Table of contents



Should scientists tell stories? p1037


A narrative can effectively communicate scientific information. But when telling a perfect story becomes an end in itself, the scientific process can be easily compromised.


This Month

The author file: Takanari Inoue p1039

Vivien Marx


Sensors show calcium movement in tiny, cellular antennae.

Points of significance: Significance, P values and t-tests pp1041 - 1042

Martin Krzywinski & Naomi Altman


The P value reported by tests is a probabilistic significance, not a biological one.



Reply to: "Against storytelling of scientific results" p1046

Martin Krzywinski & Alberto Cairo


See also: Correspondence by Katz

TCPA: a resource for cancer functional proteomics data Open pp1046 - 1047

Jun Li, Yiling Lu, Rehan Akbani, Zhenlin Ju, Paul L Roebuck, Wenbin Liu, Ji-Yeon Yang, Bradley M Broom, Roeland G W Verhaak, David W Kane, Chris Wakefield, John N Weinstein, Gordon B Mills & Han Liang


ScientiFig: a tool to build publication-ready scientific figures p1048

Benoit Aigouy & Vincent Mirouse



Research Highlights

Roadblocks to reprogramming, cleared p1051

The removal or knockdown of an epigenetic repressor, Mbd3, results in near-complete reprogramming of mouse and human somatic cells to pluripotency.

Finding function in the folds pp1052 - 1053

Single-cell modeling of chromosomal organization could help scientists untangle how genomic organization informs function and vice versa.

Modifying chromatin to shut off enhancers pp1052 - 1053

Transcription activator–like effectors (TALEs) fused to enzymes that change chromatin signatures interrogate the role of enhancers in gene expression.

A well-preserved program p1054

Genes that restore pluripotency to mature mouse cells can initiate similar reprogramming in more distantly related species.

Designer binders p1057

Researchers define rational design principles to make a small-molecule ligand-binding protein from scratch.

When rodents run the research p1059

An automated training regimen coaches rats to willingly submit themselves to repeated brain imaging.

Single-cell epigenetics p1060

Measuring DNA methylation at specific sites in single cells sheds light on early embryo development.

Methods in Brief

Tools in Brief



The need for transparency and good practices in the qPCR literature pp1063 - 1067

Stephen A Bustin, Vladimir Benes, Jeremy Garson, Jan Hellemans, Jim Huggett, Mikael Kubista, Reinhold Mueller, Tania Nolan, Michael W Pfaffl, Gregory Shipley, Carl T Wittwer, Peter Schjerling, Philip J Day, Mónica Abreu, Begoña Aguado, Jean-François Beaulieu, Anneleen Beckers, Sara Bogaert, John A Browne, Fernando Carrasco-Ramiro, Liesbeth Ceelen, Kate Ciborowski, Pieter Cornillie, Stephanie Coulon, Ann Cuypers, Sara De Brouwer, Leentje De Ceuninck, Jurgen De Craene, Hélène De Naeyer, Ward De Spiegelaere, Kato Deckers, Annelies Dheedene, Kaat Durinck, Margarida Ferreira-Teixeira, Annelies Fieuw, Jack M Gallup, Sandra Gonzalo-Flores, Karen Goossens, Femke Heindryckx, Elizabeth Herring, Hans Hoenicka, Laura Icardi, Rolf Jaggi, Farzad Javad, Michael Karampelias, Frederick Kibenge, Molly Kibenge, Candy Kumps, Irina Lambertz, Tim Lammens, Amelia Markey, Peter Messiaen, Evelien Mets, Sofia Morais, Alberto Mudarra-Rubio, Justine Nakiwala, Hilde Nelis, Pal A Olsvik, Claudina Pérez-Novo, Michelle Plusquin, Tony Remans, Ali Rihani, Paulo Rodrigues-Santos, Pieter Rondou, Rebecca Sanders, Katharina Schmidt-Bleek, Kerstin Skovgaard, Karen Smeets, Laura Tabera, Stefan Toegel, Tim Van Acker, Wim Van den Broeck, Joni Van der Meulen, Mireille Van Gele, Gert Van Peer, Mario Van Poucke, Nadine Van Roy, Sarah Vergult, Joris Wauman, Marina Tshuikina-Wiklander, Erik Willems, Sara Zaccara, Fjoralba Zeka & Jo Vandesompele


Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not.


Technology Feature

Neuroscience waves to the crowd pp1069 - 1074

Vivien Marx


Researchers scale up how to crowdsource the mapping of neural circuits. These projects entice crowds by tapping into their spirit of play.


News and Views

Making connections: using networks to stratify human tumors pp1077 - 1078

Benjamin J Raphael


Network-based stratification (NBS) enables the subtyping of tumors on the basis of their mutational profiles, providing new avenues for cancer research and precision oncology.

See also: Article by Hofree et al.



Brief Communications

IntOGen-mutations identifies cancer drivers across tumor types Open pp1081 - 1082

Abel Gonzalez-Perez, Christian Perez-Llamas, Jordi Deu-Pons, David Tamborero, Michael P Schroeder, Alba Jene-Sanz, Alberto Santos & Nuria Lopez-Bigas


IntOGen-mutations is a discovery tool for cancer researchers to find driver mutations in genes and pathways.

eXtasy: variant prioritization by genomic data fusion pp1083 - 1084

Alejandro Sifrim, Dusan Popovic, Leon-Charles Tranchevent, Amin Ardeshirdavani, Ryo Sakai, Peter Konings, Joris R Vermeesch, Jan Aerts, Bart De Moor & Yves Moreau


By fusing genomic data, the eXtasy tool effectively prioritizes rare human exomic sequence variants as causal disease variants.

