Science for the Next Century: Deep Phenotyping

Abstract

Our ability to unravel the mysteries of human health and disease have changed dramatically over the past 2 decades. Decoding health and disease has been facilitated by the recent availability of high-throughput genomics and multi-omics analyses and the companion tools of advanced informatics and computational science. Understanding of the human genome and its influence on phenotype continues to advance through genotyping large populations and using “light phenotyping” approaches in combination with smaller subsets of the population being evaluated using “deep phenotyping” approaches. Using our capability to integrate and jointly analyze genomic data with other multi-omic data, the knowledge of genotype-phenotype relationships and associated genetic pathways and functions is being advanced. Understanding genotype-phenotype relationships that discriminate human health from disease is speculated to facilitate predictive, precision health care and change modes of health care delivery. The American Association for Dental Research Fall Focused Symposium assembled experts to discuss how studies of genotype-phenotype relationships are illuminating the pathophysiology of craniofacial diseases and developmental biology. Although the breadth of the topic did not allow all areas of dental, oral, and craniofacial research to be addressed (e.g., cancer), the importance and power of integrating genomic, phenomic, and other -omic data are illustrated using a variety of examples. The 8 Fall Focused talks presented different methodological approaches for ascertaining study populations and evaluating population variance and phenotyping approaches. These advances are reviewed in this summary.

Network-Based Methods for Approaching Human Pathologies from a Phenotypic Point of View

“…To conclude, it is clear that the ongoing revolution in the generation of biological data, improvements in computational techniques for data analysis, particularly network analysis, and the ever-increasing recognition of the importance of deep phenotyping of patients [ 91 ], are providing us with a wealth of potential for better understanding disease and eventually finding better treatments.…”

Translating Science into Improved Health for All

“…Our understanding of healthy and diseased states for individuals and communities has the potential for further improvement through the convergence of high-throughput “omic” technologies with innovations in data science, computational biology, and bioengineering (Wright and Herzberg 2021). For example, investments that the NIH and other entities have made in the microbiome, genomics, and other “omics” continue to emerge with direct benefits to oral health and validation of the connection between oral and systemic health.…”

Plasma infrared fingerprinting with machine learning enables single-measurement multi-phenotype health screening

“… 1 , 2 As physiological phenotypes often manifest in the molecular profiles of systemic biofluids (e.g., blood), gateways to quantitatively profile their compositions are invaluable for detecting and characterizing changing health states. 3 , 4 …”