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May 2018 Volume 15, Issue 5

This Month
Research Highlights
Technology Feature
News and Views
Brief Communications
Application Note
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Mapping the human   p299
The Human Cell Atlas, driven by a collaborative spirit and rapid advances in single-cell methods, is poised to advance both biological understanding and technical development.

This Month


Harris Wang   p301
Vivien Marx
A regulatory vocabulary for synthetic biology and why baby diapers matter.



What's in a sample? Increasing transparency in biospecimen procurement methods   pp303 - 304
Joshua LaBaer, Joseph F Miceli III and Leonard P Freedman

ATAC Primer Tool for targeted analysis of accessible chromatin   pp304 - 305
Kathryn E Yost, Ava C Carter, Jin Xu, Ulrike Litzenburger and Howard Y Chang

Computational correction of index switching in multiplexed sequencing libraries   pp305 - 307
Anton J M Larsson, Geoff Stanley, Rahul Sinha, Irving L Weissman and Rickard Sandberg

Research Highlights


AI transforms image reconstruction
A deep-learning-based approach improves the speed, accuracy, and robustness of biomedical image reconstruction.

A nontoxic rabies virus for neural circuit mapping
A double-deletion rabies virus variant overcomes the cytotoxicity that has previously limited long-term applications for retrograde labeling of projection neurons.

Correlation analysis in single-molecule localization microscopy
A coordinate-based framework quantifies the correlation and interaction of biomolecules in images acquired with super-resolution microscopy techniques.

CasRx is a programmable CRISPR-Cas system that targets RNA for efficient knockdown and splicing modulation.

A MACnificent view of the cellular protein landscape
The multipurpose MAC-tag enables integrative interaction proteomics to localize proteins with sub-organelle precision.

Methods in Brief

Following fitness after mutations in single cells    | Chronic imaging of the fruit fly brain    | Clearing the way for imaging of the human brain    | Extracting neuronal activity from microendoscopy videos   

Tools in Brief

Expanding the range of base editors    | cisTEM software for cryo-EM    | GFP goes sour    | Metabolomes from metagenomics and modeling   

JOBS of the week
Staff scientist - Proteomics
Weizmann Institute of Science
AOI Biosensing Chair Position
University of Missouri (MU) College of Engineering
Bioinformatics Specialist
Massachusetts General Hospital
Systems Biologist
Columbia University Medical Center
Postdoctoral Scholar
Oregon Health & Science University and Knight Cancer Institute
More Science jobs from
G19 Statistics for Non Statisticians
Maidenhead, UK
More science events from

Technology Feature


Microbiology: making the best of PCR bias   pp317 - 320
Michael Eisenstein
Many factors can skew the results of a widely used amplification technique for microbiome analysis, but researchers are finding strategies for getting at the truth.

News and Views


Sorting apples from oranges in single-cell expression comparisons   pp321 - 322
Fiona K Hamey and Berthold Gottgens
Two methods for comparing single-cell expression data sets help address the challenge of integrating data across conditions and experiments.



Metagenomic mining of regulatory elements enables programmable species-selective gene expression   pp323 - 329
Nathan I Johns, Antonio L C Gomes, Sung Sun Yim, Anthony Yang, Tomasz Blazejewski et al.
Metagenomic mining generates a rich resource of regulatory sequences with species-selective and universal activity, making it possible to engineer synthetic circuits with tunable gene expression across diverse bacterial hosts.

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors   pp330 - 338
Anand Venkataraman, Kun Yang, Jose Irizarry, Mark Mackiewicz, Paolo Mita et al.
A collection of 1,406 high-quality, immunoprecipitation- and immunoblotting-grade monoclonal antibodies to 737 human transcription factors is made available as a community resource, along with all validation data.

Brief Communications


Identification of spatial expression trends in single-cell gene expression data   pp339 - 342
Daniel Edsgard, Per Johnsson and Rickard Sandberg
trendsceek identifies genes with significant spatial trends in single-cell spatial expression data, as well as in low-dimensional projections of dissociated single-cell RNA-seq data.

SpatialDE: identification of spatially variable genes   pp343 - 346
Valentine Svensson, Sarah A Teichmann and Oliver Stegle
SpatialDE identifies genes with significant spatial expression patterns from multiplexed imaging or spatial RNA-sequencing data, and can cluster genes with similar spatial patterns as a form of expression-based tissue histology.

