Table of contents



DNA profiling in India p995


The Indian parliament will soon discuss a bill regarding forensic DNA profiling, the terms of which will affect a vast population. It should not pass without substantial national debate and a provision for independent oversight.


This Month

The Author File:  Uwe Sauer p997

Vivien Marx


How to make cells spill their metabolic guts in high-throughput, and why work does not feel like work.

Points of Significance:  Simple linear regression pp999 - 1000

Naomi Altman & Martin Krzywinski



Correspondence web-based RNA-seq data analysis and visualization p1001

Jonathan L Schmid-Burgk & Veit Hornung


TransVar: a multilevel variant annotator for precision genomics pp1002 - 1003

Wanding Zhou, Tenghui Chen, Zechen Chong, Mary A Rohrdanz, James M Melott, Chris Wakefield, Jia Zeng, John N Weinstein, Funda Meric-Bernstam, Gordon B Mills & Ken Chen


Avoiding abundance bias in the functional annotation of posttranslationally modified proteins pp1003 - 1004

Christian Schölz, David Lyon, Jan C Refsgaard, Lars Juhl Jensen, Chunaram Choudhary & Brian T Weinert



Research Highlights

The strain in metagenomics p1005

Two computational tools extract strain-level information from reams of microbial sequence data.

Super-resolution in live cells pp1006 - 1007

Two strategies improve structured illumination microscopy for use in live-cell super-resolution imaging.

Targeting spines pp1006 - 1007

A new probe allows for optical erasure of newly activated dendritic spines.

Pressuring neurons into action p1008

An alternative to optogenetics, sonogenetics uses ultrasound to mechanically stimulate neurons.

Ancient protein complexes revealed p1011

A systematic analysis of protein-complex composition across a billion years of evolution reveals a spectrum of conservation.

How kinases attack signaling networks p1013

Two computational tools find residues that determine the specificity of any kinase and the effects of mutations in these residues on the phenotype of cancer cells.

Methods in Brief

Tools in Brief


Technology Feature

Nanopores: a sequencer in your backpack pp1015 - 1018

Vivien Marx


It's been a long wait for nanopore sequencing technology. Over 1,000 labs are testing the first commercial device and publishing results. Researchers tell Nature Methods about their experiences putting these early instruments through their paces. And more technology is in the works.


News and Views

Detecting nano-scale protein clustering pp1019 - 1020

David Baddeley


Two approaches for robust, objective segmentation of single-molecule localization data promise better quantitative insights into protein clustering from super-resolution imaging methods.

See also: Article by Levet et al. | Article by Rubin-Delanchy et al.




Focused ion beams in biology pp1021 - 1031

Kedar Narayan & Sriram Subramaniam


Applications of focused ion beams for biological ultrastructure and chemical imaging, with a particular emphasis on the coupling of this technology with scanning electron microscopy, are discussed in this Review.



Comparing the performance of biomedical clustering methods pp1033 - 1038

Christian Wiwie, Jan Baumbach & Richard Röttger


This analysis compares 13 clustering methods on 24 data sets using the freely accessible ClustEval platform and presents guidelines for how to choose tools and set parameters for clustering biomedical data



Whole-brain activity mapping onto a zebrafish brain atlas pp1039 - 1046

Owen Randlett, Caroline L Wee, Eva A Naumann, Onyeka Nnaemeka, David Schoppik, James E Fitzgerald, Ruben Portugues, Alix M B Lacoste, Clemens Riegler, Florian Engert & Alexander F Schier


Z-Brain is an atlas of the larval zebrafish brain. It can be combined with pERK-based neural-activity measurements from freely behaving zebrafish to identify brain regions involved in generating behavior.


Brief Communications

Bisulfite-free, base-resolution analysis of 5-formylcytosine at the genome scale pp1047 - 1050

Bo Xia, Dali Han, Xingyu Lu, Zhaozhu Sun, Ankun Zhou, Qiangzong Yin, Hu Zeng, Menghao Liu, Xiang Jiang, Wei Xie, Chuan He & Chengqi Yi


Chemical modification of 5fC allows its enrichment and genome-wide profiling at single-nucleotide resolution.

