Comment

The field of single-cell RNA sequencing (scRNA-seq) has been paired with genomics, epigenomics, spatial omics, proteomics and imaging to achieve multimodal measurements of individual cellular phenotypes and genotypes. In its purest form, single-cell multimodal omics involves the simultaneous detection of multiple traits in the same cell. More broadly, multimodal omics also encompasses comparative pairing and computational integration of measurements made across multiple distinct cells to reconstruct phenotypes. Here I highlight some of the biological insights gained from multimodal studies and discuss the challenges and opportunities in this emerging field.

Advances in single-cell genomics technologies have enabled investigation of the gene regulation programs of multicellular organisms at unprecedented resolution and scale. Development of single-cell multimodal omics tools is another major step toward understanding the inner workings of biological systems.

The growth of advanced, custom microscopy has outpaced commercialization, with biologists unable to benefit from these developments. We propose a complementary model for access based on shareable, traveling and configurable microscopes, with potential benefits for biologists, developers and the community.

Single-particle techniques offer an unprecedented opportunity to understand the role of structural variability in biological function. They also call into question the meaning of ‘a structure’ and its relevance to function.

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.

We propose a network of national imaging centers that provide collaborative, interdisciplinary spaces needed for the development, application, and teaching of advanced biological imaging techniques. Our proposal is based on recommendations from a National Science Foundation (NSF)-sponsored workshop on realizing the promise of innovations in imaging and computation for biological discovery.

The PLUMED consortium unifies developers and contributors to PLUMED, an open-source library for enhanced-sampling, free-energy calculations and the analysis of molecular dynamics simulations. Here, we outline our efforts to promote transparency and reproducibility by disseminating protocols for enhanced-sampling molecular simulations.

Microbiomes play critical roles in ecosystems and human health, yet in most cases scientists lack standardized and reproducible model microbial communities. The development of fabricated microbial ecosystems, which we term EcoFABs, will provide such model systems for microbiome studies.

Developments in imaging tools are making it possible to record activity from both large neuronal populations and subcellular components in freely moving animals. Although these developments are enabling relationships between brain activity and complex behaviors to be explored, many challenges need to be overcome before the potential of the freely moving animal can be fully utilized.

The development of systems combining rapid volumetric imaging with three-dimensional tracking has enabled the measurement of brain-wide dynamics in freely behaving animals such as worms, flies, and fish. These advances provide an exciting opportunity to understand the organization of neural circuits in the context of voluntary and natural behaviors. In this Comment, we highlight recent progress in this burgeoning area of research.

One major challenge in neuroscience is to uncover how defined neural circuits in the brain encode, store, modify, and retrieve information. Meeting this challenge comprehensively requires tools capable of recording and manipulating the activity of intact neural networks in naturally behaving animals. Head-mounted miniature microscopes are emerging as a key tool to address this challenge. Here we discuss recent work leading to the miniaturization of neural imaging tools, the current state of the art in this field, and the importance and necessity of open-source options. We finish with a discussion on what the future may hold for miniature microscopy.

Inbred mice are preferred over outbred mice because it is assumed that they display less trait variability. We compared coefficients of variation and did not find evidence of greater trait stability in inbred mice. We conclude that contrary to conventional wisdom, outbred mice might be better subjects for most biomedical research.

Public data archives are the backbone of modern biological research. Biomolecular archives are well established, but bioimaging resources lag behind them. The technology required for imaging archives is now available, thus enabling the creation of the first public bioimage datasets. We present the rationale for the construction of bioimage archives and their associated databases to underpin the next revolution in bioinformatics discovery.