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Journal of Clinical Immunology Oct 2022The International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) reports here the 2022 updated phenotypic...
The International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) reports here the 2022 updated phenotypic classification, which accompanies and complements the most-recent genotypic classification. This phenotypic classification is aimed for clinicians at the bedside and focuses on clinical features and laboratory phenotypes of specific IEI. In this classification, 485 IEI underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity and auto-inflammation are described, including 55 novel monogenic defects and 1 autoimmune phenocopy. Therefore, all 485 diseases of the genetic classification are presented in this paper in the form of colored tables with essential clinical or immunological phenotype entries.
Topics: Humans; Immunologic Deficiency Syndromes; Phenotype; Genotype; Hypersensitivity; Neoplasms
PubMed: 36198931
DOI: 10.1007/s10875-022-01352-z -
Pulmonology 2020Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and multisystemic disease with progressive increasing morbidity and mortality. COPD is now widely... (Review)
Review
Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and multisystemic disease with progressive increasing morbidity and mortality. COPD is now widely accepted as a heterogeneous condition with multiple phenotypes and endotypes. This review will discuss the old and new concepts for the different types of COPD phenotypes, as well as the inclusion of them in current guidelines. Phenotypical approach to COPD is having huge impact on everyday practice and changed nonpharmacological and pharmacological management of COPD in last decade. However, phenotypical approach is small step to precision medicine in COPD management in the absence of big, specific and well-designed COPD trials with exact identification of phenotypes for more personalization of the treatment of COPD.
Topics: Humans; Phenotype; Practice Guidelines as Topic; Precision Medicine; Pulmonary Disease, Chronic Obstructive
PubMed: 31740261
DOI: 10.1016/j.pulmoe.2019.10.006 -
Circulation Research Apr 2018Precision medicine is an integrative approach to cardiovascular disease prevention and treatment that considers an individual's genetics, lifestyle, and exposures as... (Review)
Review
Precision medicine is an integrative approach to cardiovascular disease prevention and treatment that considers an individual's genetics, lifestyle, and exposures as determinants of their cardiovascular health and disease phenotypes. This focus overcomes the limitations of reductionism in medicine, which presumes that all patients with the same signs of disease share a common pathophenotype and, therefore, should be treated similarly. Precision medicine incorporates standard clinical and health record data with advanced panomics (ie, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics) for deep phenotyping. These phenotypic data can then be analyzed within the framework of molecular interaction (interactome) networks to uncover previously unrecognized disease phenotypes and relationships between diseases, and to select pharmacotherapeutics or identify potential protein-drug or drug-drug interactions. In this review, we discuss the current spectrum of cardiovascular health and disease, population averages and the response of extreme phenotypes to interventions, and population-based versus high-risk treatment strategies as a pretext to understanding a precision medicine approach to cardiovascular disease prevention and therapeutic interventions. We also consider the search for resilience and Mendelian disease genes and argue against the theory of a single causal gene/gene product as a mediator of the cardiovascular disease phenotype, as well as an Erlichian magic bullet to solve cardiovascular disease. Finally, we detail the importance of deep phenotyping and interactome networks and the use of this information for rational polypharmacy. These topics highlight the urgent need for precise phenotyping to advance precision medicine as a strategy to improve cardiovascular health and prevent disease.
Topics: Cardiovascular Agents; Cardiovascular Diseases; Computational Biology; Demography; Drug Discovery; Forecasting; Gene-Environment Interaction; Genetic Association Studies; Genetic Diseases, Inborn; Genetic Variation; Humans; Mutation; Pharmacogenetics; Phenotype; Precision Medicine
PubMed: 29700074
DOI: 10.1161/CIRCRESAHA.117.310782 -
Sleep Medicine Reviews Oct 2017Obstructive sleep apnea (OSA) is a complex and heterogeneous disorder and the apnea hypopnea index alone can not capture the diverse spectrum of the condition. Enhanced... (Review)
Review
Obstructive sleep apnea (OSA) is a complex and heterogeneous disorder and the apnea hypopnea index alone can not capture the diverse spectrum of the condition. Enhanced phenotyping can improve prognostication, patient selection for clinical trials, understanding of mechanisms, and personalized treatments. In OSA, multiple condition characteristics have been termed "phenotypes." To help classify patients into relevant prognostic and therapeutic categories, an OSA phenotype can be operationally defined as: "A category of patients with OSA distinguished from others by a single or combination of disease features, in relation to clinically meaningful attributes (symptoms, response to therapy, health outcomes, quality of life)." We review approaches to clinical phenotyping in OSA, citing examples of increasing analytic complexity. Although clinical feature based OSA phenotypes with significant prognostic and treatment implications have been identified (e.g., excessive daytime sleepiness OSA), many current categorizations lack association with meaningful outcomes. Recent work focused on pathophysiologic risk factors for OSA (e.g., arousal threshold, craniofacial morphology, chemoreflex sensitivity) appears to capture heterogeneity in OSA, but requires clinical validation. Lastly, we discuss the use of machine learning as a promising phenotyping strategy that can integrate multiple types of data (genomic, molecular, cellular, clinical) to identify unique, meaningful OSA phenotypes.
