Authoring bio-ontologies is a task that has traditionally been undertaken by skilled experts trained in understanding complex languages such as the Web Ontology Language (OWL), in tools designed for ...such experts. As requests for new terms are made, the need for expert ontologists represents a bottleneck in the development process. Furthermore, the ability to rigorously enforce ontology design patterns in large, collaboratively developed ontologies is difficult with existing ontology authoring software.
We present Webulous, an application suite for supporting ontology creation by design patterns. Webulous provides infrastructure to specify templates for populating ontology design patterns that get transformed into OWL assertions in a target ontology. Webulous provides programmatic access to the template server and a client application has been developed for Google Sheets that allows templates to be loaded, populated and resubmitted to the Webulous server for processing.
The development and delivery of ontologies to the community requires software support that goes beyond the ontology editor. Building ontologies by design patterns and providing simple mechanisms for the addition of new content helps reduce the overall cost and effort required to develop an ontology. The Webulous system provides support for this process and is used as part of the development of several ontologies at the European Bioinformatics Institute.
Gene functional annotations are an essential part of knowledge discovery in the analysis of large datasets, with the Gene Ontology Ashburner et al., 2000 as the de facto standard for such ...annotations. A considerable number of approaches for quantifying functional similarity between gene products based on the semantic similarity between their annotations have been developed, but little guidance exists as to which of these measures are the most appropriate for different purposes. This was addressed here by comparing the performances of a number of similarity measures and associated parameters. This comparison provided some interesting new insights as well as confirming emerging trends from the literature. There is also a pressing need for novel ways of applying these measures to facilitate the functional analysis of lists of gene products. We developed a novel algorithm, FuSiGroups, to group GO terms based on their semantic similarity and genes based on their functional similarity. This two-fold grouping results in groups of not only functionally similar genes but also an associated set of related GO terms that characterise a single functional aspect relating the genes in the group, which facilitates analysis by creating more coherent groups. Each gene can belong to multiple groups, so the groups more accurately reflect the complexity of biological reality than clusters generated using traditional approaches. FuSiGroups was tested on a number of scenarios and in each case, successfully generated biologically relevant groups, identifying the key functional aspects of the dataset. The algorithm also managed to eliminate genes that were functionally unrelated to the bulk of the dataset and distinguish between different biological pathways. Although dataset size is currently a limiting factor, with smaller datasets performing the best, FuSiGroups has been demonstrated as a promising approach for the functional analysis of gene products.
Gene functional annotations are an essential part of knowledge discovery in the analysis of large datasets, with the Gene Ontology Ashburner et al., 2000 as the de facto standard for such ...annotations. A considerable number of approaches for quantifying functional similarity between gene products based on the semantic similarity between their annotations have been developed, but little guidance exists as to which of these measures are the most appropriate for different purposes. This was addressed here by comparing the performances of a number of similarity measures and associated parameters. This comparison provided some interesting new insights as well as confirming emerging trends from the literature. There is also a pressing need for novel ways of applying these measures to facilitate the functional analysis of lists of gene products. We developed a novel algorithm, FuSiGroups, to group GO terms based on their semantic similarity and genes based on their functional similarity. This two-fold grouping results in groups of not only functionally similar genes but also an associated set of related GO terms that characterise a single functional aspect relating the genes in the group, which facilitates analysis by creating more coherent groups. Each gene can belong to multiple groups, so the groups more accurately reflect the complexity of biological reality than clusters generated using traditional approaches. FuSiGroups was tested on a number of scenarios and in each case, successfully generated biologically relevant groups, identifying the key functional aspects of the dataset. The algorithm also managed to eliminate genes that were functionally unrelated to the bulk of the dataset and distinguish between different biological pathways. Although dataset size is currently a limiting factor, with smaller datasets performing the best, FuSiGroups has been demonstrated as a promising approach for the functional analysis of gene products.
The project sets out to investigate the concept of semantic similarity between individual and collections of gene products based on functional descriptors such as “Gene Ontology” (GO) annotations. ...Different existing concepts for quantifying semantic similarity are implemented into a basic “Semantic Similarity Calculator” and the resulting tool applied to assess its utility in different biological contexts. It is discussed what kinds of problems were encountered during the implementation of the prototype, and how these problems were addressed, or are planned to be addressed in the future. An overview over future work is given.
To predict the effectiveness of land reclamation, it is important to understand how water and solutes are transported within reconstructed landscapes. The objective of this study was to examine the ...influence of preferential flow on salt leaching in reclamation soil covers. The study site was a reconstructed landscape where saline-sodic minespoil from oil sands mining was capped with layers of glacial and peat mix soil. Preferential flow was investigated using laboratory column experiments and in situ adsorptive dye and conservative tracer experiments.
