Volume 20 Issue 9, September 2023

They started their lab mid-COVID. The new principal investigator adventure is a roller-coaster ride with some unexpected surprises.

Nature uses only the longest threads to weave her patterns, so that each small piece of her fabric reveals the organization of the entire tapestry. —Richard Feynman

An expansion microscopy technique called ChromExM offers detailed views into the organization chromatin and associated gene expression machinery in embryos.

Researchers like the gene-editing method called prime editing for its precision and versatility. As they ask the method to do more, many factors shape what happens next.

Multiplexed spatial immunophenotyping has advanced our understanding of tissues in the context of homeostasis and disease. Two studies now provide additional tools to overcome challenges with multiplexed imaging: one procedure amplifies the detection of low-abundance antigens by integrating SABER and IMC technologies, and the other is an X-ray-based method that enables the non-destructive multiplexed detection of antigens in tissues at scalable resolution and speed.

Recently proposed computational approaches explore casual links between chromatin and transcriptional changes that are provided by single-cell multimodal sequencing to bridge the knowledge gap in transcriptional regulatory control.

The conversion of biological molecules into digital signals through sequencing is a complex process that often generates substantial systematic background noise. This noise can obscure important biological insights. However, by precisely identifying and removing this noise, we can bring the true signal into focus and eliminate misleading results from downstream analyses.

Single-cell perturbation screens are routinely conducted to study the effects of different perturbations on cellular state, yet such studies are easily confounded by nuisance sources of variation shared with control cells. We present a deep learning method that isolates perturbation-specific sources of variation, enabling a better understanding of the perturbation’s effects.

We developed, characterized and validated nLight sensors, a new family of genetically encoded green and red fluorescent norepinephrine indicators based on an alpha-1 adrenergic receptor. nLight probes can detect norepinephrine in living animals with superior sensitivity, ligand specificity and temporal resolution as compared with previous tools.

This Perspective introduces the Minimum Information About Disorder Experiments guidelines, which provide a community consensus on the minimum information required to appropriately describe metadata on experimentally and computationally derived structural state(s) of intrinsically disordered proteins or regions.

SABER-IMC combines DNA-based signal amplification by exchange reaction (SABER) with imaging mass cytometry (IMC) to enable simultaneous and highly multiplexed marker detection, even of low-abundance markers not detectable with IMC alone.

Multielement Z-tag X-ray fluorescence (MEZ-XRF) offers a new avenue for nondestructive and highly multiplexed tissue imaging and operates from the nanometer to whole-tissue scale, unlocking new biological observations.

Using a deep generative model, CellBender models and denoises droplet-based single-cell data and improves multiple downstream analyses.

contrastiveVI separates single-cell gene expression variations uniquely related to treatment conditions from those shared with control conditions using a probabilistic latent variable model.

Compared to other sequences, extra-long tandem repeats, such as centromeres and immunoglobulin loci, are more difficult to align. This study presents UniAligner, a computational method for efficiently and accurately aligning extra-long tandem repeats, facilitating analysis of their variation and evolution.

SCENIC+ is a comprehensive toolbox for inferring and analyzing enhancer-driven gene regulatory networks using single-cell multiomic data.

By probabilistic modeling of gene regulation and expression kinetics, Dictys infers dynamic and context-specific gene regulatory networks using single-cell multiomics data.

Gaussian Process Spatial Alignment (GPSA) aligns multiple spatially resolved genomics and histology datasets and improves downstream analysis.

HDRobust is a high-precision tool for homology-directed repair-mediated single-nucleotide editing.

This article describes a time-resolved cryo-plunger that combines a droplet-based microfluidic mixer with a laser-induced generator of microjets that allows rapid reaction initiation and plunge-freezing of cryo-EM grids. A time resolution of 5 ms was achieved using this approach.

Voltage-Seq combines voltage imaging, optogenetics and single-cell RNA-seq for high-throughput analysis of functional and transcriptomic properties of neurons in situ.

FIOLA is a pipeline for processing calcium or voltage imaging data. Its advantages include the fast speed and online processing.

Red and green genetically encoded indicators for norepinephrine have been developed and employed to monitor norepinephrine during locomotion and reward behavior in mice. The strategy used for generating these indicators also produced indicators for other neuromodulators.