Topics: Humans; Phenotype; Sleep Apnea, Obstructive; Sleep, REM
PubMed: 27815038
DOI: 10.1016/j.smrv.2016.10.002 -
Handbook of Clinical Neurology 2018Essential tremor (ET) is one of the most common neurologic disorders, and genetic factors are thought to contribute significantly to disease etiology. There has been a... (Review)
Review
Essential tremor (ET) is one of the most common neurologic disorders, and genetic factors are thought to contribute significantly to disease etiology. There has been a relative lack of progress in understanding the genetic etiology of ET. This could reflect a number of factors, including the presence of substantial phenotypic and genotypic heterogeneity. Thus, a meticulous approach to phenotyping is important for genetic research. A lack of standardized phenotyping across studies and patient centers likely has contributed to the relative lack of success of genomewide association studies in ET. To dissect the genetic architecture of ET, whole-genome sequencing will likely be of value. This will allow specific hypotheses about the mode of inheritance and genetic architecture to be tested. A number of approaches still remain unexplored in ET genetics, including the contribution of copy number variants, uncommon moderate-effect alleles, rare variant large-effect alleles (including Mendelian and complex/polygenic modes of inheritance), de novo and gonadal mosaicism, epigenetic changes, and noncoding variation.
Topics: Essential Tremor; Gene-Environment Interaction; Genetic Predisposition to Disease; Genotype; Humans; Phenotype
PubMed: 29325613
DOI: 10.1016/B978-0-444-63233-3.00015-4 -
Plant Biotechnology Journal Jul 2020Genotyping-by-sequencing has enabled approaches for genomic selection to improve yield, stress resistance and nutritional value. More and more resource studies are... (Review)
Review
Genotyping-by-sequencing has enabled approaches for genomic selection to improve yield, stress resistance and nutritional value. More and more resource studies are emerging providing 1000 and more genotypes and millions of SNPs for one species covering a hitherto inaccessible intraspecific genetic variation. The larger the databases are growing, the better statistical approaches for genomic selection will be available. However, there are clear limitations on the statistical but also on the biological part. Intraspecific genetic variation is able to explain a high proportion of the phenotypes, but a large part of phenotypic plasticity also stems from environmentally driven transcriptional, post-transcriptional, translational, post-translational, epigenetic and metabolic regulation. Moreover, regulation of the same gene can have different phenotypic outputs in different environments. Consequently, to explain and understand environment-dependent phenotypic plasticity based on the available genotype variation we have to integrate the analysis of further molecular levels reflecting the complete information flow from the gene to metabolism to phenotype. Interestingly, metabolomics platforms are already more cost-effective than NGS platforms and are decisive for the prediction of nutritional value or stress resistance. Here, we propose three fundamental pillars for future breeding strategies in the framework of Green Systems Biology: (i) combining genome selection with environment-dependent PANOMICS analysis and deep learning to improve prediction accuracy for marker-dependent trait performance; (ii) PANOMICS resolution at subtissue, cellular and subcellular level provides information about fundamental functions of selected markers; (iii) combining PANOMICS with genome editing and speed breeding tools to accelerate and enhance large-scale functional validation of trait-specific precision breeding.
Topics: Breeding; Genome-Wide Association Study; Genomics; Genotype; Phenotype; Polymorphism, Single Nucleotide
PubMed: 32163658
DOI: 10.1111/pbi.13372 -
Trends in Ecology & Evolution Jan 2020Genetically identical individuals can be phenotypically variable, even in constant environmental conditions. The ubiquity of this phenomenon, known as 'intra-genotypic... (Review)
Review
Genetically identical individuals can be phenotypically variable, even in constant environmental conditions. The ubiquity of this phenomenon, known as 'intra-genotypic variability', is increasingly evident and the relevant mechanistic underpinnings are beginning to be understood. In parallel, theory has delineated a number of formal expectations for contexts in which such a feature would be adaptive. Here, we review empirical evidence across biological systems and theoretical expectations, including nonlinear averaging and bet hedging. We synthesize existing results to illustrate the dependence of selection outcomes both on trait characteristics, features of environmental variability, and species' demographic context. We conclude by discussing ways to bridge the gap between empirical evidence of intra-genotypic variability, studies demonstrating its genetic component, and evidence that it is adaptive.
