Table of contents


Special Feature

Method of the Year 2017

We've chosen organoids as Method of the Year 2017, for their immense potential as tools to study human biology in health and disease. A News Feature gives a flavor of the exciting applications of these 3D constructs, and a Primer provides a short overview for newcomers to the field. Two expert Commentaries consider these tools from different angles: how cutting-edge imaging is synergizing with organoid culture to deepen our view into many biological systems, and how pluripotent stem cell-derived constructs can be used to model the human brain. As in the past, we've also chosen eight 'methods to watch' for the future.



Special Feature: Method of the Year 2017

Method of the Year 2017: Organoids p1


The ability to prod stem cells into three-dimensional tissue models makes for a powerful way to study human biology. But these exciting tools are still works in progress.


This Month

Kasper Lage p3

Vivien Marx


Scoring genes in light of their 'friends', and a naval approach to science.

Points of significance: Machine learning: supervised methods pp5 - 6

Danilo Bzdok, Martin Krzywinski & Naomi Altman


Supervised learning algorithms extract general principles from observed examples guided by a specific prediction objective.



A profusion of confusion in NGS methods naming pp7 - 8

James Hadfield & Jacques Retief


motifStack for the analysis of transcription factor binding site evolution pp8 - 9

Jianhong Ou, Scot A Wolfe, Michael H Brodsky & Lihua Julie Zhu



Research Highlights

It takes two to trans-Tango p11

Trans-Tango allows trans-synaptic mapping of presynaptic and postsynaptic partners in Drosophila.

Reflecting on light sheets pp12 - 13

Reflective coverslips can improve spatiotemporal resolution and collection efficiency in diSPIM light-sheet fluorescence microscopy.

Sequencing DNA, no mistake pp12 - 13

Building redundancy into fluorogenic sequencing makes for error-free DNA sequence reads.

High-resolution mapping of R loops p14

Two novel techniques refine genome-wide mapping of R loops.

Depleting endogenous proteins p17

Using antibodies to target specific proteins for rapid degradation is a versatile approach for studying the function of endogenous proteins.

Methods in Brief

Tools in Brief


News Feature

Special Feature: Method of the Year 2017

Organoids: the body builders pp19 - 22

Michael Eisenstein




Special Feature: Method of the Year 2017

Organoids p23

Natalie de Souza


A brief overview of stem cell-derived organoids: how they are made and what the challenges are.



Special Feature: Method of the Year 2017

Imaging organoids: a bright future ahead pp24 - 26

Anne C Rios & Hans Clevers



Methods to Watch

Special Feature: Method of the Year 2017

Spatial transcriptomics p30

Tal Nawy


It will soon be commonplace to localize gene expression in tissues.

Special Feature: Method of the Year 2017

Structure via super-resolution p30

Natalie de Souza


Fluorescence nanoscopy is extending its reach into structural biology.

Special Feature: Method of the Year 2017

Towards a dynamic 3D genome p31

Nicole Rusk


Sequencing and imaging bring unique aspects to genome architecture.

Special Feature: Method of the Year 2017

Transformative electrophysiology p31

Nina Vogt


Increases in throughput push electrophysiology into a new era.

Special Feature: Method of the Year 2017

Mass spectrometry imaging takes off p32

Allison Doerr


Recent advances in mass spectrometry imaging enable label-free molecular mapping in single cells and in 3D.

Special Feature: Method of the Year 2017

Tracing cellular descent p32

Tal Nawy


Sophisticated barcoding approaches are transforming cell lineaging.

Special Feature: Method of the Year 2017

The new XFELs p33

Allison Doerr


New X-ray free-electron (XFEL) facilities will broaden access to this technology, facilitate methods development, and push boundaries in structural biology.

Special Feature: Method of the Year 2017

Machine learning in neuroscience p33

Nina Vogt


In the era of big data, neuroscience can profit from deep-learning approaches.


Technology Feature

Chemical biology: fats as research subjects pp35 - 38

Vivien Marx


Fats add structure, they signal, they interact. In the lab, lipids are tough to work with but worth the challenge.



Multicolor quantitative confocal imaging cytometry pp39 - 46

Daniel L Coutu, Konstantinos D Kokkaliaris, Leo Kunz & Timm Schroeder


This resource paper describes the steps involved in carrying out quantitative multicolour imaging in tissue. It is applied to cleared mouse bone and plots the spatial distribution of specific cell populations within the marrow.

Systematic characterization of maturation time of fluorescent proteins in living cells pp47 - 51

Enrique Balleza, J Mark Kim & Philippe Cluzel


This work characterizes the maturation kinetics of 50 cyan to far-red fluorescent proteins and provides evidence that proteins that mature faster than their brighter but slower counterparts are more useful for quantitative evaluation of fast processes.


Brief Communications

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics pp53 - 56

Zijuan Lai, Hiroshi Tsugawa, Gert Wohlgemuth, Sajjan Mehta, Matthew Mueller, Yuxuan Zheng, Atsushi Ogiwara, John Meissen, Megan Showalter, Kohei Takeuchi, Tobias Kind, Peter Beal, Masanori Arita & Oliver Fiehn


An integrated cheminformatics workflow aids the functional and structural annotation of unknown metabolites found across multiple biological systems.

Programmable full-adder computations in communicating three-dimensional cell cultures pp57 - 60

David Ausländer, Simon Ausländer, Xavier Pierrat, Leon Hellmann, Leila Rachid & Martin Fussenegger


Designer cells executing rationally assembled genetic programs that can process input signals with programmable logic are combined in a 3D cell culture that performs three-input, two-output full-adder computations.



NetSig: network-based discovery from cancer genomes pp61 - 66

Heiko Horn, Michael S Lawrence, Candace R Chouinard, Yashaswi Shrestha, Jessica Xin Hu, Elizabeth Worstell, Emily Shea, Nina Ilic, Eejung Kim, Atanas Kamburov, Alireza Kashani, William C Hahn, Joshua D Campbell, Jesse S Boehm, Gad Getz & Kasper Lage


NetSig is a network-based statistic that identifies cancer driver genes with high accuracy and can be combined with gene-based statistical tests; results are validated with a large-scale in vivo tumorigenesis assay.

PDB-wide identification of biological assemblies from conserved quaternary structure geometry pp67 - 72

Sucharita Dey, David W Ritchie & Emmanuel D Levy


Monomeric and homo-oligomeric protein quaternary structure states are predicted on a PDB-wide scale using a method that approaches the accuracy of manual annotation.

A permanent window for the murine lung enables high-resolution imaging of cancer metastasis pp73 - 80

David Entenberg, Sonia Voiculescu, Peng Guo, Lucia Borriello, Yarong Wang, George S Karagiannis, Joan Jones, Francis Baccay, Maja Oktay & John Condeelis


The window for high-resolution imaging of the lung (WHRIL) enables longitudinal imaging of the same region of murine lung tissue over a period of weeks, and this enables the visualization of spontaneous cancer metastasis from the earliest stages.

An improved MS2 system for accurate reporting of the mRNA life cycle pp81 - 89

Evelina Tutucci, Maria Vera, Jeetayu Biswas, Jennifer Garcia, Roy Parker & Robert H Singer


An improved MS2-tagging system for live-cell RNA imaging allows faithful monitoring of the mRNA life cycle, overcoming degradation artifacts associated with previous versions and having implications regarding mRNA regulation in yeast.