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Annual Review of Microbiology Sep 2023Here we review two connected themes in evolutionary microbiology: () the nature of gene repertoire variation within species groups (pangenomes) and () the concept of... (Review)
Review
Here we review two connected themes in evolutionary microbiology: () the nature of gene repertoire variation within species groups (pangenomes) and () the concept of metabolite transporters as accessory proteins capable of providing niche-defining "bolt-on" phenotypes. We discuss the need for improved sampling and understanding of pangenome variation in eukaryotic microbes. We then review the factors that shape the repertoire of accessory genes within pangenomes. As part of this discussion, we outline how gene duplication is a key factor in both eukaryotic pangenome variation and transporter gene family evolution. We go on to outline how, through functional characterization of transporter-encoding genes, in combination with analyses of how transporter genes are gained and lost from accessory genomes, we can reveal much about the niche range, the ecology, and the evolution of virulence of microbes. We advocate for the coordinated systematic study of eukaryotic pangenomes through genome sequencing and the functional analysis of genes found within the accessory gene repertoire.
Topics: Eukaryota; Eukaryotic Cells; Membrane Transport Proteins; Gene Duplication; Phenotype
PubMed: 36944262
DOI: 10.1146/annurev-micro-032421-115538 -
Pharmacological Research Jan 2024Macrophages, as highly phenotypic plastic immune cells, play diverse roles in different pathological conditions. Changing and controlling the phenotypes of macrophages... (Review)
Review
Macrophages, as highly phenotypic plastic immune cells, play diverse roles in different pathological conditions. Changing and controlling the phenotypes of macrophages is considered a novel potential therapeutic intervention. Meanwhile, specific transmembrane proteins anchoring on the surface of the macrophage membrane are relatively conserved, supporting its functional properties, such as inflammatory chemotaxis and tumor targeting. Thus, a series of drug delivery systems related to specific macrophage membrane proteins are commonly used to treat chronic inflammatory diseases. This review summarizes macrophages-based strategies for chronic diseases, discusses the regulation of macrophage phenotypes and their polarization processes, and presents how to design and apply the site-specific targeted drug delivery systems in vivo based on the macrophages and their derived membrane receptors. It aims to provide a better understanding of macrophages in immunoregulation and proposes macrophages-based targeted therapeutic approaches for chronic diseases.
Topics: Humans; Drug Delivery Systems; Phenotype; Macrophages; Neoplasms; Chronic Disease
PubMed: 38043691
DOI: 10.1016/j.phrs.2023.107022 -
BMC Ecology and Evolution Jan 2024Abrupt environmental changes can lead to evolutionary shifts in trait evolution. Identifying these shifts is an important step in understanding the evolutionary history...
Abrupt environmental changes can lead to evolutionary shifts in trait evolution. Identifying these shifts is an important step in understanding the evolutionary history of phenotypes. The detection performances of different methods are influenced by many factors, including different numbers of shifts, shift sizes, where a shift occurs on a tree, and the types of phylogenetic structure. Furthermore, the model assumptions are oversimplified, so are likely to be violated in real data, which could cause the methods to fail. We perform simulations to assess the effect of these factors on the performance of shift detection methods. To make the comparisons more complete, we also propose an ensemble variable selection method (R package ELPASO) and compare it with existing methods (R packages [Formula: see text]1ou and PhylogeneticEM). The performances of methods are highly dependent on the selection criterion. [Formula: see text]1ou+pBIC is usually the most conservative method and it performs well when signal sizes are large. [Formula: see text]1ou+BIC is the least conservative method and it performs well when signal sizes are small. The ensemble method provides more balanced choices between those two methods. Moreover, the performances of all methods are heavily impacted by measurement error, tree reconstruction error and shifts in variance.
Topics: Phylogeny; Phenotype
PubMed: 38245667
DOI: 10.1186/s12862-024-02201-w -
Genetics in Medicine : Official Journal... Sep 2023Congenital hypopituitarism (CH) disorders are phenotypically variable. Variants in multiple genes are associated with these disorders, with variable penetrance and...
