Opportunities and challenges for biomarker discovery using electronic health record data.

Electronic health records (EHRs) have become increasingly relied upon as a source for biomedical research. One important research application of EHRs is the identification of biomarkers associated with specific patient states, especially within complex conditions. However, using EHRs for biomarker identification can be challenging because the EHR was not designed with research as the primary focus. Despite this challenge, the EHR offers huge potential for biomarker discovery research to transform our understanding of disease etiology and treatment and generate biological insights informing precision medicine initiatives. This review paper provides an in-depth analysis of how EHR data is currently used for phenotyping and identifying molecular biomarkers, current challenges and limitations, and strategies we can take to mitigate challenges going forward.

Exploring human biology with N-of-1 clinical trials.

Studies on humans that exploit contemporary data-intensive, high-throughput 'omic' assay technologies, such as genomics, transcriptomics, proteomics and metabolomics, have unequivocally revealed that humans differ greatly at the molecular level. These differences, which are compounded by each individual's distinct behavioral and environmental exposures, impact individual responses to health interventions such as diet and drugs. Questions about the best way to tailor health interventions to individuals based on their nuanced genomic, physiologic, behavioral, etc. profiles have motivated the current emphasis on 'precision' medicine. This review's purpose is to describe how the design and execution of N-of-1 (or personalized) multivariate clinical trials can advance the field. Such trials focus on individual responses to health interventions from a whole-person perspective, leverage emerging health monitoring technologies, and can be used to address the most relevant questions in the precision medicine era. This includes how to validate biomarkers that may indicate appropriate activity of an intervention as well as how to identify likely beneficial interventions for an individual. We also argue that multivariate N-of-1 and aggregated N-of-1 trials are ideal vehicles for advancing biomedical and translational science in the precision medicine era since the insights gained from them can not only shed light on how to treat or prevent diseases generally, but also provide insight into how to provide real-time care to the very individuals who are seeking attention for their health concerns in the first place.