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

All authors are with the Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA. -- Ulf Martin Singh-Blom is with the Program in Computational and Applied Mathematics, The University of Texas at Austin, Austin, TX 78712, USA, and th Unit of Computational Medicine, Department of Medicine, Karolinska Institutet, Stockholm 171 76, Sweden. -- Kriston L. McGary is with the Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.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.Center for Systems and Synthetic BiologyInstitute for Cellular and Molecular [email protected]

A rockling's choice:The trade-off between thermal preference and physical structure in the five bearded rockling, Ciliata mustela

Changes in the environment can alter the suitability of habitats for organisms. In marine systems, fish species have their own specific requirements in terms of temperature and other habitat features. Behavioral responses such as thermoregulatory behavior in ectothermic species allow mobile organisms to respond to detrimental changes and search for more suitable habitats. However, for many species, limited information exists on the ecological requirements to help explain species abundance in a changing habitat. An example of a quickly changing habitat is the Wadden Sea, where five bearded rockling (Ciliata mustela) abundance has increased, unlike other Wadden Sea species. The increasing abundance of rockling has coincided with increasing average sea water temperatures and the recovery of mussel and Pacific oyster beds. Warming waters and increased structural habitat may have provided rockling with a more desirable habitat. Therefore, to better understand why rockling abundance is increasing within a changing Wadden Sea, a water temperature preference chamber was used to determine rockling's preferred temperature range. In addition, rockling's affinity for structural habitat and the trade-off between preferred temperature was examined by following their response to the systematic removal of artificial physical structures within the preferred temperature conditions. The preferred temperature range of rockling was found to be 10.4–15.7 °C. Following structure removals, rockling repeatedly moved away from their chosen temperatures to adjacent compartments with different temperatures but containing physical structure, indicating that the presence of physical structure was more important than preferred temperature until 18.6 °C. These novel findings provide insight and experimental support for the hypothesis explaining rockling's increase in the Wadden Sea: 1) mean annual temperatures have been steadily increasing towards rockling's preferred thermal range and 2) increasing mussel and Pacific oyster beds are plausibly providing structural habitat, an important habitat requirement for rockling. When fish display a strong association with physical structure it is necessary to link physiological and habitat preferences to better understand climate change related responses

A rockling's choice:The trade-off between thermal preference and physical structure in the five bearded rockling, Ciliata mustela

Changes in the environment can alter the suitability of habitats for organisms. In marine systems, fish species have their own specific requirements in terms of temperature and other habitat features. Behavioral responses such as thermoregulatory behavior in ectothermic species allow mobile organisms to respond to detrimental changes and search for more suitable habitats. However, for many species, limited information exists on the ecological requirements to help explain species abundance in a changing habitat. An example of a quickly changing habitat is the Wadden Sea, where five bearded rockling (Ciliata mustela) abundance has increased, unlike other Wadden Sea species. The increasing abundance of rockling has coincided with increasing average sea water temperatures and the recovery of mussel and Pacific oyster beds. Warming waters and increased structural habitat may have provided rockling with a more desirable habitat. Therefore, to better understand why rockling abundance is increasing within a changing Wadden Sea, a water temperature preference chamber was used to determine rockling's preferred temperature range. In addition, rockling's affinity for structural habitat and the trade-off between preferred temperature was examined by following their response to the systematic removal of artificial physical structures within the preferred temperature conditions. The preferred temperature range of rockling was found to be 10.4–15.7 °C. Following structure removals, rockling repeatedly moved away from their chosen temperatures to adjacent compartments with different temperatures but containing physical structure, indicating that the presence of physical structure was more important than preferred temperature until 18.6 °C. These novel findings provide insight and experimental support for the hypothesis explaining rockling's increase in the Wadden Sea: 1) mean annual temperatures have been steadily increasing towards rockling's preferred thermal range and 2) increasing mussel and Pacific oyster beds are plausibly providing structural habitat, an important habitat requirement for rockling. When fish display a strong association with physical structure it is necessary to link physiological and habitat preferences to better understand climate change related responses

A rockling's choice:The trade-off between thermal preference and physical structure in the five bearded rockling, Ciliata mustela