PURPOSE
Congenital hypopituitarism (CH) disorders are phenotypically variable. Variants in multiple genes are associated with these disorders, with variable penetrance and inheritance.
METHODS
We screened a large cohort (N = 1765) of patients with or at risk of CH using Sanger sequencing, selected according to phenotype, and conducted next-generation sequencing (NGS) in 51 families within our cohort. We report the clinical, hormonal, and neuroradiological phenotypes of patients with variants in known genes associated with CH.
RESULTS
We identified variants in 178 patients: GH1/GHRHR (51 patients of 414 screened), PROP1 (17 of 253), POU1F1 (15 of 139), SOX2 (13 of 59), GLI2 (7 of 106), LHX3/LHX4 (8 of 110), HESX1 (8 of 724), SOX3 (9 of 354), OTX2 (5 of 59), SHH (2 of 64), and TCF7L1, KAL1, FGFR1, and FGF8 (2 of 585, respectively). NGS identified 26 novel variants in 35 patients (from 24 families). Magnetic resonance imaging showed prevalent hypothalamo-pituitary abnormalities, present in all patients with PROP1, GLI2, SOX3, HESX1, OTX2, LHX3, and LHX4 variants. Normal hypothalamo-pituitary anatomy was reported in 24 of 121, predominantly those with GH1, GHRHR, POU1F1, and SOX2 variants.
CONCLUSION
We identified variants in 10% (178 of 1765) of our CH cohort. NGS has revolutionized variant identification, and careful phenotypic patient characterization has improved our understanding of CH. We have constructed a flow chart to guide genetic analysis in these patients, which will evolve upon novel gene discoveries.
Topics: Humans; Mutation; Hypopituitarism; Transcription Factors; Phenotype; Genes, Homeobox
PubMed: 37165954
DOI: 10.1016/j.gim.2023.100881 -
Nature Human Behaviour May 2024Computational phenotyping has emerged as a powerful tool for characterizing individual variability across a variety of cognitive domains. An individual's computational...
Computational phenotyping has emerged as a powerful tool for characterizing individual variability across a variety of cognitive domains. An individual's computational phenotype is defined as a set of mechanistically interpretable parameters obtained from fitting computational models to behavioural data. However, the interpretation of these parameters hinges critically on their psychometric properties, which are rarely studied. To identify the sources governing the temporal variability of the computational phenotype, we carried out a 12-week longitudinal study using a battery of seven tasks that measure aspects of human learning, memory, perception and decision making. To examine the influence of state effects, each week, participants provided reports tracking their mood, habits and daily activities. We developed a dynamic computational phenotyping framework, which allowed us to tease apart the time-varying effects of practice and internal states such as affective valence and arousal. Our results show that many phenotype dimensions covary with practice and affective factors, indicating that what appears to be unreliability may reflect previously unmeasured structure. These results support a fundamentally dynamic understanding of cognitive variability within an individual.
Topics: Humans; Cognition; Phenotype; Male; Female; Longitudinal Studies; Decision Making; Adult; Young Adult; Learning; Affect; Memory; Individuality
PubMed: 38332340
DOI: 10.1038/s41562-024-01814-x -
Frontiers in Immunology 2024Mucosal-associated invariant T (MAIT) cells are a subpopulation of unconventional T cells widely involved in chronic liver diseases. However, the potential role and...
