Thursday, June 29, 2017

Nature Methods Contents: July 2017 Volume 14 pp 637 - 752

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July 2017 Volume 14, Issue 7

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

Detect and Modulate T Cell Activation in Real Time.

See for yourself how it can be used to optimize CAR T durability. The Agilent Seahorse XFp analyzer detects real-time T cell activation response within minutes with CD3/CD28 immunogenic beads by measuring discrete changes in cellular glycolysis. Accelerate you analysis with XF technology.

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Recommend to library

Inspiration does not obey speed limits.

Announcing the ORCA-Lightning from Hamamatsu.
Our new 12MP sCMOS camera engineered for high
speed and low noise and ready for Lightsheet
Nature Index China 2017

China continues to increase its global share of research papers, but publication numbers are just one indicator that a country's science is thriving.

Read the full supplement free for six months

A supplement to Nature Biotechnology | Nature Medicine | Nature Reviews Drug Discovery

Medtech Dealmakers explores the dealmaking strategies of the growing medical technology industry, and provides in-depth analysis of emerging technologies, as well as showcase innovative companies seeking partners. Check out the latest issue for medtech dealmaking and financing trends in 2016, and diagnostics deals from the past year- particularly for immuno oncology applications.

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In This Issue


In This Issue   




Seeing red   p637
The growing advantages of red to near-infrared fluorescent probes should move them beyond being a 'second color' in biological imaging.


This Month


The Author File: Alexis Battle   p639
Vivien Marx
Calculating gene-environment interactions, and the role of a 'why' machine.


Points of Significance: Principal component analysis   pp641 - 642
Jake Lever, Martin Krzywinski and Naomi Altman
PCA helps you interpret your data, but it will not always find the important patterns.




Mass spectrometrists should search for all peptides, but assess only the ones they care about   pp643 - 644
Adriaan Sticker, Lennart Martens and Lieven Clement

See also: Correspondence by Noble & Keich

Response to “Mass spectrometrists should search for all peptides, but assess only the ones they care about”   p644
William Stafford Noble and Uri Keich

See also: Correspondence by Sticker et al.

ProHits-viz: a suite of web tools for visualizing interaction proteomics data   pp645 - 646
James D R Knight, Hyungwon Choi, Gagan D Gupta, Laurence Pelletier, Brian Raught et al.


PIQED: automated identification and quantification of protein modifications from DIA-MS data   pp646 - 647
Jesse G Meyer, Sushanth Mukkamalla, Hanno Steen, Alexey I Nesvizhskii, Bradford W Gibson et al.


Research Highlights


Better tools for Bacteroides
Two sets of complementary tools extend our capacity to manipulate the gut microbiome.

Charting the subcellular proteome
Human protein subcellular locations light up in the Cell Atlas resource.

CRISPR kinetics
In vitro Cas9-binding assays show the effects of mutations in the target sequence on binding kinetics.

Zooming into the larval zebrafish brain
A serial-section electron microscopy data set of larval zebrafish brain—imaged at several scales—provides a resource for structure-function analyses of the animals' neural circuitry.

Organoid variability examined
Single-cell transcriptomics is used to determine what cell types are present in brain organoids and how much these cell types vary across organoids.

Methods in Brief

Buckets of bacterial genomes | Reconciling small and large scales with FIB-SEM | Ultrafast thermal cycling | Single-protein detection by cryo-EM

Tools in Brief

Self-limiting Cas9 | Functional blood progenitors for mouse and man | The BioPlex network, 2.0 | Supramolecular assemblies for NIR II imaging

JOBS of the week
Research Fellow - Data analytics and machine learning (Bioinformatics)
University of Birmingham
Several PhD positions / one Postdoc position
Albert-Ludwigs-Universitaet Freiburg
Scientist, Molecular Interaction and Characterization – Bioanalytical Sciences (BAS)
Genentech, Inc.
Postdoctoral position in bioinformatics / computational biology
Stanford University
Post-Doctoral Fellow in Bioinformatics / Statistical Genetics
Sidra Medical and Research Centre
More Science jobs from
NETTAB 2017 Methods, tools & platforms for Personalized Medicine in the Big Data Era
Palermo, Italy
More science events from



Assessing phototoxicity in live fluorescence imaging   pp657 - 661
P Philippe Laissue, Rana A Alghamdi, Pavel Tomancak, Emmanuel G Reynaud and Hari Shroff
This Commentary discusses the problem of phototoxicity in live imaging and suggests guidelines to improve its assessment and reporting.


Towards a perceptive understanding of size in cellular biology   pp662 - 665
Monica Zoppè
This piece tackles the question of how to make biological scale more intuitive to human beings, bringing to bear the author's background in scientific visualization.


Technology Feature


Metabolism: sweeter paths in glycoscience   pp667 - 670
Vivien Marx
Carbohydrates are tough molecules to study, but glycoscientists are developing and democratizing the needed tools.


News and Views


Illuminating redox biology using NADH- and NADPH-specific sensors   pp671 - 672
Andreas Wiederkehr and Nicolas Demaurex
Genetically encoded NAD and NADP sensors will revolutionize the study of redox biology.

See also: Article by Tao et al.



FISH-ing for captured contacts: towards reconciling FISH and 3C   pp673 - 678
Geoffrey Fudenberg and Maxim Imakaev
This Analysis explores the relationship between chromosome conformation capture (for example, Hi-C) and FISH datasets, and uses simulations to reconcile measurements from the two technologies.


Comparison of computational methods for Hi-C data analysis   pp679 - 685
Mattia Forcato, Chiara Nicoletti, Koustav Pal, Carmen Maria Livi, Francesco Ferrari et al.
Six tools to call chromatin interactions and seven tools for topologically associating domain calling are systematically compared with real and simulated data. The strengths and weaknesses of each tool are discussed.


