Volume 16 Issue 9, September 2019

Staying mobile and building a Toy-Story-related way to stitch terabyte-sized images in microscopy.

“Everything we see hides another thing, we always want to see what is hidden by what we see” — Rene Magritte

Whole-body energy expenditure is the summed metabolic activities of tissues and, to remove the influence of body size, ratios of energy expenditure to body mass are often applied but can generate spurious differences. In 2011, a group of experts proposed adoption of ANCOVA for the analysis of metabolic rate but, seven years later, analyses based on ratios remain the most frequent. We discuss some of the barriers to adopting better analytical procedures.

Single-cell sequencing of Hydra results in a resource for studying differentiation trajectories, regeneration and nervous system development.

A DNA origami rotor amplifies and tracks DNA movements during biochemical reactions, uncovering action mechanisms of genome-processing enzymes.

Tagging and sequencing RNAs that are in close spatial proximity in the nucleus shows how the transcriptome is partitioned.

An improved method to detect coevolving residues at protein interfaces allows proteome-wide screening of PPIs.

The development of biologically compatible microdisk lasers enables massively multiplexed cell tracking.

As single-cell proteomics emerges, perhaps labs can avoid the need to infer protein levels from mRNA abundances.

Single objective light-sheet fluorescence microscopes combine the convenience of conventional sample mounting with sensitive subcellular and super-resolution imaging of cells and tissues.

Best practices for carrying out and reporting ensemble FRET measurements in the cuvette and in cells.

This Perspective summarizes advances in stimulated Raman spectroscopy (SRS) instruments and probes, and highlights biological discoveries made with these technologies.

In this DREAM challenge, 75 methods for the identification of disease-relevant modules from molecular networks are compared and validated with GWAS data. The authors provide practical guidelines for users and establish benchmarks for network analysis.

Single-molecule oblique-plane microscopy (obSTORM) enables deep volumetric super-resolution imaging in a light-sheet microscopy platform that is convenient for standard tissues and small intact animals.

By embedding DNA sequences that are known to bind transcription factors in vitro together with labels for the TFs in a high-dimensional space, the machine learning approach BindSpace distinguishes between the binding preferences of even closely related TFs.

Pepper, an RNA aptamer that prevents degradation of degron-tagged fluorescent proteins, enables fully genetically encoded fluorescence imaging of mRNA in living cells.

An optimized F-box protein–degron pair enables efficient auxin-mediated protein degradation with minimal basal degradation in human cells and is suitable for transmembrane, cytoplasmic and nuclear proteins.

BigStitcher enables fast and accurate alignment and reconstruction of terabyte-sized imaging datasets of cleared and expanded samples.

SAVER-X trains a deep neural network for transfer learning that improves the quality of scRNA-seq data using prior information learnt from existing public studies.

FLAM-seq implements a cDNA library preparation followed by single-molecule sequencing, for determining full-length mRNA molecules, including poly(A) tails.

A single transcript encoding Cas12a and an array of CRISPR RNAs enables multiplexed genome engineering, from multiple knockouts to transcriptional activation or repression to orthogonal transcriptional control and editing in the same sample.

A massively parallel biophysical approach, Hotspot Thermal Profiling, analyzes the effects of phosphorylation on protein stability across the proteome in live cells.

O-glycopeptides and O-glycan structures can be identified and quantified on a proteome-wide scale with Glyco-DIA, a data-independent-acquisition mass spectrometry-based method.

Emap2sec uses a deep convolutional neural network to assign protein secondary structures in intermediate-resolution (5–10 Å) cryo-EM maps.

Decorrelation analysis offers an improved method for assessing image resolution that works on a single image and is insensitive to common image artifacts. The method can be applied generally to any type of microscopy images.

Adapting a t-MALDI-2 ion source to an Orbitrap mass analyzer enables mass spectrometry imaging of cells and tissues with (sub)cellular resolution.