Publications by authors named "Erik Segerdell"

Article Synopsis
  • Phenotypic data helps us understand how genomic variations affect living organisms and is vital for clinical applications like diagnosing diseases and developing treatments.
  • The field of phenomics aims to unify and analyze the vast amounts of phenotypic data collected over time, but faces challenges due to inconsistent methods and vocabularies used to record this information.
  • The Unified Phenotype Ontology (uPheno) framework offers a solution by providing a standardized system for organizing phenotype terms, allowing for better integration of data across different species and improving research on genotype-phenotype associations.
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Xenbase (https://www.xenbase.org/), the Xenopus model organism knowledgebase, is a web-accessible resource that integrates the diverse genomic and biological data from research on the laboratory frogs Xenopus laevis and Xenopus tropicalis.

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Background: Ontologies 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.

Results: Here 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.

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In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven't been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search.

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Ocular toxoplasmosis is the commonest clinical manifestation of infection with obligate intracellular parasite, . Active ocular toxoplasmosis is characterized by replication of tachyzoites in the retina, with reactive inflammation. The multifunctional retinal pigment epithelium is a key target cell population for .

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At a fundamental level most genes, signaling pathways, biological functions and organ systems are highly conserved between man and all vertebrate species. Leveraging this conservation, researchers are increasingly using the experimental advantages of the amphibian to model human disease. The online resource, Xenbase, enables human disease modeling by curating the literature published in PubMed and integrating these data with orthologous human genes, anatomy, and more recently with links to the Online Mendelian Inheritance in Man resource (OMIM) and the Human Disease Ontology (DO).

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FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs.

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Article Synopsis
  • The Beat AML program analyzed tumor specimens from 562 AML patients to examine complex mutations and drug responses using whole-exome and RNA sequencing.* -
  • The study discovered previously undetected mutations and identified how certain drug responses are linked to specific combinations of these mutations.* -
  • Findings, including gene expression signatures related to drug responses, are available through the Beat AML data viewer, enabling further research on AML biology.*
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Xenbase is the Xenopus model organism database ( www.xenbase.org ), a web-accessible resource that integrates the diverse genomic and biological data for Xenopus research.

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Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes.

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Background: Porifera (sponges) are ancient basal metazoans that lack organs. They provide insight into key evolutionary transitions, such as the emergence of multicellularity and the nervous system. In addition, their ability to synthesize unusual compounds offers potential biotechnical applications.

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Background: The African clawed frogs Xenopus laevis and Xenopus tropicalis are prominent animal model organisms. Xenopus research contributes to the understanding of genetic, developmental and molecular mechanisms underlying human disease. The Xenopus Anatomy Ontology (XAO) reflects the anatomy and embryological development of Xenopus.

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The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology.

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Xenbase (http://www.xenbase.org) is a model organism database that provides genomic, molecular, cellular and developmental biology content to biomedical researchers working with the frog, Xenopus and Xenopus data to workers using other model organisms.

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Development of biocuration processes and guidelines for new data types or projects is a challenging task. Each project finds its way toward defining annotation standards and ensuring data consistency with varying degrees of planning and different tools to support and/or report on consistency. Further, this process may be data type specific even within the context of a single project.

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Xenbase (www.xenbase.org), the model organism database for Xenopus laevis and X.

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Background: The frogs Xenopus laevis and Xenopus (Silurana) tropicalis are model systems that have produced a wealth of genetic, genomic, and developmental information. Xenbase is a model organism database that provides centralized access to this information, including gene function data from high-throughput screens and the scientific literature. A controlled, structured vocabulary for Xenopus anatomy and development is essential for organizing these data.

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The Zebrafish Information Network (ZFIN, http://zfin.org), the model organism database for zebrafish, provides the central location for curated zebrafish genetic, genomic and developmental data. Extensive data integration of mutant phenotypes, genes, expression patterns, sequences, genetic markers, morpholinos, map positions, publications and community resources facilitates the use of the zebrafish as a model for studying gene function, development, behavior and disease.

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Xenbase (www.xenbase.org) is a model organism database integrating a diverse array of biological and genomic data on the frogs, Xenopus laevis and Xenopus (Silurana) tropicalis.

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Understanding the developmental and genetic underpinnings of particular evolutionary changes has been hindered by inadequate databases of evolutionary anatomy and by the lack of a computational approach to identify underlying candidate genes and regulators. By contrast, model organism studies have been enhanced by ontologies shared among genomic databases. Here, we suggest that evolutionary and genomics databases can be developed to exchange and use information through shared phenotype and anatomy ontologies.

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The Zebrafish Information Network (ZFIN; http://zfin.org) is a web based community resource that implements the curation of zebrafish genetic, genomic and developmental data. ZFIN provides an integrated representation of mutants, genes, genetic markers, mapping panels, publications and community resources such as meeting announcements and contact information.

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The systematic assignment of gene function to a sequenced genome is one of the outstanding challenges in the post-genomic era. Large-scale systematic mutagenesis screens are important tools for reaching this goal. Here we describe GSD, a software package that allows storage and integration of data from genetic screens.

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The Zebrafish Information Network (ZFIN) is a web based community resource that serves as a centralized location for the curation and integration of zebrafish genetic, genomic and developmental data. ZFIN is publicly accessible at http://zfin.org.

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