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Progress in Biophysics and Molecular... Mar 2023In the predominately gene-centered view of 20th century biology, the relationship between genotype and phenotype was essentially a relationship between cause and effect,... (Review)
Review
In the predominately gene-centered view of 20th century biology, the relationship between genotype and phenotype was essentially a relationship between cause and effect, between a plan and a product. Abandoning the idea of genes as inherited instructions or blueprints for phenotypes raises the question of how to best account for observed phenotypic stability and variability within and across generations of a population. We argue that the processes responsible for phenotypic stability and the processes responsible for phenotypic variability are one and the same, namely, the dynamics of development. This argument proposes that stability of phenotypic form is found not because of the transmission of genotypes, genetic programs, or the transfer of internal blueprints, but because similar internal and external conditions-collectively conceptualized as resources of development-can be reliably reconstituted in each generation. Variability of phenotypic form, which is an indispensable feature of any evolving system, relies on these same resources, but because the internal and external conditions of development are not reconstituted identically in succeeding generations, these conditions-and the phenotypes to which they give rise-will always be characterized by at least some variability.
Topics: Biological Evolution; Genetic Determinism; Phenotype; Genotype
PubMed: 36682588
DOI: 10.1016/j.pbiomolbio.2023.01.003 -
Seminars in Cell & Developmental Biology Sep 2019Processes in collective migration span many length and time scales. In this review, we focus on length scales ranging from tens of microns (single cells) to a few... (Review)
Review
Processes in collective migration span many length and time scales. In this review, we focus on length scales ranging from tens of microns (single cells) to a few millimeters (cell clusters) and the motion of these cells and cell groups on time scales of minutes to hours. We focus on epithelial cell sheets and metrics of motion developed to measure migration phenotypes in this system. Comparisons between cell motion and fluid flows, facilitated by the popular image analysis technique particle image velocimetry, yield metrics that can be used to study migration across a range of length and time scales. Measuring collective cell migration across these scales provides a complex, quantitative phenotype useful for migration models, in particular those that compare and contrast collective cell migration to movement of particles near a transition to jamming. Contrasting the motion of epithelial cells and the jamming transition illustrates aspects of collective motion that can be attributed to the jammed character of cell clusters, and highlights aspects of collective behavior that likely involve active motility and cell-cell guidance. The application of multiple migration metrics, which span multiple scales of the system, thus allows us to link cell-scale signals and mechanics to collective behavior.
Topics: Cell Movement; Humans; Phenotype; Time Factors
PubMed: 31429407
DOI: 10.1016/j.semcdb.2018.10.010 -
American Journal of Medical Genetics.... Apr 2023The diagnosis of rare Mendelian disorders usually relies upon the interpretation of prose and is complicated by a lack of objective, reproducible phenotypic data. To... (Review)
Review
The diagnosis of rare Mendelian disorders usually relies upon the interpretation of prose and is complicated by a lack of objective, reproducible phenotypic data. To address this limitation, we developed a next generation phenotyping workflow to phenotypically characterize developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities (DEGCAGS). We identified 15 people affected with DEGCAGS, including one novel patient identified at our hospital and 14 patients previously reported in the literature. Human Phenotype Ontology (HPO) terms were extracted from the patient chart and literature review. The HPO terms were sorted by count according to HPO hierarchy of terms. Phenotypes that cosegregate were identified utilizing a co-occurrence matrix. A quantitative narrative illustrated by violin plots was created for our patient from phenotypic data per each day of hospital admission. A total of 252 unique HPO terms were extracted from the patient record and literature review. The highest count of systemically sorted and unsorted terms and the most commonly co-occurring terms were described. A violin plot of phenotype occurrences demonstrated a progression of phenotypes over time. NGP offers a quantitative approach to phenotyping to generate phenotypic data in an objective and reproducible manner akin to NGS.
Topics: Humans; Electronic Health Records; Narration; Phenotype; Rare Diseases
PubMed: 36607994
DOI: 10.1002/ajmg.a.63111 -
Autoimmunity Reviews Oct 2022Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are two types of primary large vessel vasculitis (LVV). LVV is an intractable, rare disease with a high relapse... (Review)
Review
Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are two types of primary large vessel vasculitis (LVV). LVV is an intractable, rare disease with a high relapse rate. Disease progression in asymptomatic patients is an important issue in the clinical management of LVV. Useful biomarkers associated with clinical phenotypes, disease activity, and prognosis may be present in peripheral blood. In this review, we focused on peripheral leukocyte counts, surface markers, functions, and gene expression in LVV patients. In particular, we explored longitudinal changes in circulating immune cell phenotypes during the active phase of the disease and during treatment. The numbers and phenotypes of leukocytes in the peripheral blood were different between LVV and healthy controls, GCA and TAK, LVV in active versus treatment phases, and LVV in treatment responders versus non-responders. Therefore, biomarkers obtained from peripheral blood immune cells may be useful for longitudinal monitoring of disease activity in LVV.