Brief Communications


Differential analysis of RNA-seq incorporating quantification uncertainty   pp687 - 690
Harold Pimentel, Nicolas L Bray, Suzette Puente, Páll Melsted and Lior Pachter
By using bootstraps that estimate inferential variance, the sleuth method and software provide fast and highly accurate differential gene expression analysis in an interactive Shiny app.


webKnossos: efficient online 3D data annotation for connectomics   pp691 - 694
Kevin M Boergens, Manuel Berning, Tom Bocklisch, Dominic Bräunlein, Florian Drawitsch et al.
webKnossos is a browser-based tracing and annotation tool for 3D electron microscopy data sets that is optimized for seamless data viewing. The tool/'s flight-mode view facilitates fast neurite tracing because of its egocentric viewpoint.


Nm-seq maps 2′-O-methylation sites in human mRNA with base precision   pp695 - 698
Qing Dai, Sharon Moshitch-Moshkovitz, Dali Han, Nitzan Kol, Ninette Amariglio et al.
Iterative oxidation, elimination and dephosphorylation steps remove nucleotides from the 3′ end of RNA until a 2′-O-methylated ribose that cannot be oxidized is encountered and brings the process to a stop. High-throughput sequencing of these fragments exposes 2′-O-methyl sites at base resolution.


Allele-specific expression reveals interactions between genetic variation and environment   pp699 - 702
David A Knowles, Joe R Davis, Hilary Edgington, Anil Raj, Marie-Julie Favé et al.
The EAGLE algorithm and software identifies replicable gene-by-environment interactions based on associations between environment and allele-specific expression.


Quantitative mRNA imaging throughout the entire Drosophila brain   pp703 - 706
Xi Long, Jennifer Colonell, Allan M Wong, Robert H Singer and Timothée Lionnet
Improved fluorescence in situ hybridization enables smFISH in cleared whole-mount Drosophila brains with confocal microscopy; a custom Bessel beam structured illumination microscope allows single-mRNA detection across the entire brain.


Testing for differential abundance in mass cytometry data   pp707 - 709
Aaron T L Lun, Arianne C Richard and John C Marioni
A statistical approach makes it possible to detect differentially abundant cell populations across biological conditions from high-dimensional mass cytometry data without relying on cell clustering.


CRISPR-STOP: gene silencing through base-editing-induced nonsense mutations   pp710 - 712
Cem Kuscu, Mahmut Parlak, Turan Tufan, Jiekun Yang, Karol Szlachta et al.
Early STOP codons created with CRISPR base editors leads to gene knockout with high efficiency and does not stress cells with double-strand DNA breaks. CRISPR-STOP can target the majority of human genes and is useful for genetic screens.

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Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice   pp713 - 719
Weijian Zong, Runlong Wu, Mingli Li, Yanhui Hu, Yijun Li et al.
FHIRM-TPM is a miniature two-photon microscope capable of imaging fluorescently labeled neurons in the brains of freely behaving mice. It allows for imaging of spines or recording of neural activity with a frame rate up to 40 Hz.


Genetically encoded fluorescent sensors reveal dynamic regulation of NADPH metabolism   pp720 - 728
Rongkun Tao, Yuzheng Zhao, Huanyu Chu, Aoxue Wang, Jiahuan Zhu et al.
Genetically encoded iNap sensors allow imaging of NADPH with high spatiotemporal resolution in living systems. The iNaps cover physiologically relevant NADPH concentrations and are demonstrated in mammalian cells and live zebrafish.

See also: News and Views by Wiederkehr & Demaurex

Biosynthesis and genetic encoding of phosphothreonine through parallel selection and deep sequencing   pp729 - 736
Michael Shaofei Zhang, Simon F Brunner, Nicolas Huguenin-Dezot, Alexandria Deliz Liang, Wolfgang H Schmied et al.
A new approach to evolve novel aminoacyl-tRNA synthetase-tRNA pairs with orthogonal substrate specificity is applied to generate a system to site-specifically incorporate phosphothreonine into proteins, enabling functional studies of this post-translational modification.


A quantitative and multiplexed approach to uncover the fitness landscape of tumor suppression in vivo   pp737 - 742
Zoë N Rogers, Christopher D McFarland, Ian P Winters, Santiago Naranjo, Chen-Hua Chuang et al.
The combination of tumor barcoding with CRISPR-mediated targeting of tumor suppressors allows quantitative analysis of tumor-suppressor function during tumor growth in vivo.


Fused cerebral organoids model interactions between brain regions   pp743 - 751
Joshua A Bagley, Daniel Reumann, Shan Bian, Julie Lévi-Strauss and Juergen A Knoblich
The fusion of patterned cerebral organoids into more complex structures enables modeling of inter-regional processes such as neuronal migration.

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 >

Produced with support from: 
Taconic Biosciences, Inc. 
Charles River



Erratum: In vivo imaging of neural activity   p752
Weijian Yang and Rafael Yuste


Erratum: Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput   p752
Todd M Gierahn, Marc H Wadsworth II, Travis K Hughes, Bryan D Bryson, Andrew Butler et al.


Erratum: Optoacoustic imaging at multiple spatiotemporal scales   p752
Rita Strack




Corrigendum: In vivo imaging of neural activity   p752
Weijian Yang and Rafael Yuste

Call for nominations: 2017 John Maddox Prize for Standing up for Science.

Recognising the work of individuals who promote science in the face of hostility. Winners will be announced at a reception in London, as well as in Nature, and will receive £2,000.

Closing date for nominations is 31st July 2017.

Click to learn more
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