Prediction of gene-phenotype associations in humans, mice, and plants using phenologs.

BACKGROUND: Phenotypes and diseases may be related to seemingly dissimilar phenotypes in other species by means of the orthology of underlying genes. Such "orthologous phenotypes," or "phenologs," are examples of deep homology, and may be used to predict additional candidate disease genes. RESULTS: In this work, we develop an unsupervised algorithm for ranking phenolog-based candidate disease genes through the integration of predictions from the k nearest neighbor phenologs, comparing classifiers and weighting functions by cross-validation. We also improve upon the original method by extending the theory to paralogous phenotypes. Our algorithm makes use of additional phenotype data--from chicken, zebrafish, and E. coli, as well as new datasets for C. elegans--establishing that several types of annotations may be treated as phenotypes. We demonstrate the use of our algorithm to predict novel candidate genes for human atrial fibrillation (such as HRH2, ATP4A, ATP4B, and HOPX) and epilepsy (e.g., PAX6 and NKX2-1). We suggest gene candidates for pharmacologically-induced seizures in mouse, solely based on orthologous phenotypes from E. coli. We also explore the prediction of plant gene-phenotype associations, as for the Arabidopsis response to vernalization phenotype. CONCLUSIONS: We are able to rank gene predictions for a significant portion of the diseases in the Online Mendelian Inheritance in Man database. Additionally, our method suggests candidate genes for mammalian seizures based only on bacterial phenotypes and gene orthology. We demonstrate that phenotype information may come from diverse sources, including drug sensitivities, gene ontology biological processes, and in situ hybridization annotations. Finally, we offer testable candidates for a variety of human diseases, plant traits, and other classes of phenotypes across a wide array of species.

Evaluation of ColdZyme® Mouth Spray on prevention of upper respiratory tract infections in a boy with primary immunodeficiency: a case report.

BACKGROUND: Primary immunodeficiencies include a variety of disorders that render patients more susceptible to infections. If left untreated, these infections may be fatal. Patients with primary antibody deficiencies are therefore given prophylactic immunoglobulin G replacement therapy. ColdZyme® Mouth Spray is a medical device intended to reduce the probability of catching a cold and/or can help shorten the duration of a cold, if used at an early stage of the infection, by forming a thin protective barrier on the pharyngeal mucous membrane. This is the first report of this kind in the literature. CASE PRESENTATION: The parents of a 12-year-old white boy diagnosed as having common variable immunodeficiency voluntarily started to let their son use ColdZyme® Mouth Spray to reduce common cold infections if possible. Prior to using ColdZyme® Mouth Spray, he had recurrent microbial infections of his ears, sinuses, nose, bronchi, and lungs. He also frequently exhibited continuous rhinorrhea, fungal growth in his oral cavity, and gingivitis with wounds in his gums. As a consequence, his and his family's health-related quality of life was severely compromised. He commenced a twice-daily treatment (morning and evening) with ColdZyme® Mouth Spray; the weekly administration of immunoglobulin G (Hizentra®) for replacement therapy was continued throughout this period. Data were retrieved by using a daily diary about infections and symptoms. His guardians had recorded infection symptoms since he was diagnosed as having common variable immunodeficiency 10 years earlier to follow the effect of the immunoglobulin G treatment. Shortly after commencement of ColdZyme® Mouth Spray treatment, he experienced a marked improvement in symptoms and health-related quality of life. His continuous rhinorrhea disappeared, breathing through his nose was easier, oral fungal infection decreased, and wounds in his gum tissue healed for the first time in several years. CONCLUSIONS: We observed that when ColdZyme® Mouth Spray was used to reduce common cold viral infection in a patient with common variable immunodeficiency on immunoglobulin G replacement therapy, secondary microbial and fungal infections in his oral cavity and oropharynx were also reduced. A controlled study is warranted to confirm the observed results.