Results from column experiments and dye tracer experiments indicate that preferential flow is an important and prevalent mechanism of solute transport. Column experiments, which used time-domain reflectometry to monitor the transport of a chloride tracer through an undisturbed core of peat mix soil, determined immobile water fractions (èim/è) ranging from 80-99% and diffusive mass transfer rates (á) between 0.15 - 2.0 h-1. Breakthrough curves showed the early arrival of chloride and extended tailing. Dye tracer experiments, in which Brilliant Blue dye was applied in solution to the soil surface, were carried out at 6 hillslopes plots. Approximately 24 hours after dye application, a vertical soil face was excavated to reveal stained flow patterns. Preferential flow as macropore flow, fingering, and / or funneling was observed at each plot.
Results from the conservative tracer field study indicated soil solutes were flushed by a combination of vertical and lateral flow processes. A large pulse of bromide and chloride was applied across the lower slope of the 0.35-m cover. Soil sampling at approximately 1 and 2 years later determined vertical leaching, lateral translocation downslope, and upwards movement of soil solutes. Matrix flow during the spring melt, combined with matrix flow and / or preferential flow during summer and fall periods, was responsible for the vertical leaching of solutes. Subsurface flow generated in response to the spring melt or due to differences in soil hydraulic conductivity was responsible for the lateral transport of solutes. As a result of advective or diffusive processes, solutes were transported upwards into the overlying soil. These results suggested that despite the existence of preferential flow, there were other mechanisms of solute transport which served to leach and flush salts from the soil.
To predict the effectiveness of land reclamation, it is important to understand how water and solutes are transported within reconstructed landscapes. The objective of this study was to examine the ...influence of preferential flow on salt leaching in reclamation soil covers. The study site was a reconstructed landscape where saline-sodic minespoil from oil sands mining was capped with layers of glacial and peat mix soil. Preferential flow was investigated using laboratory column experiments and in situ adsorptive dye and conservative tracer experiments.
Results from column experiments and dye tracer experiments indicate that preferential flow is an important and prevalent mechanism of solute transport. Column experiments, which used time-domain reflectometry to monitor the transport of a chloride tracer through an undisturbed core of peat mix soil, determined immobile water fractions (èim/è) ranging from 80-99% and diffusive mass transfer rates (á) between 0.15 - 2.0 h-1. Breakthrough curves showed the early arrival of chloride and extended tailing. Dye tracer experiments, in which Brilliant Blue dye was applied in solution to the soil surface, were carried out at 6 hillslopes plots. Approximately 24 hours after dye application, a vertical soil face was excavated to reveal stained flow patterns. Preferential flow as macropore flow, fingering, and / or funneling was observed at each plot.
Results from the conservative tracer field study indicated soil solutes were flushed by a combination of vertical and lateral flow processes. A large pulse of bromide and chloride was applied across the lower slope of the 0.35-m cover. Soil sampling at approximately 1 and 2 years later determined vertical leaching, lateral translocation downslope, and upwards movement of soil solutes. Matrix flow during the spring melt, combined with matrix flow and / or preferential flow during summer and fall periods, was responsible for the vertical leaching of solutes. Subsurface flow generated in response to the spring melt or due to differences in soil hydraulic conductivity was responsible for the lateral transport of solutes. As a result of advective or diffusive processes, solutes were transported upwards into the overlying soil. These results suggested that despite the existence of preferential flow, there were other mechanisms of solute transport which served to leach and flush salts from the soil.
Background
New York State (NYS) utilizes a three‐tiered cystic fibrosis newborn screening (CFNBS) algorithm that includes cystic fibrosis transmembrane conductance regulator (CFTR) gene sequencing. ...Infants with >1 CFTR variant of potential clinical relevance, including variants of uncertain significance or varying clinical consequence are referred for diagnostic evaluation at NYS cystic fibrosis (CF) Specialty Care Centers (SCCs).
Aims
As part of ongoing quality improvement efforts, demographic, screening, diagnostic, and clinical data were evaluated for 289 CFNBS‐positive infants identified in NYS between December 2017 and November 2020 who did not meet diagnostic criteria for CF and were classified as either: CFTR‐related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) or CF carriers.
Results
Overall, 194/289 (67.1%) had CFTR phasing to confirm whether the infant's CFTR variants were in cis or in trans. Eighteen complex alleles were identified in cis; known haplotypes (p.R117H+5T, p.F508del+p.L467F, and p.R74W+p.D1270N) were the most common identified. Thirty‐two infants (16.5%) with all variants in cis were reclassified as CF carriers rather than CRMS/CFSPID. Among 263 infants evaluated at an NYS SCC, 70.3% were reported as having received genetic counseling about their results by any provider, with 96/263 (36.5%) counseled by a certified genetic counselor.
Conclusion
Given the particularly complex genetic interpretation of results generated by CFNBS algorithms including sequencing analysis, additional efforts are needed to ensure families of infants with a positive CFNBS result have CFTR phasing when needed to distinguish carriers from infants with CRMS/CFSPID, and access to genetic counseling to address implications of CFNBS results.
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