Topics: Biological Evolution; Genotype; Humans; Phenotype; Selection, Genetic
PubMed: 31519463
DOI: 10.1016/j.tree.2019.08.005 -
Current Topics in Developmental Biology 2021Genetic assimilation and genetic accommodation are mechanisms by which novel phenotypes are produced and become established in a population. Novel characters may be... (Review)
Review
Genetic assimilation and genetic accommodation are mechanisms by which novel phenotypes are produced and become established in a population. Novel characters may be fixed and canalized so they are insensitive to environmental variation, or can be plastic and adaptively responsive to environmental variation. In this review we explore the various theories that have been proposed to explain the developmental origin and evolution of novel phenotypes and the mechanisms by which canalization and phenotypic plasticity evolve. These theories and models range from conceptual to mathematical and have taken different views of how genes and environment contribute to the development and evolution of the properties of phenotypes. We will argue that a deeper and more nuanced understanding of genetic accommodation requires a recognition that phenotypes are not static entities but are dynamic system properties with no fixed deterministic relationship between genotype and phenotype. We suggest a mechanistic systems-view of development that allows one to incorporate both genes and environment in a common model, and that enables both quantitative analysis and visualization of the evolution of canalization and phenotypic plasticity.
Topics: Adaptation, Physiological; Animals; Biological Evolution; Drosophila; Epigenesis, Genetic; Gene-Environment Interaction; Genetic Techniques; Models, Genetic; Mutation; Phenotype; Plants; Signal Transduction
PubMed: 33602492
DOI: 10.1016/bs.ctdb.2020.11.006 -
Current Opinion in Chemical Biology Dec 2021A cell's phenotype is the culmination of several cellular processes through a complex network of molecular interactions that ultimately result in a unique morphological... (Review)
Review
A cell's phenotype is the culmination of several cellular processes through a complex network of molecular interactions that ultimately result in a unique morphological signature. Visual cell phenotyping is the characterization and quantification of these observable cellular traits in images. Recently, cellular phenotyping has undergone a massive overhaul in terms of scale, resolution, and throughput, which is attributable to advances across electronic, optical, and chemical technologies for imaging cells. Coupled with the rapid acceleration of deep learning-based computational tools, these advances have opened up new avenues for innovation across a wide variety of high-throughput cell biology applications. Here, we review applications wherein deep learning is powering the recognition, profiling, and prediction of visual phenotypes to answer important biological questions. As the complexity and scale of imaging assays increase, deep learning offers computational solutions to elucidate the details of previously unexplored cellular phenotypes.
Topics: Deep Learning; Diagnostic Imaging; Phenotype
PubMed: 34023800
DOI: 10.1016/j.cbpa.2021.04.001 -
Ophthalmic Plastic and Reconstructive... 2018To describe a new classification system of thyroid eye disease (TED) based on the phenotypic features (clinical and radiologic) of the disease. (Review)
Review
PURPOSE
To describe a new classification system of thyroid eye disease (TED) based on the phenotypic features (clinical and radiologic) of the disease.
METHODS
Clinical features, photographic, and orbital imaging of TED patients were considered in relation to their natural history and treatment response in the experience of the author. Phenotypically distinct categories of patients were identified and described.
RESULTS
Six phenotypes of TED are observed: 1) congestive (active inflammatory), 2) "white eye" expansion, 3) "hydraulic" apex, 4) "white eye" apex, 5) cicatricial active, and 6) cicatricial passive.
CONCLUSIONS
The observable characteristics of TED are determined by the underlying pathophysiology of the disease. TED is heterogeneous in its underlying pathogenesis, clinical manifestations, and response to medical and surgical treatment modalities. Several previous categorizations of the clinical appearance of TED exist, but they are dichotomous and underrepresent the heterogeneity of the disease. The authors present clinical and radiologic features of 6 different classes or phenotypes of TED and their response to different treatments.
Topics: Diagnostic Imaging; Disease Management; Graves Ophthalmopathy; Humans; Orbit; Phenotype
PubMed: 29905636
DOI: 10.1097/IOP.0000000000001147