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We have not yet reached a point at which routine sequencing of large numbers of whole eukaryotic genomes is feasible, and so it is often necessary to select genomic regions of interest and to enrich these regions before sequencing. There are several enrichment approaches, each with unique advantages and disadvantages. Here we describe our experiences with the leading target-enrichment technologies, the optimizations that we have performed and typical results that can be obtained using each. We also provide detailed protocols for each technology so that end users can find the best compromise between sensitivity, specificity and uniformity for their particular project.

The practice of clinical cardiology employs many imaging techniques for diagnosis, risk stratification and therapeutic monitoring. These imaging modalities largely provide anatomical or structural information, and only indirectly reflect underlying molecular events. Molecular imaging techniques report on entities or processes that can be defined at the molecular, as opposed to the anatomical, level. For example, molecular imaging can reveal the expression or activity of a specific protein, the fate or localization of a biomolecule, or the activity of a biological pathway. This Review highlights key processes and molecular targets that are currently being investigated experimentally by molecular imaging probes in vivo. Collectively, these targets have an important role in the development of atherosclerosis and acute plaque rupture, as well as in myocardial disease. Molecular imaging technology is now progressing towards clinical application in humans and has the potential to guide diagnosis, risk assessment and treatment response. Imaging-based surrogate end points could speed the development of new drugs, particularly those with novel mechanisms of action. More broadly, by noninvasively reporting on molecular processes in vivo, molecular imaging can reveal how specific proteins or pathways function in their native context, thus contributing to a systems-level understanding of cardiovascular disease biology.

Between 2004 and 2008, the US National Institutes of Health Molecular Libraries and Imaging initiative pilot phase funded 10 high-throughput screening centers, resulting in the deposition of 691 assays into PubChem and the nomination of 64 chemical probes. We crowdsourced the Molecular Libraries and Imaging initiative output to 11 experts, who expressed medium or high levels of confidence in 48 of these 64 probes.