Towards Structural Systems Pharmacology to Study Complex Diseases and Personalized Medicine

Genome-Wide Association Studies (GWAS), whole genome sequencing, and high-throughput omics techniques have generated vast amounts of genotypic and molecular phenotypic data. However, these data have not yet been fully explored to improve the effectiveness and efficiency of drug discovery, which continues along a one-drug-one-target-one-disease paradigm. As a partial consequence, both the cost to launch a new drug and the attrition rate are increasing. Systems pharmacology and pharmacogenomics are emerging to exploit the available data and potentially reverse this trend, but, as we argue here, more is needed. To understand the impact of genetic, epigenetic, and environmental factors on drug action, we must study the structural energetics and dynamics of molecular interactions in the context of the whole human genome and interactome. Such an approach requires an integrative modeling framework for drug action that leverages advances in data-driven statistical modeling and mechanism-based multiscale modeling and transforms heterogeneous data from GWAS, high-throughput sequencing, structural genomics, functional genomics, and chemical genomics into unified knowledge. This is not a small task, but, as reviewed here, progress is being made towards the final goal of personalized medicines for the treatment of complex diseases

The organizational environment with its measures, antecedents, and consequences: A review and research agenda

The organizational environment is a focal element of multifaceted managerial decisions. Consequently, research has shown a long lasting and still growing interest in investigating the organizational environment and understanding its impact on a firm. Because it is widely assumed that the business environment will become more dynamic, changes in the organizational environment have drawn the particular attention of many scholars. While the extant research has established valuable knowledge, its fragmentation due to differing definitions and contradictory findings calls for a broad review to establish a foundation for future research. By analyzing 279 studies that have investigated different aspects of the organizational environment between 1958 and mid-2017, we contribute to various research streams that involve this environmental factor. We use a comprehensive research framework to categorize and review the previous work. In particular, we distinguish between studies that define or measure the organizational environment, as well as studies that investigate antecedents, outcomes, and moderating effects of the organizational environments. Among those categories, we discuss our findings, before subsequently synthesizing existing works and deriving an agenda for future research