Photoactivatable drugs for nicotinic optopharmacology   pp347 - 350
Sambashiva Banala, Matthew C Arvin, Nicholas M Bannon, Xiao-Tao Jin, John J Macklin et al.
Optopharmacological manipulation with /`caged/' glutamate and GABA has enabled the study of these ligands/' cognate receptors, but other ligands such as tertiary amine drugs have not been amenable to caging. A new strategy yields a photoactivatable nicotine, PA-Nic, which allows manipulation of nicotinic acetylcholine receptors.

NAMD goes quantum: an integrative suite for hybrid simulations   pp351 - 354
Marcelo C R Melo, Rafael C Bernardi, Till Rudack, Maximilian Scheurer, Christoph Riplinger et al.
The integration of quantum chemistry and molecular dynamics programs coupled with a graphical user interface provides a streamlined tool for powerful simulations of biomolecular reaction mechanisms.

Real-time fluorescence and deformability cytometry   pp355 - 358
Philipp Rosendahl, Katarzyna Plak, Angela Jacobi, Martin Kraeter, Nicole Toepfner et al.
RT-FDC combines the specificity of fluorescent probes with functional readout of a cell's mechanical properties. The resulting correlation of fluorescence-based cell identity with mechanical measurements in real time allows the development of label-free, mechanical cell sorting.

scmap: projection of single-cell RNA-seq data across data sets   pp359 - 362
Vladimir Yu Kiselev, Andrew Yiu and Martin Hemberg
scmap enables the comparison of disparate single-cell RNA-seq data sets by projecting individual cells or clusters from a query sample onto a reference sample or cell atlas.

Improved Ribo-seq enables identification of cryptic translation events   pp363 - 366
Florian Erhard, Anne Halenius, Cosima Zimmermann, Anne L'Hernault, Daniel J Kowalewski et al.
PRICE uses Ribo-seq data to predict ORFs and start codons with high accuracy by computationally eliminating experimental noise and dissecting overlapping translation events.

Real-time 3D single-molecule localization using experimental point spread functions   pp367 - 369
Yiming Li, Markus Mund, Philipp Hoess, Joran Deschamps, Ulf Matti et al.
An open-source, real-time fitter for 3D single-molecule localization microscopy uses experimental point spread functions. This enables accurate 3D super-resolution microscopy on standard microscopes without dedicated 3D optics.


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Specter: linear deconvolution for targeted analysis of data-independent acquisition mass spectrometry proteomics   pp371 - 378
Ryan Peckner, Samuel A Myers, Alvaro Sebastian Vaca Jacome, Jarrett D Egertson, Jennifer G Abelin et al.
Data-independent-acquisition-based mass spectrometry enables highly reproducible proteome analysis, but results interpretation is challenging owing to the complex nature of the spectral data. A software tool, Specter, effectively resolves spectra for highly similar peptides.

FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data   pp379 - 386
Josip S Herman,  Sagar and Dominic Grun
FateID identifies fate biases in early multipotent progenitor populations from single-cell RNA-seq data.

Burden-driven feedback control of gene expression   pp387 - 393
Francesca Ceroni, Alice Boo, Simone Furini, Thomas E Gorochowski, Olivier Borkowski et al.
In this CRISPR-based feedback control system, sgRNA expression is triggered by the burden of protein overexpression, and the sgRNA directs repression of the exogenous gene promoter to reduce burdensome expression and restore growth of the cell.

Animation on CRISPR: Gene editing and beyond

The CRISPR-Cas9 system has revolutionised gene editing, but cutting DNA isn't all it can do. This Animation, from Nature Methods, explores where CRISPR might be headed next.

Watch the Animation here>>

Produced with support from: 



Retraction: Unexpected mutations after CRISPR-Cas9 editing in vivo   p394
Kellie A Schaefer, Wen-Hsuan Wu, Diana F Colgan, Stephen H Tsang, Alexander G Bassuk et al.

Application Note


TwistAmp[reg] Liquid: a versatile amplification method to replace PCR   
Oliver W Stringer, Jennifer M Andrews, Hazel L Greetham and Matthew S Forrest




Corrigendum: RNA-protein interaction detection in living cells   p394
Muthukumar Ramanathan, Karim Majzoub, Deepti S Rao, Poornima H Neela, Brian J Zarnegar et al.

Corrigendum: CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets   p394
Shengdar Q Tsai, Nhu T Nguyen, Jose Malagon-Lopez, Ved V Topkar, Martin J Aryee et al.

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