Nature Methods Contents: November 2013 Volume 10 pp 1037 - 1133

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TABLE OF CONTENTS November 2013 Volume 10, Issue 11 In This Issue Editorial This Month Correspondence Research Highlights Commentary Technology Feature News and Views Brief Communications Articles Application Note Advertisement EASYstrainer™ Cell Sieve - For Filtration of Cell Suspensions and Primary Cell Isolates - isn't it EASY?  • Three color-coded mesh sizes • Fits all standard 50 ml tubes • Handle and mantle surface     • for improved aseptic handling • Venting slot for fast filtration • No liquid overspill  • Convenient blister pack Read more: http://www.gbo.com/bioscience Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Reichert Surface Plasmon Resonance (SPR) systems for biomolecular interaction analysis Monitor real-time binding, obtain detailed information for protein interactions with other molecules: kinetics, affinity, thermodynamics and concentration. Easily maintained and affordable, Reichert SPR systems push detection and sensitivity limits for label-free definitive analysis. ReichertSPR.com     Advertisement Accelerate your research with the Gel DocTM EZ System and Image Lab™ software. With the push of a button this award-winning solution gives you publication-ready imaging results in just 10 seconds.    In This Issue Top InThisIssue    Editorial Top Should scientists tell stories?   p1037 doi:10.1038/nmeth.2726 A narrative can effectively communicate scientific information. But when telling a perfect story becomes an end in itself, the scientific process can be easily compromised. This Month Top The author file: Takanari Inoue   p1039 Vivien Marx doi:10.1038/nmeth.2696 Sensors show calcium movement in tiny, cellular antennae. Points of significance: Significance, P values and t-tests   pp1041 - 1042 Martin Krzywinski and Naomi Altman doi:10.1038/nmeth.2698 The P value reported by tests is a probabilistic significance, not a biological one. Correspondence Top Against storytelling of scientific results   p1045 Yarden Katz doi:10.1038/nmeth.2699 See also: Correspondence by Krzywinski & Cairo Reply to: "Against storytelling of scientific results"   p1046 Martin Krzywinski and Alberto Cairo doi:10.1038/nmeth.2700 See also: Correspondence by Katz TCPA: a resource for cancer functional proteomics data OPEN   pp1046 - 1047 Jun Li, Yiling Lu, Rehan Akbani, Zhenlin Ju, Paul L Roebuck et al. doi:10.1038/nmeth.2650 ScientiFig: a tool to build publication-ready scientific figures   p1048 Benoit Aigouy and Vincent Mirouse doi:10.1038/nmeth.2692 Research Highlights Top Roadblocks to reprogramming, cleared The removal or knockdown of an epigenetic repressor, Mbd3, results in near-complete reprogramming of mouse and human somatic cells to pluripotency. Finding function in the folds Single-cell modeling of chromosomal organization could help scientists untangle how genomic organization informs function and vice versa. Modifying chromatin to shut off enhancers Transcription activator-like effectors (TALEs) fused to enzymes that change chromatin signatures interrogate the role of enhancers in gene expression. A well-preserved program Genes that restore pluripotency to mature mouse cells can initiate similar reprogramming in more distantly related species. Designer binders Researchers define rational design principles to make a small-molecule ligand-binding protein from scratch. When rodents run the research An automated training regimen coaches rats to willingly submit themselves to repeated brain imaging. Single-cell epigenetics Measuring DNA methylation at specific sites in single cells sheds light on early embryo development. Methods in Brief CRISPR-Cas9 for reporter insertions in mouse | Faster imaging volumes | Enzyme function discovery | Standardizing RNA-seq across laboratories Tools in Brief Snapshots of polyadenylation | A mutation for every worm gene | A microchemostat array for yeast proteomics | Highly accurate Cre variants Methods JOBS of the week Post-Doctoral Associate in Molecular Biology University of Minnesota - Twin Cities Postdoctoral research associate University of North Carolina - Chapel Hill Post Doctrol Associate - Bioinformatics University of Massachusett Medical School Postdoctoral research associate University of North Carolina - Chapel Hill More Science jobs from Methods EVENT Modern Synthetic Methods in Organofluorine Chemistry 6th March 2014 London, UK More science events from Commentary Top The need for transparency and good practices in the qPCR literature   pp1063 - 1067 Stephen A Bustin, Vladimir Benes, Jeremy Garson, Jan Hellemans, Jim Huggett et al. doi:10.1038/nmeth.2697 Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not. Technology Feature Top Neuroscience waves to the crowd   pp1069 - 1074 Vivien Marx doi:10.1038/nmeth.2695 Researchers scale up how to crowdsource the mapping of neural circuits. These projects entice crowds by tapping into their spirit of play. News and Views Top Making connections: using networks to stratify human tumors   pp1077 - 1078 Benjamin J Raphael doi:10.1038/nmeth.2704 Network-based stratification (NBS) enables the subtyping of tumors on the basis of their mutational profiles, providing new avenues for cancer research and precision oncology. See also: Article by Hofree et al. Brief Communications Top IntOGen-mutations identifies cancer drivers across tumor types OPEN   pp1081 - 1082 Abel Gonzalez-Perez, Christian Perez-Llamas, Jordi Deu-Pons, David Tamborero, Michael P Schroeder et al. doi:10.1038/nmeth.2642 IntOGen-mutations is a discovery tool for cancer researchers to find driver mutations in genes and pathways. eXtasy: variant prioritization by genomic