Mucosal-associated invariant T (MAIT) cells are a subpopulation of unconventional T cells widely involved in chronic liver diseases. However, the potential role and regulating factors of MAIT cells in alveolar echinococcosis (AE), a zoonotic parasitic disease by () larvae chronically parasitizing liver organs, has not yet been studied. Blood samples (n=29) and liver specimens (n=10) from AE patients were enrolled. The frequency, phenotype, and function of MAIT cells in peripheral blood and liver tissues of AE patients were detected by flow cytometry. The morphology and fibrosis of liver tissue were examined by histopathology and immunohistochemistry. The correlation between peripheral MAIT cell frequency and serologic markers was assessed by collecting clinicopathologic characteristics of AE patients. And the effect of stimulation with antigen (Emp) on MAIT cells. In this study, MAIT cells are decreased in peripheral blood and increased in the close-to-lesion liver tissues, especially in areas of fibrosis. Circulating MAIT exhibited activation and exhaustion phenotypes, and intrahepatic MAIT cells showed increased activation phenotypes with increased IFN-γ and IL-17A, and high expression of CXCR5 chemokine receptor. Furthermore, the frequency of circulating MAIT cells was correlated with the size of the lesions and liver function in patients with AE. After excision of the lesion site, circulating MAIT cells returned to normal levels, and the serum cytokines IL-8, IL-12, and IL-18, associated with MAIT cell activation and apoptosis, were altered. Our results demonstrate the status of MAIT cell distribution, functional phenotype, and migration in peripheral blood and tissues of AE patients, highlighting their potential as biomarkers and therapeutic targets.
Topics: Humans; Mucosal-Associated Invariant T Cells; Cytokines; Phenotype; Fibrosis; Echinococcosis
PubMed: 38550591
DOI: 10.3389/fimmu.2024.1343567 -
Arthritis Research & Therapy Sep 2023We investigated sensitivity of the 2020 Revised Comprehensive Diagnostic Criteria (RCD) and the 2019 ACR/EULAR classification criteria across the four identified...
Differential sensitivity of the 2020 revised comprehensive diagnostic criteria and the 2019 ACR/EULAR classification criteria across IgG4-related disease phenotypes: results from a Norwegian cohort.
BACKGROUND
We investigated sensitivity of the 2020 Revised Comprehensive Diagnostic Criteria (RCD) and the 2019 ACR/EULAR classification criteria across the four identified IgG4-related disease (IgG4-RD) phenotypes: "Pancreato-Hepato-Biliary", "Retroperitoneum and Aorta", "Head and Neck-limited" and "Mikulicz' and Systemic" in a well-characterized patient cohort.
METHODS
We included adult patients diagnosed with IgG4-RD after comprehensive clinical assessment at Oslo University Hospital in Norway. We assigned patients to IgG4-RD phenotypes based on pattern of organ involvement and assessed fulfillment of RCD and 2019 ACR/EULAR classification criteria. Differences between phenotype groups were analyzed using one-way ANOVA for continuous variables, and contingency tables for categorical variables.
RESULTS
The study cohort included 79 IgG4-RD patients assigned to the "Pancreato-Hepato-Biliary" (22.8%), Retroperitoneum and Aorta" (22.8%) "Head and Neck-limited" (29.1%), and "Mikulicz' and Systemic" (25.3%) phenotype groups, respectively. While 72/79 (91.1%) patients in total fulfilled the RCD, proportion differed across phenotype groups and was lowest in the "Retroperitoneum and Aorta" group (66.7%, p < 0.001). Among the 57 (72.2%) patients meeting the 2019 ACR/EULAR classification criteria, proportion was again lowest in the "Retroperitoneum and Aorta" group (27.8%, p < 0.001).
CONCLUSION
The results from this study indicate that IgG4-RD patients having the "Retroperitoneum and Aorta" phenotype less often fulfill diagnostic criteria and classification criteria than patients with other IgG4-RD phenotypes. Accordingly, this phenotype is at risk of being systematically selected against in observational studies and randomized clinical trials, with potential implications for patients, caregivers and future definitions of IgG4-RD.
