Tuesday, May 30, 2017

Nature Methods Contents: June 2017 Volume 14 pp 541 - 635

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Nature Methods

What Factor can have a Profound Effect on a Multitude of Phenotypes?

Discover what the real impact of rodent diet on the microbiome and gut health research is.

Explore data to help you choose appropriate experimental and control diets.

View the free webinar on rodent diets and how they can shape experimental outcomes.

June 2017 Volume 14, Issue 6

In This Issue
This Month
Research Highlights
Technology Feature
News and Views
Brief Communications
Application Note

Rapid, real-time T cell activation assay

Tired of waiting for T cell activation results? Accelerate your analysis with Agilent Seahorse XF technology. The XFp analyzer detects real-time T cell activation response within minutes with CD3/CD28 immunogenic beads by measuring discrete changes in cellular glycolysis. 

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Focus on Disease models: reproducibility and translation

Lab Animal, a Nature Research journal focusing on in vivo methods, research and technology with model organisms of human health & disease, presents a special Focus on reproducibility and translation of in vivo research with disease models. 

Access this Focus >

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In This Issue


In This Issue   




CRISPR standards   p541
With the ever-expanding use of CRISPR technology, the development of standards to quantitatively benchmark on- and off-target activity needs to keep pace.


This Month


The Author File: Yannick Doyon   p543
Vivien Marx
Teamwork on and off the ice, and tipping the odds to find CRISPR hits sans markers.


Points of Significance: Clustering   pp545 - 546
Naomi Altman and Martin Krzywinski
Clustering finds patterns in data—whether they are there or not.




Unexpected mutations after CRISPR-Cas9 editing in vivo   pp547 - 548
Kellie A Schaefer, Wen-Hsuan Wu, Diana F Colgan, Stephen H Tsang, Alexander G Bassuk et al.


Digenome-seq web tool for profiling CRISPR specificity   pp548 - 549
Jeongbin Park, Liam Childs, Daesik Kim, Gue-Ho Hwang, Sunghyun Kim et al.


E-scape: interactive visualization of single-cell phylogenetics and cancer evolution   pp549 - 550
Maia A Smith, Cydney B Nielsen, Fong Chun Chan, Andrew McPherson, Andrew Roth et al.


Research Highlights


GPCR interactions in space and time
A proximity labeling technique yields new insights into GPCR signaling.

Good vibrations for super-multiplexed imaging
Researchers optimize stimulated Raman scattering microscopy and combine it with a new panel of Raman-active dyes to enable 24-color bioimaging.

CRISPR's paper test
A spot of CRISPR protein on paper provides a powerful diagnostic assay.

Extending pluripotency with a cocktail
A chemical combination enables culture of pluripotent cells.

Microfetti: a fate-mapping system for microglia
A multicolor reporter mouse model enables monitoring of the fate and dynamics of microglia in health and disease.

Methods in Brief

Engineering complex and robust genetic circuits | Track first and identify later | Single genome amplification goes linear | Chip-based nanoscopy

Tools in Brief

GPCR function insights by cryo-EM | Deep learning improves image analysis | Building a better TRAP for translation | Electrophysiology in intact Caenorhabditis elegans

JOBS of the week
Postdoctoral Fellows in Statistical Genetics / Computational Biology
Columbia University
Bioinformatician or Statistician for Genomics, Systems Biology and mining of Big clinical data in brain disorders: A collaboration between University of Copenhagen (DK) and the Broad Institute (US)
Capital Region of Denmark
Postdoctoral Fellowships in Computational Chemistry and Physics
D. E. Shaw Research
Bioinformatic Postdoc
Rutgers, the State University of New Jersey
Postdoctoral position in chemical biology
Ecole Normale Superieure (ENS Paris)
More Science jobs from
NETTAB 2017 Methods, tools & platforms for Personalized Medicine in the Big Data Era
Palermo, Italy
More science events from

Technology Feature


Organoids: a better in vitro model   pp559 - 562
Katherine Ellen Foley
3D human cell cultures are changing the way scientists model organ development and function—but they have their own set of complications.


News and Views


Cas9 in action: no more known unknowns?   pp563 - 564
Fyodor D Urnov
Useful new methods are being introduced to experimentally determine the genome-wide consequences of Cas9-based editing.

See also: Article by Cameron et al. | Article by Tsai et al.




Normalizing single-cell RNA sequencing data: challenges and opportunities   pp565 - 571
Catalina A Vallejos, Davide Risso, Antonio Scialdone, Sandrine Dudoit and John C Marioni
This Perspective examines single-cell RNA-seq data challenges and the need for normalization methods designed specifically for single-cell data in order to remove technical biases.


