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Karimi, K.

Publications and source records attributed to Karimi, K..

3 recordsLinked to original sources

The Xenopus Phenotype Ontology: bridging model organism phenotype data to human health and development.

BackgroundOntologies of precisely defined, controlled vocabularies are essential to curate the results of biological experiments such that the data are machine searchable, can be computationally analyzed, and are interoperable across the biomedical research continuum. There is also an increasing need for methods to interrelate phenotypic data easily and accurately from experiments in animal models with human development and disease. ResultsHere we present the Xenopus Phenotype Ontology (XPO) to annotate phenotypic data from experiments in Xenopus, one of the major vertebrate model organisms used to study gene function in development and disease. The XPO implements design patterns from the Unified Phenotype Ontology (uPheno), and the principles outlined by the Open Biological and Biomedical Ontologies (OBO Foundry) to maximize interoperability with other species and facilitate ongoing ontology management. Constructed in Web Ontology Language (OWL) the XPO combines the existing uPheno library of ontology design patterns with additional terms from the Xenopus Anatomy Ontology (XAO), the Phenotype and Trait Ontology (PATO) and the Gene Ontology (GO). The integration of these different ontologies into the XPO enables rich phenotypic curation, whilst the uPheno bridging axioms allows phenotypic data from Xenopus experiments to be related to phenotype data from other model organisms and human disease. Moreover, the simple post-composed uPheno design patterns facilitate ongoing XPO development as the generation of new terms and classes of terms can be substantially automated. ConclusionsThe XPO serves as an example of current best practices to help overcome many of the inherent challenges in harmonizing phenotype data between different species. The XPO currently consists of approximately 22,000 terms and is being used to curate phenotypes by Xenbase, the Xenopus Model Organism Knowledgebase, forming a standardized corpus of genotype-phenotype data that can be directly related to other uPheno compliant resources.

bioinformatics↗

The protein repertoire in early vertebrate embryogenesis

We present an unprecedentedly comprehensive characterization of protein dynamics across early development in Xenopus laevis, available immediately via a convenient Web portal. This resource allows interrogation of the protein expression data in conjunction with other data modalities such as genome wide mRNA expression. This study provides detailed data for absolute levels of [~]14K unique Xenopus proteins representing homologues of [~]9K unique human genes - a rich resource for developmental biologists. The purpose of this manuscript is limited to presenting and releasing the data browser.\n\nHighlightsO_LIRelative protein expression from stage IV oocyte, blastula, gastrula, neurula, and early organogenesis\nC_LIO_LIBiological triplicates with confidence intervals on protein expression reflect certainty in dynamic patterns\nC_LIO_LIConvenient time-series Web-browser integrated with the multi-media Xenbase portal\nC_LIO_LIGene-symbol search and multi-gene protein/mRNA juxtaposition capabilities\nC_LI

developmental biology↗

Systematic Design and Comparison of Expanded Carrier Screening Panels

Purpose: The recent growth in pan-ethnic expanded carrier screening (ECS) has raised questions about how such panels might be designed and evaluated systematically. Design principles for ECS panels might improve clinical detection of at-risk couples and facilitate objective discussions of panel choice.\n\nMethods: Guided by medical-society statements, we propose a method for the design of ECS panels that aims to maximize the aggregate and per-disease sensitivity and specificity across a range of Mendelian disorders considered serious by a systematic classification scheme. We evaluated this method retrospectively using results from 474,644 de-identified carrier screens. We then constructed several idealized panels to highlight strengths and limitations of different ECS methodologies.\n\nResults: Based on modeled fetal risks for \"severe\" and \"profound\" diseases, a commercially available ECS panel (Counsyl) is expected to detect 183 affected conceptuses per 100,000 US births. A screens sensitivity is greatly impacted by two factors: (1) the methodology used (e.g., full-exon sequencing finds up to 46 more affected fetuses per 100,000 than targeted genotyping with an optimal 50 variant panel), and (2) the detection rate of the screen for diseases with high prevalence and complex molecular genetics (e.g., fragile X syndrome, spinal muscular atrophy, 21-hydroxylase deficiency, and alpha-thalassemia account for 54 affected fetuses per 100,000).\n\nConclusion: The described approaches allow principled, quantitative evaluation of which diseases and methodologies are appropriate for pan-ethnic expanded carrier screening.

genetics↗