data fusion   pp1083 - 1084 Alejandro Sifrim, Dusan Popovic, Leon-Charles Tranchevent, Amin Ardeshirdavani, Ryo Sakai et al. doi:10.1038/nmeth.2656 By fusing genomic data, the eXtasy tool effectively prioritizes rare human exomic sequence variants as causal disease variants. Inducible control of gene expression with destabilized Cre   pp1085 - 1088 Richard Sando III, Karsten Baumgaertel, Simon Pieraut, Nina Torabi-Rander, Thomas J Wandless et al. doi:10.1038/nmeth.2640 A system to control gene expression based on a destabilized form of Cre recombinase is reported. Drug-induced stabilization of Cre triggers recombination of 'floxed' alleles in the genome and is here used to genetically modify the activity of neural circuits in the mouse brain. Predicting functional gene interactions with the hierarchical interaction score   pp1089 - 1092 Berend Snijder, Prisca Liberali, Mathieu Frechin, Thomas Stoeger and Lucas Pelkmans doi:10.1038/nmeth.2655 This paper introduces and benchmarks a statistic, the hierarchical interaction score, a statistic for measuring functional interactions between genes from large-scale data, and provides accessible methods for calculating this score. Accounting for technical noise in single-cell RNA-seq experiments   pp1093 - 1095 Philip Brennecke, Simon Anders, Jong Kyoung Kim, Aleksandra A Kolodziejczyk, Xiuwei Zhang et al. doi:10.1038/nmeth.2645 A statistical method that uses spike-ins to model the dependence of technical noise on transcript abundance in single-cell RNA-seq experiments allows identification of genes wherein observed variability in read counts can be reliably interpreted as a signal of biological variability as opposed to the effect of technical noise. Smart-seq2 for sensitive full-length transcriptome profiling in single cells   pp1096 - 1098 Simone Picelli, Åsa K Björklund, Omid R Faridani, Sven Sagasser, Gösta Winberg et al. doi:10.1038/nmeth.2639 Smart-seq2 improves yield and length in single cell-derived cDNA libraries and uses off-the-shelf reagents. Exploiting tertiary structure through local folds for crystallographic phasing   pp1099 - 1101 Massimo Sammito, Claudia Millén, Dayte D Rodríguez, Iñaki M de Ilarduya, Kathrin Meindl et al. doi:10.1038/nmeth.2644 An algorithm and software tool, Borges, utilizes nonspecific tertiary-structure fragment information available in the Protein Data Bank to phase protein X-ray diffraction data. Improved low-resolution crystallographic refinement with Phenix and Rosetta   pp1102 - 1104 Frank DiMaio, Nathaniel Echols, Jeffrey J Headd, Thomas C Terwilliger, Paul D Adams et al. doi:10.1038/nmeth.2648 An approach combining the sampling methodology and energy function of Rosetta with the X-ray refinement methodology of Phenix enables improved low-resolution crystallographic refinement. Genetically encoded calcium indicator illuminates calcium dynamics in primary cilia   pp1105 - 1107 Steven Su, Siew Cheng Phua, Robert DeRose, Shuhei Chiba, Keishi Narita et al. doi:10.1038/nmeth.2647 By targeting calcium indicators to primary cilia, micrometer-long protrusions from the cellular plasma membrane, the authors measure Ca2+ signaling in these sensory organelles. Advertisement Patient-derived xenograft resource  The enormous cost, and high failure rate of cancer drug development have highlighted the need for new preclinical strategies and resources. To this end, a library of more diverse and representative patient-derived tumor xenograft models has been created. We utilize NOD scid IL2 receptor gamma chain knockout mice (NSG), constructed by JAX Professor Lenny Shultz, as the mouse host.   Articles Top Network-based stratification of tumor mutations OPEN   pp1108 - 1115 Matan Hofree, John P Shen, Hannah Carter, Andrew Gross and Trey Ideker doi:10.1038/nmeth.2651 This paper reports a strategy for combining somatic mutation profiles of human tumors with gene networks to stratify tumors into biologically and clinically relevant subtypes. The method is applied to ovarian, uterine and lung cancers. See also: News and Views by Raphael Orthogonal Cas9 proteins for RNA-guided gene regulation and editing   pp1116 - 1121 Kevin M Esvelt, Prashant Mali, Jonathan L Braff, Mark Moosburner, Stephanie J Yaung et al. doi:10.1038/nmeth.2681 A set of Cas9 endonucleases orthogonal to the Streptococcus pyogenes enzyme is identified. This will enable simultaneous addressing of multiple RNA-guided activities to different genomic target sites with the CRISPR-Cas9 system. Instant super-resolution imaging in live cells and embryos via analog image processing   pp1122 - 1126 Andrew G York, Panagiotis Chandris, Damian Dalle Nogare, Jeffrey Head, Peter Wawrzusin et al. doi:10.1038/nmeth.2687 An analog implementation of structured illumination using matched microlens and pinhole arrays allows up to 100-Hz 3D two-color imaging with 145-nm lateral and 350-nm axial resolution. Image-based transcriptomics in thousands of single human cells at single-molecule resolution   pp1127 - 1133 Nico Battich, Thomas Stoeger and Lucas Pelkmans doi:10.1038/nmeth.2657 An automated experimental and software pipeline for large-scale FISH enables spatial transcriptomics in thousands of single human cells at single-molecule resolution. Advertisement Only TGX Stain-Free™ Precast Gels give you visual checkpoints throughout the western blotting process. See the Workflow Comparison and download the Tech Notes to learn more about these innovative gels.    Application Note Top Trypsin/Lys-C protease mix for enhanced protein mass spectrometry analysis    Sergei Saveliev, Mark Bratz, Roman Zubarev, Matt Szapacs, Marjeta Urh et al. Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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