TGF-beta signaling proteins and the Protein Ontology

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides a framework for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses

The Non-Coding RNA Ontology : a comprehensive resource for the unification of non-coding RNA biology

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users

Automated Annotation-Based Bio-Ontology Alignment with Structural Validation

We outline the structure of an automated process to both align multiple bio-ontologies in terms of their genomic co-annotations, and then to measure the structural quality of that alignment. We illustrate the method with a genomic analysis of 70 genes implicated in lung disease against the Gene Ontology

The development of non-coding RNA ontology

Identification of non-coding RNAs (ncRNAs) has been significantly improved over the past decade. On the other hand, semantic annotation of ncRNA data is facing critical challenges due to the lack of a comprehensive ontology to serve as common data elements and data exchange standards in the field. We developed the Non-Coding RNA Ontology (NCRO) to handle this situation. By providing a formally defined ncRNA controlled vocabulary, the NCRO aims to fill a specific and highly needed niche in semantic annotation of large amounts of ncRNA biological and clinical data

A domain ontology for the non-coding RNA field

Identification of non-coding RNAs (ncRNAs) has been significantly enhanced due to the rapid advancement in sequencing technologies. On the other hand, semantic annotation of ncRNA data lag behind their identification, and there is a great need to effectively integrate discovery from relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a precisely defined ncRNA controlled vocabulary, which can fill a specific and highly needed niche in unification of ncRNA biology

The representation of protein complexes in the Protein Ontology

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/

Protein Ontology: A controlled structured network of protein entities

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments

Pax3 expression in cutaneous malignant melanoma

This research investigated the repercussions of aberrant PAX3 re-expression in cutaneous malignant melanoma (CMM). The transcription, factor encoded by PAX is amongst the first expressed in the embryo, with a principal role in the development of the melanocytic lineage. We theorised that abnormal re-expression of PAX3, consistently observed in CMM as compared to normal melanocytes, is linked to progression of CMM. Previous studies have stated that expression profiles of PAX3 in CMM demonstrate predominant generation of a protein encoded by exons 1-9 (PAX3D) utilizing cryptic splice sites in post-transcriptional pre-mRNA splicing. By contrast, normal human skin demonstrates low level generation of PAX3C (encoded by exons 1-8). Using RT-PCR based techniques and immunohistochemistry, we present original evidence of Pax3c, Pax3d mRNA and protein expression in normal murine embryogenesis and melanogenesis, identifying a conserved role for the Pax3d protein in transcriptional regulation of the murine melanoblast. Furthermore, to identify a role for Pax3 in adult skin, we used a reliable time-scale for the strict coupling of melanogenesis to active hair regrowth; Pax3c and Pax3d expression profiles were assessed during depilation experiments which induced murine malanocytic stem cells to proliferate, migrate into the hair cortex and differentiate in order to produce melanin for new hair. Results indicate that strict temporal expression of Pax3d may be linked to either melanoblast proliferation or migration in early melanogenesis thus supporting a possible role for PAX3D in the tumourigenesis of CMM

The characterisation of Pax3 expressant cells in adult peripheral nerve

Pax3 has numerous integral functions in embryonic tissue morphogenesis while knowledge of its complex function in cells of adult tissue continues to unfold. Across a variety of adult tissue lineages, the role of Pax3 is principally linked to maintenance of the tissue’s resident stem and progenitor cell population. In adult peripheral nerves, Pax3 is reported to be expressed in nonmyelinating Schwann cells, however, little is known about the purpose of this expression. Based on the evidence of its role in other adult tissue stem and progenitor cell maintenance, it was hypothesised that the cells in adult peripheral nerve that express Pax3 may be Schwann glioblasts. Here, methods have been developed for visualisation of Pax3 expressant cells in normal 60 day old mouse peripheral nerve. Visualisation allowed morphological, anatomical and phenotypic distinctions to be made between these Pax3 expressing cells and Remak bundle nonmyelinating Schwann cells. The distinctions described herein, together with the finding that Pax3 expressing cells co-express stem cell marker Sox2, provides compelling support for the suggestion that a progenitor Schwann cell population may be present in adult mouse peripheral nerve