Inducible control of gene expression with destabilized Cre pp1085 - 1088

Richard Sando III, Karsten Baumgaertel, Simon Pieraut, Nina Torabi-Rander, Thomas J Wandless, Mark Mayford & Anton Maximov


A system to control gene expression based on a destabilized form of Cre recombinase is reported. Drug-induced stabilization of Cre triggers recombination of 'floxed' alleles in the genome and is here used to genetically modify the activity of neural circuits in the mouse brain.

Predicting functional gene interactions with the hierarchical interaction score pp1089 - 1092

Berend Snijder, Prisca Liberali, Mathieu Frechin, Thomas Stoeger & Lucas Pelkmans


This paper introduces and benchmarks a statistic, the hierarchical interaction score, a statistic for measuring functional interactions between genes from large-scale data, and provides accessible methods for calculating this score.

Accounting for technical noise in single-cell RNA-seq experiments pp1093 - 1095

Philip Brennecke, Simon Anders, Jong Kyoung Kim, Aleksandra A Kołodziejczyk, Xiuwei Zhang, Valentina Proserpio, Bianka Baying, Vladimir Benes, Sarah A Teichmann, John C Marioni & Marcus G Heisler


A statistical method that uses spike-ins to model the dependence of technical noise on transcript abundance in single-cell RNA-seq experiments allows identification of genes wherein observed variability in read counts can be reliably interpreted as a signal of biological variability as opposed to the effect of technical noise.

Smart-seq2 for sensitive full-length transcriptome profiling in single cells pp1096 - 1098

Simone Picelli, Åsa K Björklund, Omid R Faridani, Sven Sagasser, Gösta Winberg & Rickard Sandberg


Smart-seq2 improves yield and length in single cell-derived cDNA libraries and uses off-the-shelf reagents.

Exploiting tertiary structure through local folds for crystallographic phasing pp1099 - 1101

Massimo Sammito, Claudia Millán, Dayté D Rodríguez, Iñaki M de Ilarduya, Kathrin Meindl, Ivan De Marino, Giovanna Petrillo, Rubén M Buey, José M de Pereda, Kornelius Zeth, George M Sheldrick & Isabel Usón


An algorithm and software tool, Borges, utilizes nonspecific tertiary-structure fragment information available in the Protein Data Bank to phase protein X-ray diffraction data.

Improved low-resolution crystallographic refinement with Phenix and Rosetta pp1102 - 1104

Frank DiMaio, Nathaniel Echols, Jeffrey J Headd, Thomas C Terwilliger, Paul D Adams & David Baker


An approach combining the sampling methodology and energy function of Rosetta with the X-ray refinement methodology of Phenix enables improved low-resolution crystallographic refinement.

Genetically encoded calcium indicator illuminates calcium dynamics in primary cilia pp1105 - 1107

Steven Su, Siew Cheng Phua, Robert DeRose, Shuhei Chiba, Keishi Narita, Peter N Kalugin, Toshiaki Katada, Kenji Kontani, Sen Takeda & Takanari Inoue


By targeting calcium indicators to primary cilia, micrometer-long protrusions from the cellular plasma membrane, the authors measure Ca2+ signaling in these sensory organelles.



Network-based stratification of tumor mutations Open pp1108 - 1115

Matan Hofree, John P Shen, Hannah Carter, Andrew Gross & Trey Ideker


This paper reports a strategy for combining somatic mutation profiles of human tumors with gene networks to stratify tumors into biologically and clinically relevant subtypes. The method is applied to ovarian, uterine and lung cancers.

See also: News and Views by Raphael

Orthogonal Cas9 proteins for RNA-guided gene regulation and editing pp1116 - 1121

Kevin M Esvelt, Prashant Mali, Jonathan L Braff, Mark Moosburner, Stephanie J Yaung & George M Church


A set of Cas9 endonucleases orthogonal to the Streptococcus pyogenes enzyme is identified. This will enable simultaneous addressing of multiple RNA-guided activities to different genomic target sites with the CRISPR-Cas9 system.

Instant super-resolution imaging in live cells and embryos via analog image processing pp1122 - 1126

Andrew G York, Panagiotis Chandris, Damian Dalle Nogare, Jeffrey Head, Peter Wawrzusin, Robert S Fischer, Ajay Chitnis & Hari Shroff


An analog implementation of structured illumination using matched microlens and pinhole arrays allows up to 100-Hz 3D two-color imaging with 145-nm lateral and 350-nm axial resolution.

Image-based transcriptomics in thousands of single human cells at single-molecule resolution pp1127 - 1133

Nico Battich, Thomas Stoeger & Lucas Pelkmans


An automated experimental and software pipeline for large-scale FISH enables spatial transcriptomics in thousands of single human cells at single-molecule resolution.



Application Note

Trypsin/Lys-C protease mix for enhanced protein mass spectrometry analysis

Sergei Saveliev, Mark Bratz, Roman Zubarev, Matt Szapacs, Harshavardhan Budamgunta & Marjeta Urh