The Nature Methods editorial team gets together each month to pick their favorite methods papers for the Research Highlights and In Brief section. We aim to provide for our readers a balanced selection across the different fields that Nature Methods covers. Below are exciting papers that we unfortunately couldn't highlight in our April issue.

Almagro Armenteros et al. SignalP 5.0 improves signal peptide predictions using deep neural networks

SignalP 5.0 is a deep neural network-based method for predicting signal peptides across all domains of life, with improved prediction performance over previous tools.

Fottner et al. Site-specific ubiquitinylation and SUMOylation using genetic-code expansion and sortase

A combination of genetic code expansion, Staudinger reduction, and sortase-mediated transpeptidation enables inducible ubiquitylation of proteins for functional studies with temporal control.

Li et al. An automated platform for the enzyme-mediated assembly of complex oligosaccharides

A broad range of complex carbohydrates can be made by enzyme-mediated synthesis using an automated catch-and-release platform.

Almeida et al. A new genomic blueprint of the human gut microbiota

More than 90,000 metagenome-assembled genomes from human gut microbiomes were reconstructed, revealing close to 2,000 uncultured bacterial species, in addition to culturable bacteria.

Metsky et al. Capturing sequence diversity in metagenomes with comprehensive and scalable probe design

CATCH is a computational tool for designing oligonucleotide probe sets to improve nucleic acid capture when analyzing diverse microbial taxa. Application of the tool preserves sample diversity in metagenomics sequencing.

Pliss et al. Cycles of protein condensation and discharge in nuclear organelles studied by fluorescence lifetime imaging

Fluorescence lifetime imaging (FLIM) can be applied to study concentration-dependent biocondensation in living cells. Here, cyclic changes in protein concentration within major nuclear organelles and heterochromatin domains could be observed.

Ngo et al. Microcolony Size Distribution Assay Enables High-Throughput Cell Survival Quantitation

The MicroColonyChip facilitates rapid and high-throughput colony forming assays and is applied here to assess radiosensitivity and chemosensitivity.

Wang et al. Solid immersion microscopy images cells under cryogenic conditions with 12 nm resolution

A low-cost super-hemispherical solid immersion lens (superSIL) enables straightforward multicolor, high-resolution localization microscopy at cryogenic conditions.

Kol et al. Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides

Clickable, azobenzene-containing ceramides, caCers, are used for optical control of sphingolipid production in cells.

Jun et al. A “Clickable” Photoconvertible Small Fluorescent Molecule as a Minimalist Probe for Tracking Individual Biomolecule Complexes

CPX is a small photoconvertible probe that can be "clicked" to biological molecules via an azide-alkyne cycloaddition. It can be used to track molecules, complexes and even compartments.

Yang et al. Light sheet microscopy with acoustic sample confinement

A contactless acoustic gradient force trap for sample confinement can help overcome the restrictions of sample immobilisation and mounting in light sheet microscopy.

Tabor et al. Brain-wide cellular resolution imaging of Cre transgenic zebrafish lines for functional circuit-mapping

To facilitate connectivity studies in the zebrafish brain, a resource of more than 50 Cre lines for intersectional mapping have been created, and expression patterns are available at the Zebrafish Brain Browser.

Cabré et al. Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation

Efficient photoswitches for isomerization under two-photon conditions are developed and applied to regulate light-gated glutamate receptors in hippocampal slices and in C. elegans.

Liu et al. A Photoactivatable Botulinum Neurotoxin for Inducible Control of Neurotransmission

A split botulinum neurotoxin has been rendered photoactivatable with the help of the CRY2-CIBN photodimerization tool. The light-inducible tool has been used to inhibit neurotransmission in brain slices as well as in C. elegans.

We hope that you enjoy this selection of methods!