Science for the Next Century: Deep Phenotyping

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

Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective

A vast majority of the pathophysiological and metabolic processes in humans are temporally controlled by a master circadian clock located centrally in the hypothalamic suprachiasmatic nucleus of the brain, as well as by specialized peripheral oscillators located in other body tissues. This circadian clock system generates a rhythmical diurnal transcriptional-translational cycle in clock genes and protein expression and activities regulating numerous downstream target genes. Clock genes as key regulators of physiological function and dysfunction of the circadian clock have been linked to various diseases and multiple morbidities. Emerging omics technologies permits largescale multi-dimensional investigations of the molecular landscape of a given disease and the comprehensive characterization of its underlying cellular components (e.g., proteins, genes, lipids, metabolites), their mechanism of actions, functional networks and regulatory systems. Ultimately, they can be used to better understand disease and interpatient heterogeneity, individual profile, identify personalized targetable key molecules and pathways, discover novel biomarkers and genetic alterations, which collectively can allow for a better patient stratification into clinically relevant subgroups to improve disease prediction and prevention, early diagnostic, clinical outcomes, therapeutic benefits, patient's quality of life and survival. The use of “omics” technologies has allowed for recent breakthroughs in several scientific domains, including in the field of circadian clock biology. Although studies have explored the role of clock genes using circadiOmics (which integrates circadian omics, such as genomics, transcriptomics, proteomics and metabolomics) in human disease, no such studies have investigated the implications of circadian disruption in oral, head and neck pathologies using multi-omics approaches and linking the omics data to patient-specific circadian profiles. There is a burgeoning body of evidence that circadian clock controls the development and homeostasis of oral and maxillofacial structures, such as salivary glands, teeth and oral epithelium. Hence, in the current era of precision medicine and dentistry and patient-centered health care, it is becoming evident that a multi-omics approach is needed to improve our understanding of the role of circadian clock-controlled key players in the regulation of head and neck pathologies. This review discusses current knowledge on the role of the circadian clock and the contribution of omics-based approaches toward a novel precision health era for diagnosing and treating head and neck pathologies, with an emphasis on oral, head and neck cancer and Sjögren's syndrome

Gut health : Predictive biomarkers for preventive medicine and development of functional foods

There is an urgent need to develop and validate a series of biomarkers, which accurately measure and inform on how the human gut microbiota can affect human health. The human gut hosts a complex community of micro-organisms, with unique features in each individual. The functional role of this gut microbiota in health and disease is increasingly evident, but poorly understood. Comprehension of this ecosystem implies a significant challenge in the elucidation of interactions between all of its components, but promises a paradigm shift in preventive nutrition and medicine. Omics technologies for the first time offer tools of sufficient subtlety to tackle this challenge. However, these techniques must be allied with traditional skills of the microbial physiologist, which are in danger of being lost. Targeting these efforts at the identification of biomarkers associated with gut health will require access to a biobank from a pan-European or worldwide observation study, which would include samples taken with appropriate frequency from healthy individuals of different ages. This offers a pragmatic opportunity for a unique food and pharmaceutical industry collaboration

Functional microorganisms in Baijiu Daqu: Research progress and fortification strategy for application

Daqu is a saccharifying and fermenting starter in the production of Chinese Baijiu; its quality directly affects the quality of Baijiu. The production of Daqu is highly environment-dependent, and after long-term natural domestication, it is rich in a wide variety of microorganisms with a stable composition, which provide complex and diverse enzymes and flavor (precursor) substances and microbiota for Jiupei (Fermented grains) fermentation. However, inoculation with a relatively stable microbial community can lead to a certain upper limit or deficiencies of the physicochemical properties (e.g., saccharification capacity, esterification capacity) of the Daqu and affect the functional expression and aroma formation of the Daqu. Targeted improvement of this problem can be proposed by selecting functional microorganisms to fortify the production of Daqu. This review introduced the isolation, screening, identification and functional characteristics of culture-dependent functional microorganisms in Baijiu-brewing, the core functional microbiota community of Daqu, and the related research progress of functional microorganisms fortified Daqu, and summarized the fortifying strategies of functional microorganisms, aiming to further deepen the application of functional microorganisms fortification in Daqu fermentation and provide ideas for the flavor regulation and quality control of Baijiu

Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia

ORAL MICROBIOME CHANGES ASSOCIATED WITH FIXED DENTAL PROSTHODONTIC RESTORATION

The oral microbiome is a relatively unexplored component of oral health and disease. Common oral diseases, including dental caries and periodontitis, are now best understood as dysbiotic shifts of the oral microbial ecology. Prosthodontics is a cornerstone of clinical dentistry, serving to promote oral health through dental rehabilitation. However, it remains unknown if and to what degree prosthodontic treatment confers changes in the oral microbiome. In this observational clinical study, we studied the effects of fixed dental prosthodontic restorative treatment on the oral microbiome composition. Prosthodontic patients’ salivary samples were collected during their treatment course. Microbiome analyses relied upon whole genome sequencing (WGS) shotgun. Reads were aligned, mapped and analyzed to obtain measures relative abundance and diversity, as well as group and time differences. Results to-date have provided novel insights into oral microbiome changes during prosthodontic treatment that may characterize global transitions of clinical oral disease states to health.Master of Scienc

Systems Biology in ELIXIR: modelling in the spotlight

info:eu-repo/semantics/publishedVersio

Advances in diagnostic tools for respiratory tract infections : from tuberculosis to COVID-19 - changing paradigms?

Respiratory tract infections (RTIs) are one of the most common reasons for seeking healthcare, but are amongst the most challenging diseases in terms of clinical decision-making. Proper and timely diagnosis is critical in order to optimise management and prevent further emergence of antimicrobial resistance by misuse or overuse of antibiotics. Diagnostic tools for RTIs include those involving syndromic and aetiological diagnosis: from clinical and radiological features to laboratory methods targeting both pathogen detection and host biomarkers, as well as their combinations in terms of clinical algorithms. They also include tools for predicting severity and monitoring treatment response. Unprecedented milestones have been achieved in the context of the COVID-19 pandemic, involving the most recent applications of diagnostic technologies both at genotypic and phenotypic level, which have changed paradigms in infectious respiratory diseases in terms of why, how and where diagnostics are performed. The aim of this review is to discuss advances in diagnostic tools that impact clinical decision-making, surveillance and follow-up of RTIs and tuberculosis. If properly harnessed, recent advances in diagnostic technologies, including omics and digital transformation, emerge as an unprecedented opportunity to tackle ongoing and future epidemics while handling antimicrobial resistance from a One Health perspective. Unprecedented advances have been achieved by improving and applying the latest technologies to key aspects such as epidemiology, contact tracing and diagnostics of respiratory tract infections that need to be properly addressed for global improvement

Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives