Global chemical analysis of biology by mass spectrometry

Mass spectrometry instruments measure the mass to charge ratio of ions, from which we infer the molecular structures. They are key tools for investigating the incredibly diverse chemistry that is associated with biological systems. Typically, when one thinks about the chemistry of biology, one thinks of biochemical pathways, structural lipids or carbohydrates. However, numerous additional chemistries are part of various biological systems. These include molecules that originate from diet, water treatment, personal care, medications, pollutants and environmental exposures including plastics, clothes and furniture. These principles apply not only to people but to all of biology, from the worms at the bottom of the ocean, to the bacteria in our belly buttons and to the birds that fly over Mount Everest. In the past decade, our capacity to inventory the chemistry of biological systems using mass spectrometry at a global level has been revolutionized. In this Review, we discuss the informatics and hardware tools that are available for small-molecule analysis and provide an overview of the tools that could transform how we study the chemistry of biological systems; perhaps in the future this will be as easy as taking a photograph with a smartphone. An untargeted mass spectrometry analysis of a biological sample will detect both biological molecules and compounds that are derived from, for example, diet and the environment. This Review examines the design of such experiments, how to process and interpret the vast amount of data that are produced, and how far we are from being able to use mass spectrometry to inventory the world around us.