Topics: Biomarkers; Giant Cell Arteritis; Humans; Phenotype; Prognosis; Takayasu Arteritis
PubMed: 35926769
DOI: 10.1016/j.autrev.2022.103160 -
Advanced high-throughput plant phenotyping techniques for genome-wide association studies: A review.Journal of Advanced Research Jan 2022Linking phenotypes and genotypes to identify genetic architectures that regulate important traits is crucial for plant breeding and the development of plant genomics. In... (Review)
Review
Linking phenotypes and genotypes to identify genetic architectures that regulate important traits is crucial for plant breeding and the development of plant genomics. In recent years, genome-wide association studies (GWASs) have been applied extensively to interpret relationships between genes and traits. Successful GWAS application requires comprehensive genomic and phenotypic data from large populations. Although multiple high-throughput DNA sequencing approaches are available for the generation of genomics data, the capacity to generate high-quality phenotypic data is lagging far behind. Traditional methods for plant phenotyping mostly rely on manual measurements, which are laborious, inaccurate, and time-consuming, greatly impairing the acquisition of phenotypic data from large populations. In contrast, high-throughput phenotyping has unique advantages, facilitating rapid, non-destructive, and high-throughput detection, and, in turn, addressing the shortcomings of traditional methods. This review summarizes the current status with regard to the integration of high-throughput phenotyping and GWAS in plants, in addition to discussing the inherent challenges and future prospects. High-throughput phenotyping, which facilitates non-contact and dynamic measurements, has the potential to offer high-quality trait data for GWAS and, in turn, to enhance the unraveling of genetic structures of complex plant traits. In conclusion, high-throughput phenotyping integration with GWAS could facilitate the revealing of coding information in plant genomes.
Topics: Genome, Plant; Genome-Wide Association Study; Genotype; Phenotype; Plant Breeding
PubMed: 35003802
DOI: 10.1016/j.jare.2021.05.002 -
Journal of Sleep Research Dec 2023Insomnia nosology has significantly evolved since the Diagnostic and Statistical Manual (DSM)-III-R first distinguished between 'primary' and 'secondary' insomnia. Prior... (Review)
Review
Insomnia nosology has significantly evolved since the Diagnostic and Statistical Manual (DSM)-III-R first distinguished between 'primary' and 'secondary' insomnia. Prior International Classification of Sleep Disorders (ICSD) nosology 'split' diagnostic phenotypes to address insomnia's heterogeneity and the DSM nosology 'lumped' them into primary insomnia, while both systems assumed causality for insomnia secondary to health conditions. In this systematic review, we discuss the historical phenotypes in prior insomnia nosology, present findings for currently proposed insomnia phenotypes based on more robust approaches, and critically appraise the most relevant ones. Electronic databases PsychINFO, PubMED, Web of Science, and references of eligible articles, were accessed to find diagnostic manuals, literature on insomnia phenotypes, including systematic reviews or meta-analysis, and assessments of the reliability or validity of insomnia diagnoses, identifying 184 articles. The data show that previous insomnia diagnoses lacked reliability and validity, leading current DSM-5-TR and ICSD-3 nosology to 'lump' phenotypes into a single diagnosis comorbid with health conditions. However, at least two new, robust insomnia phenotyping approaches were identified. One approach is multidimensional-multimethod and provides evidence for self-reported insomnia with objective short versus normal sleep duration linked to clinically relevant outcomes, while the other is multidimensional and provides evidence for two to five clusters (phenotypes) based on self-reported trait, state, and/or life-history data. Some approaches still need replication to better support whether their findings identify true phenotypes or simply different patterns of symptomatology. Regardless, these phenotyping efforts aim at improving insomnia nosology both as a classification system and as a mechanism to guide treatment.
Topics: Humans; International Classification of Diseases; Phenotype; Reproducibility of Results; Self Report; Sleep Initiation and Maintenance Disorders
PubMed: 37122153
DOI: 10.1111/jsr.13910 -
Dental Clinics of North America Apr 2021Older adults have multiple morbidities that can impact oral, systemic, and psychological health. Although each disorder requires consideration from the provider before... (Review)
Review
Older adults have multiple morbidities that can impact oral, systemic, and psychological health. Although each disorder requires consideration from the provider before treatment, by assessing the common phenotypic presentations of older adults, we can better understand, select, and coordinate treatment modifications that would need to be considered and implemented for dental care.