Topics: Humans; Immunoglobulin G4-Related Disease; Norway; Phenotype
PubMed: 37670401
DOI: 10.1186/s13075-023-03155-y -
Annual Review of Biomedical Data Science Aug 2023Autism spectrum disorder (autism) is a neurodevelopmental delay that affects at least 1 in 44 children. Like many neurological disorder phenotypes, the diagnostic... (Review)
Review
Autism spectrum disorder (autism) is a neurodevelopmental delay that affects at least 1 in 44 children. Like many neurological disorder phenotypes, the diagnostic features are observable, can be tracked over time, and can be managed or even eliminated through proper therapy and treatments. However, there are major bottlenecks in the diagnostic, therapeutic, and longitudinal tracking pipelines for autism and related neurodevelopmental delays, creating an opportunity for novel data science solutions to augment and transform existing workflows and provide increased access to services for affected families. Several efforts previously conducted by a multitude of research labs have spawned great progress toward improved digital diagnostics and digital therapies for children with autism. We review the literature on digital health methods for autism behavior quantification and beneficial therapies using data science. We describe both case-control studies and classification systems for digital phenotyping. We then discuss digital diagnostics and therapeutics that integrate machine learning models of autism-related behaviors, including the factors that must be addressed for translational use. Finally, we describe ongoing challenges and potential opportunities for the field of autism data science. Given the heterogeneous nature of autism and the complexities of the relevant behaviors, this review contains insights that are relevant to neurological behavior analysis and digital psychiatry more broadly.
Topics: Humans; Autistic Disorder; Autism Spectrum Disorder; Data Science; Machine Learning; Phenotype
PubMed: 37137169
DOI: 10.1146/annurev-biodatasci-020722-125454 -
Mammalian Genome : Official Journal of... Dec 2023The Mouse Phenome Database continues to serve as a curated repository and analysis suite for measured attributes of members of diverse mouse populations. The repository... (Meta-Analysis)
Meta-Analysis Review
The Mouse Phenome Database continues to serve as a curated repository and analysis suite for measured attributes of members of diverse mouse populations. The repository includes annotation to community standard ontologies and guidelines, a database of allelic states for 657 mouse strains, a collection of protocols, and analysis tools for flexible, interactive, user directed analyses that increasingly integrates data across traits and populations. The database has grown from its initial focus on a standard set of inbred strains to include heterogeneous mouse populations such as the Diversity Outbred and mapping crosses and well as Collaborative Cross, Hybrid Mouse Diversity Panel, and recombinant inbred strains. Most recently the system has expanded to include data from the International Mouse Phenotyping Consortium. Collectively these data are accessible by API and provided with an interactive tool suite that enables users' persistent selection, storage, and operation on collections of measures. The tool suite allows basic analyses, advanced functions with dynamic visualization including multi-population meta-analysis, multivariate outlier detection, trait pattern matching, correlation analyses and other functions. The data resources and analysis suite provide users a flexible environment in which to explore the basis of phenotypic variation in health and disease across the lifespan.
Topics: Mice; Animals; Mice, Inbred Strains; Phenotype; Phenomics
PubMed: 37581698
DOI: 10.1007/s00335-023-10014-3 -
BMC Oral Health Jan 2024Periodontal phenotype is regarded to be one of the key factors influencing the efficacy of restorative therapies in dental practice. The objective of the systematic...
BACKGROUND
Periodontal phenotype is regarded to be one of the key factors influencing the efficacy of restorative therapies in dental practice. The objective of the systematic review was to explore the importance of thin and thick periodontal phenotypes and how they affect the outcome of periodontal and restorative therapies by looking at a number of academic publications from various online databases.
METHODS
Following the PRISMA guidelines (Preferred Reporting Items for Systematic Review standards), relevant data will be searched and retrieved from three significant scientific databases, including PubMed, EBSCO, and Scopus. The articles with full texts that matched the keywords and published in English between 2018 and 2023 were taken into consideration.
RESULTS
The majorities of these articles were based on the type of periodontal phenotype and their impact on periodontal and restorative treatment outcomes were selected. The initial search yielded a total of 530 articles. Only 273 were relevant to the review's objectives, and these were considered for determining eligibility. Only 20 publications were eligible for analysis.
CONCLUSION
Understanding these anatomical aspects of periodontal phenotype is crucial to both periodontology and restorative dentistry. The clinical outcome of restorative, prosthetic, orthodontic, surgical, and periodontal therapies is determined in large part by the periodontal phenotype, which also plays a significant role in clinical failure or success in dental treatments.
TRIAL REGISTRATION
This study protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO) dated 16th June 2023 with the registration ID CRD42023432568.
Topics: Humans; Periodontics; Dental Care; Databases, Factual; Phenotype
PubMed: 38191372
DOI: 10.1186/s12903-023-03777-3