Commentary

Driven by the importance of spatial and physical factors in cellular processes and the size and complexity of modern image data, computational analysis of biological imagery has become a vital emerging sub-discipline of bioinformatics and computer vision.

We discuss the advantages and challenges of the open-source strategy in biological image analysis and argue that its full impact will not be realized without better support and recognition of software engineers' contributions to the biological sciences and more support of this development model from funders and institutions.

Bioimaging software developed in a research setting often is not widely used by the scientific community. We suggest that, to maximize both the public's and researchers' investments, usability should be a more highly valued goal. We describe specific characteristics of usability toward which bioimaging software projects should aim.

Informatics has driven mass spectrometry–based protein analysis to create large-scale methods for proteomics. As software algorithms have developed, comparisons between algorithms are inevitable. We outline steps for fair and objective comparisons that will make true innovations apparent.

Zinc-finger nuclease dimers are more difficult to engineer than single DNA-binding domains, but the development of new methods could help.

Engineered nucleases have advanced the field of gene therapy with the promise of targeted genome modification as a treatment for human diseases. Here we discuss why engineered nucleases are an exciting research tool for gene editing and consider their applications to a range of biological questions.

Bioorthogonal chemistry allows a wide variety of biomolecules to be specifically labeled and probed in living cells and whole organisms. Here we discuss the history of bioorthogonal reactions and some of the most interesting and important advances in the field.

A diverse array of small molecule–based fluorescent probes is available for many different types of biological experiments. Here we examine the history of these probes and discuss some of the most interesting applications.

In recent years, single-molecule force spectroscopy techniques have been used to study how inter- and intramolecular interactions control the assembly and functional state of biomolecular machinery in vitro. Here we discuss the problems and challenges that need to be addressed to bring these technologies into living cells and to learn how cellular machinery is controlled in vivo.

The low cost of short-read sequencing has motivated the development of de novo assemblies from only short-read data; impressively, assemblies for large mammalian genomes are now available. However, this is still a developing field, and these de novo assemblies have many artifacts, as do all de novo assemblies.

Optogenetics is routinely used to activate and inactivate genetically defined neuronal populations in vivo. A second optogenetic revolution will occur when spatially distributed and sparse neural assemblies can be precisely manipulated in behaving animals.

Rhodopsins from microalgae and eubacteria are powerful tools for manipulating the function of neurons and other cells, but these tools still have limitations. We discuss engineering approaches that can help advance optogenetics.

Optogenetics is a technology that allows targeted, fast control of precisely defined events in biological systems as complex as freely moving mammals. By delivering optical control at the speed (millisecond-scale) and with the precision (cell type–specific) required for biological processing, optogenetic approaches have opened new landscapes for the study of biology, both in health and disease.

Optogenetic modules offer cell biologists unprecedented new ways to poke and prod cells. The combination of these precision perturbative tools with observational tools, such as fluorescent proteins, may dramatically accelerate our ability to understand the inner workings of the cell.

Mass spectrometry has evolved and matured to a level where it is able to assess the complexity of the human proteome. We discuss some of the expected challenges ahead and promising strategies for success.

Methods and tools for visualizing biological data have improved considerably over the last decades, but they are still inadequate for some high-throughput data sets. For most users, a key challenge is to benefit from the deluge of data without being overwhelmed by it. This challenge is still largely unfulfilled and will require the development of truly integrated and highly useable tools.

The field of induced pluripotent stem cells (iPSCs) will be subject to a wide range of laws and research ethics policies, many of which exist as a result of the controversies associated with research on human embryonic stem cells. Understanding this potentially complex regulatory environment will help iPSC research move forward and will inform future policy.

The discovery that it is possible to render somatic cells pluripotent by the exogenous expression of a set of transcription factors provides an experimental model for studying the molecular nature of cellular identity.

iPS cell technology makes patient- and disease-specific human cells widely available. While technical challenges still remain, the use of these tools will greatly expand our understanding of human disease.