Topics: Aged; Humans; Oral Health; Phenotype
PubMed: 33641754
DOI: 10.1016/j.cden.2020.11.005 -
AMIA ... Annual Symposium Proceedings.... 2022Acute kidney injury (AKI) is a life-threatening and heterogeneous syndrome. Timely and etiology-based personalized treatment is crucial. AKI sub-phenotyping can lead to...
Acute kidney injury (AKI) is a life-threatening and heterogeneous syndrome. Timely and etiology-based personalized treatment is crucial. AKI sub-phenotyping can lead to better understanding of the pathophysiology of AKI and help developing more targeted intervention. Current dimensionality reduction and similarity-based clustering for AKI sub-phenotyping suffer from limited interpretability and specificity. To address these limitations, we propose a pattern mining approach with multiobjective evolutionary algorithm (MOEA) for AKI sub-phenotyping. AKI sub-phenotypes are presented as explicit rules, so no post-hoc explanation is needed. Also, our method can search feature subspace efficiently for minor and highly specific sub-phenotypes. We aimed to discover sub-phenotypes for AKI patients against non-AKI patients (AKI vs non-AKI) and moderate-to-severe AKI patients against mild AKI patients (AKI-2/3 vs AKI-1). We identified 174(178) significant sub-phenotypes with average confidence of 0.33(0.33). Our method can assign patients to a sub-phenotype with higher confidence than k-means clustering, with average improvement of 0.20(0.23).
Topics: Humans; Phenotype; Acute Kidney Injury
PubMed: 37128400
DOI: No ID Found -
Bioinformatics (Oxford, England) May 2024Whole-exome and genome sequencing have become common tools in diagnosing patients with rare diseases. Despite their success, this approach leaves many patients...
MOTIVATION
Whole-exome and genome sequencing have become common tools in diagnosing patients with rare diseases. Despite their success, this approach leaves many patients undiagnosed. A common argument is that more disease variants still await discovery, or the novelty of disease phenotypes results from a combination of variants in multiple disease-related genes. Interpreting the phenotypic consequences of genomic variants relies on information about gene functions, gene expression, physiology, and other genomic features. Phenotype-based methods to identify variants involved in genetic diseases combine molecular features with prior knowledge about the phenotypic consequences of altering gene functions. While phenotype-based methods have been successfully applied to prioritizing variants, such methods are based on known gene-disease or gene-phenotype associations as training data and are applicable to genes that have phenotypes associated, thereby limiting their scope. In addition, phenotypes are not assigned uniformly by different clinicians, and phenotype-based methods need to account for this variability.
RESULTS
We developed an Embedding-based Phenotype Variant Predictor (EmbedPVP), a computational method to prioritize variants involved in genetic diseases by combining genomic information and clinical phenotypes. EmbedPVP leverages a large amount of background knowledge from human and model organisms about molecular mechanisms through which abnormal phenotypes may arise. Specifically, EmbedPVP incorporates phenotypes linked to genes, functions of gene products, and the anatomical site of gene expression, and systematically relates them to their phenotypic effects through neuro-symbolic, knowledge-enhanced machine learning. We demonstrate EmbedPVP's efficacy on a large set of synthetic genomes and genomes matched with clinical information.
AVAILABILITY AND IMPLEMENTATION
EmbedPVP and all evaluation experiments are freely available at https://github.com/bio-ontology-research-group/EmbedPVP.
Topics: Humans; Genomics; Phenotype; Genetic Variation; Computational Biology; Machine Learning
PubMed: 38696757
DOI: 10.1093/bioinformatics/btae301 -
Neuroscience and Biobehavioral Reviews Jun 2022This paper aims to review the limitations of the current classification of insomnia of early childhood and propose a new conceptual model allowing a better understanding... (Review)
Review
This paper aims to review the limitations of the current classification of insomnia of early childhood and propose a new conceptual model allowing a better understanding of its pathophysiology. Our hypothesis is that chronic insomnia of childhood has different phenotypical expressions, associated to different pathophysiological mechanisms. Based on a long-lasting experience in evaluating a very large number of children with specific insomnia symptoms (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings) and on published data, we hypothesize that different phenotypes of insomnia might exist with different therapeutic implications. We describe three phenotypes of insomnia in early childhood: a) insomnia with motor restlessness; b) insomnia characterized without difficulties in falling asleep but with long-lasting early morning awakenings; c) insomnia with multiple night awakenings and falling asleep difficulty. This type of categorization might have important implications for treatment, based on the different hypothetical neurotransmitter dysfunctions. The early identification of a phenotype of insomnia might guide to specific behavioral and/or pharmacological interventions with the aim to prevent chronic insomnia.
Topics: Child, Preschool; Humans; Phenotype; Psychomotor Agitation; Sleep Initiation and Maintenance Disorders
PubMed: 35398115
DOI: 10.1016/j.neubiorev.2022.104653