Cas9 gRNA engineering for genome editing, activation and repression pp1051 - 1054

Samira Kiani, Alejandro Chavez, Marcelle Tuttle, Richard N Hall, Raj Chari, Dmitry Ter-Ovanesyan, Jason Qian, Benjamin W Pruitt, Jacob Beal, Suhani Vora, Joanna Buchthal, Emma J K Kowal, Mohammad R Ebrahimkhani, James J Collins, Ron Weiss & George Church


The length of a single guide RNA (gRNA) determines the function of Cas9. In this study 20-nt gRNAs allowed nuclease activity and genome editing, whereas 14-nt gRNAs mediated transcriptional activation or repression.

Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling pp1055 - 1057

Kilian V M Huber, Karin M Olek, André C Müller, Chris Soon Heng Tan, Keiryn L Bennett, Jacques Colinge & Giulio Superti-Furga


A method for profiling alterations in protein thermal stability after ligand binding using mass spectrometry identifies the cellular protein targets of drugs and metabolites in living cells.

Interactive analysis and assessment of single-cell copy-number variations pp1058 - 1060

Tyler Garvin, Robert Aboukhalil, Jude Kendall, Timour Baslan, Gurinder S Atwal, James Hicks, Michael Wigler & Michael C Schatz


Gingko is an open-source, flexible, comprehensive and user-friendly web tool for analysis of single-cell copy-number variations.

WASP: allele-specific software for robust molecular quantitative trait locus discovery pp1061 - 1063

Bryce van de Geijn, Graham McVicker, Yoav Gilad & Jonathan K Pritchard


The WASP suite of open-source tools performs unbiased allele-specific sequence read mapping and provides improved power for molecular QTL discovery.



SR-Tesseler: a method to segment and quantify localization-based super-resolution microscopy data pp1065 - 1071

Florian Levet, Eric Hosy, Adel Kechkar, Corey Butler, Anne Beghin, Daniel Choquet & Jean-Baptiste Sibarita


This paper reports a method, including software, for image segmentation and cluster analysis of localization-based super-resolution data.

Bayesian cluster identification in single-molecule localization microscopy data pp1072 - 1076

Patrick Rubin-Delanchy, Garth L Burn, Juliette Griffié, David J Williamson, Nicholas A Heard, Andrew P Cope & Dylan M Owen


This paper reports a Bayesian approach for the automatic identification of the optimal clustering proposal in the analysis of single-molecule localization-based super-resolution data.

Single Molecule Cluster Analysis dissects splicing pathway conformational dynamics pp1077 - 1084

Mario R Blanco, Joshua S Martin, Matthew L Kahlscheuer, Ramya Krishnan, John Abelson, Alain Laederach & Nils G Walter


Single Molecule Cluster Analysis (SiMCAn) is a hierarchical clustering method that enables rapid interpretation of the complex single-molecule dynamic behaviors of cellular machines (such as the spliceosome) from single-molecule fluorescence resonance energy transfer data.

DNA sense-and-respond protein modules for mammalian cells pp1085 - 1090

Shimyn Slomovic & James J Collins


A zinc finger–based modular DNA sequence–recognition system produces a customizable response signal that can induce apoptosis or detect virus-infected cells.

Real-time metabolome profiling of the metabolic switch between starvation and growth pp1091 - 1097

Hannes Link, Tobias Fuhrer, Luca Gerosa, Nicola Zamboni & Uwe Sauer


With a method involving the rapid injection of living cells into a mass spectrometer, researchers demonstrate the ability to monitor metabolite profiles in real time over the course of several hours.




Corrigendum: Reporters for sensitive and quantitative measurement of auxin response p1098

Che-Yang Liao, Wouter Smet, Geraldine Brunoud, Saiko Yoshida, Teva Vernoux & Dolf Weijers


Corrigendum: Bayesian statistics p1098

Jorge López Puga, Martin Krzywinski & Naomi Altman


Corrigendum: Comparative visualization of genotype-phenotype relationships p1098

Gagarine Yaikhom, Hugh Morgan, Duncan Sneddon, Ahmad Retha, Julian Atienza-Herrero, Andrew Blake, James Brown, Armida Di Fenza, Tanja Fiegel, Neil Horner, Natalie Ring, Luis Santos, Henrik Westerberg, Steve D M Brown & Ann-Marie Mallon


Corrigendum: A holidic medium for Drosophila melanogaster p1098

Matthew D W Piper, Eric Blanc, Ricardo Leitão-Gonçalves, Mingyao Yang, Xiaoli He, Nancy J Linford, Matthew P Hoddinott, Corinna Hopfen, George A Soultoukis, Christine Niemeyer, Fiona Kerr, Scott D Pletcher, Carlos Ribeiro & Linda Partridge



Application Notes