Engineering topics

Segerdell, Erik

Publications and source records attributed to Segerdell, Erik.

4 records

DOE OSTI2019

The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species

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. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2015

Finding Our Way through Phenotypes

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, consensusbased, 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. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today’s data barriers and facilitate analytical reproducibility.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2014

The Porifera Ontology (PORO): enhancing sponge systematics with an anatomy ontology

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. However, much of the knowledge of these organisms has not previously been codified in a machine-readable way using modern web standards. Results: The Porifera Ontology is intended as a standardized coding system for sponge anatomical features currently used in systematics. The ontology is available from http://purl.obolibrary.org/obo/poro.owl, or from the project homepage http://porifera-ontology.googlecode.com/. The version referred to in this manuscript is permanently available from http://purl.obolibrary.org/obo/poro/releases/2014-03-06/. Conclusions: By standardizing character representations, we hope to facilitate more rapid description and identification of sponge taxa, to allow integration with other evolutionary database systems, and to perform character mapping across the major clades of sponges to better understand the evolution of morphological features. Future applications of the ontology will focus on creating (1) ontology-based species descriptions; (2) taxonomic keys that use the nested terms of the ontology to more quickly facilitate species identifications; and (3) methods to map anatomical characters onto molecular phylogenies of sponges. In addition to modern taxa, the ontology is being extended to include features of fossil taxa.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2012

A Unified Anatomy Ontology of the Vertebrate Skeletal System

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. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity

59 BASIC BIOLOGICAL SCIENCES↗