Framework for a Protein Ontology

Biomedical ontologies are emerging as critical tools in genomic and proteomic research, where complex data in disparate resources need to be integrated. A number of ontologies describe properties that can be attributed to proteins. For example, protein functions are described by the Gene Ontology (GO) and human diseases by SNOMED CT or ICD10. There is, however, a gap in the current set of ontologies – one that describes the protein entities themselves and their relationships. We have designed the PRotein Ontology (PRO) to facilitate protein annotation and to guide new experiments. The components of PRO extend from the classification of proteins on the basis of evolutionary relationships to the representation of the multiple protein forms of a gene (products generated by genetic variation, alternative splicing, proteolytic cleavage, and other post-translational modifications). PRO will allow the specification of relationships between PRO, GO and other ontologies in the OBO Foundry. Here we describe the initial development of PRO, illustrated using human and mouse proteins involved in the transforming growth factor-beta and bone morphogenetic protein signaling pathways

Expression of Bcl-x in normal skin and benign cutaneous adnexal tumors

10.1111/j.0303-6987.2006.00411.xJournal of Cutaneous Pathology33127-32JCUP

Apoptosis and mitosis in oral and oropharyngeal epithelia: Evidence for a topographical switch in premalignant lesions

Apoptosis (programmed cell death) may play a part in carcinogenesis. The mucosa of the oral cavity, a common site for the development of dysplasia and squamous cell carcinoma, is ideal for the study of carcinogenesis in vivo. Earlier work suggested that apoptosis falls with the development of carcinoma, and that carcinogenesis is preceded by topographical changes in apoptosis. To explore these hypotheses, 72 paraffin sections were obtained: 15 normal (N), nine mild dysplasia (D), 15 severe dysplasia/carcinoma in situ (CIS), 30 squamous cell carcinoma (SCC: power analysis suggested 15 per group). Apoptotic (AI) and mitotic (MI) indices and AT/MI ratio were calculated (1000 cells/slide). These, with age, sex, alcohol and smoking habits, and anatomical subsite, were entered into a regression model with histological group as dependent. Vertical cell position (cp) was plotted, and resultant frequency curves were compared. MI significantly increased (mean N 0.39, 95% confidence interval 0-0.35; D 0.63, 0.23-0.98; SCC 0.86, 0.51-1.21, P < 0.0001) and AI/MI significantly decreased (D 0.54, 0.20-0.86; SCC 0.28, 0.05-0.61, P < 0.05) progressing from D, through CIS, to SCC. However, after inclusion of all variables, only MI remained significant (P < 0.0001). Peak incidence of mitosis shifted downwards in CIS relative to N and D, whilst peak apoptosis shifted upwards. Thus, programmed cell death remains static as mitosis increases in carcinogenesis of the oral cavity. However, there is an alteration in the topographical relationship of these events in CIS which may make homeostatic mechanisms involving apoptosis less efficient