Nature Methods Contents: September 2016 Volume 13 pp 699 - 798

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Advertisement Extend the boundaries of cellular imaging with the newest super-resolution systems from Nikon. N-STORM 4.0 features z-stacking and 10-fold improved acquisition speed. N-SIM E is a streamlined structured illumination system, offering twice the resolution of a conventional microscope at about half the cost of other SIM systems. For more information, visit www.nikoninst.com/nature/super-resolution TABLE OF CONTENTS September 2016 Volume 13, Issue 9 In This Issue Editorial This Month Correspondence Research Highlights Technology Feature News and Views Perspectives Brief Communications Articles Advertisement   Are you working with valuable protein or nucleic acid samples in a low concentration or amount? To ensure that you are not losing sample material during transportation or storage, Eppendorf offers Tubes and Pipette Tips with special surface properties, such as LoBind or LoRetention. Have a closer look at our laboratory consumables to get more information. Click here    Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Secreted Luciferase Reporter for Live Cell Analysis Secreted luciferase assays: Gaussia Luciferase (GLuc) and Secreted Alkaline Phosphatase (SEAP) enable live cell analysis Reporter vectors and clones: Cloning vectors Promoter reporter clones 3' UTR miRNA target clones Transcriptional response element reporter clones Learn more >>   Advertisement Free Naturejobs Career Expo London Registration is now open for the free Naturejobs Career Expo London on September 16, 2016. Be sure to attend this special 10 year anniversary of the London science career fair for your chance to meet employers face-to-face, attend all conferences and workshops, take part in our photo booth fun, win amazing prizes and so much more!  Register Free today!   Advertisement NEURAL CIRCUITRY OF EMOTION Presented by: Shenzhen Institutes of Advanced Technology, CAS | McGovern Institute for Brain Research at MIT | Nature Neuroscience November 2-4, 2016 | Shenzhen, China REGISTER NOW!   In This Issue Top In This Issue    Editorial Top Database under maintenance   p699 doi:10.1038/nmeth.3996 Managing the growth in biomedical data requires coordinated strategies and a strong financial commitment by funders and institutions. This Month Top The Author File: Tim R. Mercer   p701 Vivien Marx doi:10.1038/nmeth.3962 Sequins can help labs see how well a sequencing experiment is going. Surfing experiments are another matter. Points of Significance: Model selection and overfitting   pp703 - 704 Jake Lever, Martin Krzywinski and Naomi Altman doi:10.1038/nmeth.3968 With four parameters I can fit an elephant and with five I can make him wiggle his trunk. —John von Neumann Correspondence Top Impact of outdated gene annotations on pathway enrichment analysis   pp705 - 706 Lina Wadi, Mona Meyer, Joel Weiser, Lincoln D Stein and Juri Reimand doi:10.1038/nmeth.3963 Research Highlights Top Nanoscopy for the whole cell Researchers plumb the depths of the cell with volumetric 4Pi nanoscopy. Spatial transcriptomics By capturing and barcoding RNA in its native tissue location, researchers can visualize and quantify gene expression in situ. Tracing cell lineage with 5hmC Single-cell 5hmC sequencing uncovers cell-to-cell differences in the two DNA strands of a given chromosome. The human proteome on target SRMAtlas contains mass spectrometry assays allowing targeted analysis of nearly 100% of human proteins. Teaching nanopores to speak protein A proof-of-concept platform demonstrates the feasibility of nanopore-based sequencing of polypeptide chains. NBLAST: a similarity search for neurons By analogy to protein and DNA similarity searches, NBLAST provides a fast and efficient way of finding morphological similarities between neurons. Automating brain mapping Two new platforms allow single neurons to be imaged throughout the mouse brain. Methods in Brief Are super-enhancers really super? | Imaging chromosome organization | Model colons | Expanding expansion microscopy Tools in Brief Cell-specific proteomics with SORT-E | An expression atlas of the developing macaque brain | Showdown between Cas9 and Cpf1 | Super-resolution imaging in live fly larvae with RESOLFT Methods JOBS of the week PhD Studentship Institute for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke University, Magdeburg Germany Research Group Leader Chica and Heinz Schaller Foundation (CHS) Postdoctoral Research Scientist Columbia University Research Professional 1 University of Chicago Senior Research Staff and Postdoc Positions at University of Vienna University of Vienna (Universitaet Wien) More Science jobs from Technology Feature Top Proteomics: taking on protein complexes   pp721 - 727 Vivien Marx doi:10.1038/nmeth.3966 News and Views Top Exploiting the cyanobacterial light-harvesting machinery for developing fluorescent probes   pp729 - 730 Atsushi Miyawaki doi:10.1038/nmeth.3983 Researchers develop