Brief Communications


Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions   pp573 - 576
John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham et al.
A library of plasmids expressing two gRNAs allows for the mapping of combinatorial genetic interactions with the CRISPR system. Results in cancer cells suggest that cellular context is an important factor for the interaction network.


Genetic interaction mapping in mammalian cells using CRISPR interference   pp577 - 580
Dan Du, Assen Roguev, David E Gordon, Meng Chen, Si-Han Chen et al.
CRISPR interference screens with pairs of sgRNAs allow for quantitative characterization of genetic interactions.


Large-field-of-view imaging by multi-pupil adaptive optics   pp581 - 583
Jung-Hoon Park, Lingjie Kong, Yifeng Zhou and Meng Cui
Adaptive optics can counteract optical aberrations within tissues, but the field of view is typically limited. Multi-pupil adaptive optics expands the area that can be imaged, and this is demonstrated by multiple applications in the mouse brain imaging.


SCnorm: robust normalization of single-cell RNA-seq data   pp584 - 586
Rhonda Bacher, Li-Fang Chu, Ning Leng, Audrey P Gasch, James A Thomson et al.
SCnorm normalizes single-cell RNA-seq data for improved downstream analyses such as differential expression and cell-state discrimination.


ModelFinder: fast model selection for accurate phylogenetic estimates   pp587 - 589
Subha Kalyaanamoorthy, Bui Quang Minh, Thomas K F Wong, Arndt von Haeseler and Lars S Jermiin
ModelFinder is a fast model-selection method that greatly improves the accuracy of phylogenetic estimates.


Genome-wide profiling of heritable and de novo STR variations   pp590 - 592
Thomas Willems, Dina Zielinski, Jie Yuan, Assaf Gordon, Melissa Gymrek et al.
HipSTR accurately genotypes and phases short tandem repeats, enabling robust genome-wide analyses of short tandem repeat variations.

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Iterative expansion microscopy   pp593 - 599
Jae-Byum Chang, Fei Chen, Young-Gyu Yoon, Erica E Jung, Hazen Babcock et al.
Iterative expansion microscopy (iExM) is a strategy that achieves high resolution expansion microscopy by expanding samples multiple times. Expanding a sample twice enables ∼4.5 × 4.5 ∼20× physical expansion and ∼25 nm resolution.


Mapping the genomic landscape of CRISPR-Cas9 cleavage   pp600 - 606
Peter Cameron, Chris K Fuller, Paul D Donohoue, Brittnee N Jones, Matthew S Thompson et al.
SITE-Seq probes Cas9 cleavage sites in vitro and returns a comprehensive list of off-target sites at different Cas9-sgRNA concentrations.

See also: News and Views by Urnov

CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets   pp607 - 614
Shengdar Q Tsai, Nhu T Nguyen, Jose Malagon-Lopez, Ved V Topkar, Martin J Aryee et al.
CIRCLE-seq is an in vitro assay for selectively sequencing off-target sites cleaved by Cas9-sgRNA in genomic DNA. It sensitively profiles genome-wide off-target cut sites and characterizes the contribution of SNPs to these cleavage events.

See also: News and Views by Urnov

Marker-free coselection for CRISPR-driven genome editing in human cells   pp615 - 620
Daniel Agudelo, Alexis Duringer, Lusiné Bozoyan, Caroline C Huard, Sophie Carter et al.
A gain-of-function mutation in a sodium/potassium pump renders cells resistant to a small-molecule drug and provides an efficient coselection strategy to enrich for CRISPR-induced mutations at an independent locus.


Generation of pure GABAergic neurons by transcription factor programming   pp621 - 628
Nan Yang, Soham Chanda, Samuele Marro, Yi-Han Ng, Justyna A Janas et al.
Transient transcription factor expression rapidly induces a homogenous population of mature GABAergic neurons from human pluripotent stem cells, aiding the study of inhibitory neuron function and disease.


A tiling-deletion-based genetic screen for cis-regulatory element identification in mammalian cells   pp629 - 635
Yarui Diao, Rongxin Fang, Bin Li, Zhipeng Meng, Juntao Yu et al.
CREST-seq allows functional screening of cis-regulatory elements through the use of sgRNA pairs to introduce tiled deletions in regions of interest. The analysis of a 2-megabase target region shows that promoters can act as distal enhancers for unrelated genes.

Nature Milestones: Interactive antibody timeline 

Nature Milestones: Antibodies presents an interactive timeline on the history of antibodies covering everything from their initial description in antisera through to their application in immunotherapy. The timeline includes written content, video interviews and animations.

Access the timeline free online

Produced with support from

Application Note


A humanized phenotypic screening platform for chronic pain   
Daniel Tams, Paul Karila and Ashley Barnes

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