Fundamentals of Ion Mobility-Mass Spectrometry for the Analysis of Biomolecules.

Ion mobility-mass spectrometry (IM-MS) combines complementary size- and mass-selective separations into a single analytical platform. This chapter provides context for both the instrumental arrangements and key application areas that are commonly encountered in bioanalytical settings. New advances in these high-throughput strategies are described with description of complementary informatics tools to effectively utilize these data-intensive measurements. Rapid separations such as these are especially important in systems, synthetic, and chemical biology in which many small molecules are transient and correspond to various biological classes for integrated omics measurements. This chapter highlights the fundamentals of IM-MS and its applications toward biomolecular separations and discusses methods currently being used in the fields of proteomics, lipidomics, and metabolomics.

IMass Time: The Future, in Future!

Joseph John Thomson discovered and proved the existence of electrons through a series of experiments. His work earned him a Nobel Prize in 1906 and initiated the era of mass spectrometry (MS). In the intervening time, other researchers have also been awarded the Nobel Prize for significant advances in MS technology. The development of soft ionization techniques was central to the application of MS to large biological molecules and led to an unprecedented interest in the study of biomolecules such as proteins (proteomics), metabolites (metabolomics), carbohydrates (glycomics), and lipids (lipidomics), allowing a better understanding of the molecular underpinnings of health and disease. The interest in large molecules drove improvements in MS resolution and now the challenge is in data deconvolution, intelligent exploitation of heterogeneous data, and interpretation, all of which can be ameliorated with a proposed IMass technology. We define IMass as a combination of MS and artificial intelligence, with each performing a specific role. IMass will offer advantages such as improving speed, sensitivity, and analyses of large data that are presently not possible with MS alone. In this study, we present an overview of the MS considering historical perspectives and applications, challenges, as well as insightful highlights of IMass.

TRIENNIAL LACTATION SYMPOSIUM/BOLFA:Historical perspectives of lactation biology in the late 20th and early 21st centuries.

The latter half of the 20th century and the early portion of the 21st century will be recognized as the "Golden Age" of lactation biology. This period corresponded with the rise of systemic, metabolomic, molecular, and genomic biology. It includes the discovery of the structure of DNA and ends with the sequencing of the complete genomes of humans and all major domestic animal species including the dairy cow. This included the ability to identify polymorphisms in the nucleic acid sequence, which can be tied to specific differences in cellular, tissue, and animal performance. Before this period, classical work using endocrine ablation and replacement studies identified the mammary gland as an endocrine-dependent organ. In the early 1960s, the development of RIA and radioreceptor assays permitted the study of the relationship between endocrine patterns and mammary function. The ability to measure nucleic acid content of tissues opened the door to study of the factors regulating mammary growth. The development of high-speed centrifugation in the 1960s allowed separation of specific cell organelles and their membranes. The development of transmission and scanning electron microscopy permitted the study of the relationship between structure and function in the mammary secretory cell. The availability of radiolabeled metabolites provided the opportunity to investigate the metabolic pathways and their regulation. The development of concepts regarding the coordination of metabolism to support lactation integrated our understanding of nutrient partitioning and homeostasis. The ability to produce recombinant molecules and organisms permitted enhancement of lactation in farm animal species and the production of milk containing proteins of value to human medicine. These discoveries and others contributed to vastly increased dairy farm productivity in the United States and worldwide. This review will include the discussion of the centers of excellence and scientists who labored in these fields to produce the harvest of knowledge we enjoy today.

Informatics for Metabolomics.

Metabolome profiling of biological systems has the powerful ability to provide the biological understanding of their metabolic functional states responding to the environmental factors or other perturbations. Tons of accumulative metabolomics data have thus been established since pre-metabolomics era. This is directly influenced by the high-throughput analytical techniques, especially mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based techniques. Continuously, the significant numbers of informatics techniques for data processing, statistical analysis, and data mining have been developed. The following tools and databases are advanced for the metabolomics society which provide the useful metabolomics information, e.g., the chemical structures, mass spectrum patterns for peak identification, metabolite profiles, biological functions, dynamic metabolite changes, and biochemical transformations of thousands of small molecules. In this chapter, we aim to introduce overall metabolomics studies from pre- to post-metabolomics era and their impact on society. Directing on post-metabolomics era, we provide a conceptual framework of informatics techniques for metabolomics and show useful examples of techniques, tools, and databases for metabolomics data analysis starting from preprocessing toward functional interpretation. Throughout the framework of informatics techniques for metabolomics provided, it can be further used as a scaffold for translational biomedical research which can thus lead to reveal new metabolite biomarkers, potential metabolic targets, or key metabolic pathways for future disease therapy.

Looking back into the future: 30 years of metabolomics at TNO.

Metabolites have played an essential role in our understanding of life, health, and disease for thousands of years. This domain became much more important after the concept of metabolism was discovered. In the 1950s, mass spectrometry was coupled to chromatography and made the technique more application-oriented and allowed the development of new profiling technologies. Since 1980, TNO has performed system-based metabolic profiling of body fluids, and combined with pattern recognition has led to many discoveries and contributed to the field known as metabolomics and systems biology. This review describes the development of related concepts and applications at TNO in the biomedical, pharmaceutical, nutritional, and microbiological fields, and provides an outlook for the future.

Metabolic systems biology.

The first full genome sequences were established in the mid-1990s. Shortly thereafter, genome-scale metabolic network reconstructions appeared. Since that time, we have witnessed an exponential growth in their number and uses. Here I discuss, from a personal point of view, four topics: (1) the placement of metabolic systems biology in the context of broader scientific developments, (2) its foundational concepts, (3) some of its current uses, and (4) some of the expected future developments in the field.

Metabolomics, a novel tool for studies of nutrition, metabolism and lipid dysfunction.

AIMS: In this review metabolomics is introduced in historic perspective, with key platforms and bioinformatics methodologies described. An overview is provided covering recent applications of metabolomics and lipidomics in the context of human physiology, lipid metabolism and nutrition. DATA SYNTHESIS: Global coverage of human metabolome requires application of multiple analytical platforms. The choice of a particular targeted or non-targeted analytical strategy depends on the hypothesis tested, state-of-the-art in the field, as well as on sample availability. Human metabolome has been shown to be sensitive to age, gut microbial composition, and lifestyle. Several studies have shown that, given the appropriate experimental design, subtle effects of interventions such as change of diet or weight loss can be detected by metabolomics and studied in the context of human physiology and health status. CONCLUSION: Metabolome provides a sensitive intermediate phenotype linking the genotype, gut microbial composition and personal health status. Innovative experimental designs combined with novel computational tools for handling metabolomics data offer new opportunities for early disease detection as well as for characterization of dietary and therapeutic interventions in the context of human physiology.