Changes in the environment can alter the suitability of habitats for organisms. In marine systems, fish species have their own specific requirements in terms of temperature and other habitat features. Behavioral responses such as thermoregulatory behavior in ectothermic species allow mobile organisms to respond to detrimental changes and search for more suitable habitats. However, for many species, limited information exists on the ecological requirements to help explain species abundance in a changing habitat. An example of a quickly changing habitat is the Wadden Sea, where five bearded rockling (Ciliata mustela) abundance has increased, unlike other Wadden Sea species. The increasing abundance of rockling has coincided with increasing average sea water temperatures and the recovery of mussel and Pacific oyster beds. Warming waters and increased structural habitat may have provided rockling with a more desirable habitat. Therefore, to better understand why rockling abundance is increasing within a changing Wadden Sea, a water temperature preference chamber was used to determine rockling's preferred temperature range. In addition, rockling's affinity for structural habitat and the trade-off between preferred temperature was examined by following their response to the systematic removal of artificial physical structures within the preferred temperature conditions. The preferred temperature range of rockling was found to be 10.4–15.7 °C. Following structure removals, rockling repeatedly moved away from their chosen temperatures to adjacent compartments with different temperatures but containing physical structure, indicating that the presence of physical structure was more important than preferred temperature until 18.6 °C. These novel findings provide insight and experimental support for the hypothesis explaining rockling's increase in the Wadden Sea: 1) mean annual temperatures have been steadily increasing towards rockling's preferred thermal range and 2) increasing mussel and Pacific oyster beds are plausibly providing structural habitat, an important habitat requirement for rockling. When fish display a strong association with physical structure it is necessary to link physiological and habitat preferences to better understand climate change related responses

A rockling's choice:The trade-off between thermal preference and physical structure in the five bearded rockling, Ciliata mustela

Changes in the environment can alter the suitability of habitats for organisms. In marine systems, fish species have their own specific requirements in terms of temperature and other habitat features. Behavioral responses such as thermoregulatory behavior in ectothermic species allow mobile organisms to respond to detrimental changes and search for more suitable habitats. However, for many species, limited information exists on the ecological requirements to help explain species abundance in a changing habitat. An example of a quickly changing habitat is the Wadden Sea, where five bearded rockling (Ciliata mustela) abundance has increased, unlike other Wadden Sea species. The increasing abundance of rockling has coincided with increasing average sea water temperatures and the recovery of mussel and Pacific oyster beds. Warming waters and increased structural habitat may have provided rockling with a more desirable habitat. Therefore, to better understand why rockling abundance is increasing within a changing Wadden Sea, a water temperature preference chamber was used to determine rockling's preferred temperature range. In addition, rockling's affinity for structural habitat and the trade-off between preferred temperature was examined by following their response to the systematic removal of artificial physical structures within the preferred temperature conditions. The preferred temperature range of rockling was found to be 10.4–15.7 °C. Following structure removals, rockling repeatedly moved away from their chosen temperatures to adjacent compartments with different temperatures but containing physical structure, indicating that the presence of physical structure was more important than preferred temperature until 18.6 °C. These novel findings provide insight and experimental support for the hypothesis explaining rockling's increase in the Wadden Sea: 1) mean annual temperatures have been steadily increasing towards rockling's preferred thermal range and 2) increasing mussel and Pacific oyster beds are plausibly providing structural habitat, an important habitat requirement for rockling. When fish display a strong association with physical structure it is necessary to link physiological and habitat preferences to better understand climate change related responses

The Early Royal Society and Visual Culture

Recent studies have fruitfully examined the intersection between early modern science and visual culture by elucidating the functions of images in shaping and disseminating scientific knowledge. Given its rich archival sources, it is possible to extend this line of research in the case of the Royal Society to an examination of attitudes towards images as artefacts –manufactured objects worth commissioning, collecting and studying. Drawing on existing scholarship and material from the Royal Society Archives, I discuss Fellows’ interests in prints, drawings, varnishes, colorants, images made out of unusual materials, and methods of identifying the painter from a painting. Knowledge of production processes of images was important to members of the Royal Society, not only as connoisseurs and collectors, but also as those interested in a Baconian mastery of material processes, including a “history of trades”. Their antiquarian interests led to discussion of painters’ styles, and they gradually developed a visual memorial to an institution through portraits and other visual records.AH/M001938/1 (AHRC