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KEY POINTS

KEY POINTS

  1. Researchers and physicians are now examining human health and disease in the context of the human genome, epigenome, transcriptome, proteome, and microbiome.

  2. In critical illness, disease processes are multifaceted, involving numerous interactions between genes and gene products rather than a single locus.

  3. Network medicine focuses on integrating various omic disciplines to create networks that explain healthy and diseased states.

  4. Network model analysis of ARDS has revealed redundancy in protein connectivity, with several proteins involved in multiple pathways.

  5. More basic research needs to be completed, followed by integration of genomic, epigenomic, transcriptomic, proteomic, microbiomic, and other omic data to create more network models of critical illness.

But nature did not deem it her business to make the discovery of her laws easy for us.

-Albert Einstein (1911)

Within the human body there exists an incredible complexity, making the practice of medicine extremely challenging. No two individuals manifest illness identically. In critical care medicine, where illness strains human physiology to the brink of collapse, this becomes even more apparent. With critical illness accounting for nearly 39% of total hospital costs, now more than ever there is a demand to understand the multifaceted pathology that contributes to individual critical illness.1

For centuries, illness has been studied on a macrolevel with gross anatomy being the epicenter of medicine. However, with the completion of the Human Genome Project (2003), a new paradigm of medicine that focuses on molecular interactions is evolving. Researchers and physicians are now examining human health and disease in the context of the human genome, epigenome, transcriptome, proteome, and microbiome.2,3,4,5,6 Furthermore, these “omes” are being integrated to create new network models of physiology and pathology (Figure 88–1).

Figure 88–1

A new paradigm of medicine is developing, which examines illness through the interactions of the human genome, epigenome, transcriptome, proteome, microbiome, and other developing omes.

Since the inception of the omic era, multiple disease states have been examined including Alzheimer’s disease, cancer, and obesity. However, the application of omics and network medicine to critical illness remains vastly unexplored. The intensive care unit is an uncharted frontier. As omics continues to rapidly expand, the molecular derangements of critical illness will become increasingly apparent. Such insight will evolve the practice of critical care medicine—allowing intensivists to augment their understanding of disease, and to more efficiently diagnose and treat the individual with critical illness. (See the “Glossary and Abbreviations” section for key terms.)

FROM MENDEL TO THE HUMAN GENOME PROJECT

For ages mankind has been fascinated by human variability (Table 88–1). Scientists have extensively hypothesized about the origins and variability of man. One of the earliest recognized publications addressing this query came from Dr. William Harvey, an English ...

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