westermarck, Tomi P Mäkelä & Sampsa Hautaniemi

There is an increasing demand for network analysis of protein-protein interactions (PPIs). We introduce a web-based protein interaction network analysis platform (PINA), which integrates PPI data from six databases and provides network construction, filtering, analysis and visualization tools. We demonstrated the advantages of PINA by analyzing two human PPI networks; our results suggested a link between LKB1 and TGFβ signaling, and revealed possible competitive interactors of p53 and c-Jun.