a new class of near-infrared fluorescent proteins from a light-harvesting phycobiliprotein. See also: Article by Rodriguez et al. Perspectives Top The Perseus computational platform for comprehensive analysis of (prote)omics data   pp731 - 740 Stefka Tyanova, Tikira Temu, Pavel Sinitcyn, Arthur Carlson, Marco Y Hein et al. doi:10.1038/nmeth.3901 Perseus is a comprehensive, user-friendly software platform for the biological analysis of quantitative proteomics data. It is intended to help biologists with little bioinformatics training to interpret protein expression, post-translational modification and interaction data. Also in this issue, see the Perspective by Rost et al. OpenMS: a flexible open-source software platform for mass spectrometry data analysis   pp741 - 748 Hannes L Rost, Timo Sachsenberg, Stephan Aiche, Chris Bielow, Hendrik Weisser et al. doi:10.1038/nmeth.3959 OpenMS is a flexible, user-friendly, open-source software platform for the biological analysis of mass spectrometry proteomics and metabolomics data. The modular platform allows developers to seamlessly generate custom data-analysis workflows and directly make such ready-made workflows available to biologist end-users. Also in this issue, see the Perspective by Tyanova et al. Brief Communications Top Real-time selective sequencing using nanopore technology   pp751 - 754 Matthew Loose, Sunir Malla and Michael Stout doi:10.1038/nmeth.3930 Read Until allows real-time selective sequencing on a nanopore sequencer, enabling applications such as target enrichment and amplicon normalization. LOVTRAP: an optogenetic system for photoinduced protein dissociation   pp755 - 758 Hui Wang, Marco Vilela, Andreas Winkler, Miroslaw Tarnawski, Ilme Schlichting et al. doi:10.1038/nmeth.3926 LOVTRAP enables rapid optogenetic control of protein dissociation and is complementary to related optogenetic tools that mediate light-induced protein association. LOVTRAP is applied to the study of oscillatory processes at the cell membrane. Virtual microfluidics for digital quantification and single-cell sequencing   pp759 - 762 Liyi Xu, Ilana L Brito, Eric J Alm and Paul C Blainey doi:10.1038/nmeth.3955 Virtual microfluidics uses hydrogel entrapment to make high-throughput single-cell and single-molecule amplification broadly accessible without the need for special equipment. Advertisement IntelliQube® - Integrated PCR Workflow - 1.2-Fold Resolution   TATAA Biocenter evaluated the IntelliQube, a fully automated medium to high throughput PCR instrument integrating liquid handling, thermal cycling and detection, while leveraging miniaturized reaction volumes (1.6 µL) in Array Tape®. Results showed the IntelliQube was able to resolve 1.2-fold changes with greater than 97% sensitivity. Download the application note   Articles Top A far-red fluorescent protein evolved from a cyanobacterial phycobiliprotein   pp763 - 769 Erik A Rodriguez, Geraldine N Tran, Larry A Gross, Jessica L Crisp, Xiaokun Shu et al. doi:10.1038/nmeth.3935 A bright and photostable far-red fluorescent protein, smURFP, was developed from a cyanobacterial phycobiliprotein. smURFP uniquely binds a highly cell-permeable biliverdin derivative to obtain fluorescence brightness comparable to that of eGFP in cells. See also: News and Views by Miyawaki Revealing disease-associated pathways by network integration of untargeted metabolomics   pp770 - 776 Leila Pirhaji, Pamela Milani, Mathias Leidl, Timothy Curran, Julian Avila-Pacheco et al. doi:10.1038/nmeth.3940 A network-based method and computational tool, PIUMet, reveals disease-associated molecular pathways from untargeted metabolomics data without requiring mass-spectral feature identification. TRIC: an automated alignment strategy for reproducible protein quantification in targeted proteomics   pp777 - 783 Hannes L Rost, Yansheng Liu, Giuseppe D'Agostino, Matteo Zanella, Pedro Navarro et al. doi:10.1038/nmeth.3954 TRIC, a cross-run alignment algorithm and software tool, enables reproducible quantification of thousands of peptides across multiple targeted liquid chromatography-tandem mass spectrometry runs. Representing genetic variation with synthetic DNA standards   pp784 - 791 Ira W Deveson, Wendy Y Chen, Ted Wong, Simon A Hardwick, Stacey B Andersen et al. doi:10.1038/nmeth.3957 Synthetic DNA spike-ins that recapitulate genetic variation present in human genomes serve as quantitative and qualitative controls for genome sequencing and variant detection. Spliced synthetic genes as internal controls in RNA sequencing experiments   pp792 - 798 Simon A Hardwick, Wendy Y Chen, Ted Wong, Ira W Deveson, James Blackburn et al. doi:10.1038/nmeth.3958 Synthetic spike-in standards ('sequins'), representing spliced mRNA isoforms, provide internal controls for assessing transcript assembly and quantification within and between RNA sequencing libraries. Sequins representing fused genes can be used to determine the sensitivity limit for oncogenic fusions in cancer samples. 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