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Natural language descriptions of organismal phenotypes, a principal object of study in biology, are abundant in the biological literature. Expressing these phenotypes as logical statements using ontologies would enable large-scale analysis on phenotypic information from diverse systems. However, considerable human effort is required to make these phenotype descriptions amenable to machine reasoning. Natural language processing tools have been developed to facilitate this task, and the training and evaluation of these tools depend on the availability of high quality, manually annotated gold standard data sets. We describe the development of an expert-curated gold standard data set of annotated phenotypes for evolutionary biology. The gold standard was developed for the curation of complex comparative phenotypes for the Phenoscape project. It was created by consensus among three curators and consists of entity-quality expressions of varying complexity. We use the gold standard to evaluate annotations created by human curators and those generated by the Semantic CharaParser tool. Using four annotation accuracy metrics that can account for any level of relationship between terms from two phenotype annotations, we found that machine-human consistency, or similarity, was significantly lower than inter-curator (human-human) consistency. Surprisingly, allowing curatorsaccess to external information did not significantly increase the similarity of their annotations to the gold standard or have a significant effect on inter-curator consistency. We found that the similarity of machine annotations to the gold standard increased after new relevant ontology terms had been added. Evaluation by the original authors of the character descriptions indicated that the gold standard annotations came closer to representing their intended meaning than did either the curator or machine annotations. These findings point toward ways to better design software to augment human curators and the use of the gold standard corpus will allow training and assessment of new tools to improve phenotype annotation accuracy at scale.

The predictive properties of four definitions of a frailty risk score (FRS) constructed using combinations of nursing flowsheet data, laboratory tests, and ICD-10 codes were examined for time to first intensive care unit (ICU) transfer in medical-surgical inpatients ≥50 years of age. Cox regression modeled time to first ICU transfer and Schemper–Henderson explained variance summarized predictive accuracy of FRS combinations. Modeling by age group and controlling for sex, all FRS measures significantly predicted time to first ICU transfer. Further multivariable modeling controlling for clinical characteristics substantially improved predictive accuracy. The effect of frailty on time to first ICU transfer depended on age, with highest risk in 50 to <60 years and ≥80 years age groups. Frailty prevalence ranged from 25.1% to 56.4%. Findings indicate that FRS-based frailty is a risk factor for time to first ICU transfer and should be considered in assessment and care-planning to address frailty in high-risk patients. Frailty prevalence was highest med-surg pts 60 to <70 years (56%); highest risk for time to first ICU transfer was in younger (50 to <60 years) and older (≥80 years) groups. [ABSTRACT FROM AUTHOR]

Abstract Background Functional genomics technologies that measure genome expression at a global scale are accelerating biological knowledge discovery. Generating these high throughput datasets is relatively easy compared to the downstream functional modelling necessary for elucidating the molecular mechanisms that govern the biology under investigation. A number of publicly available ‘discovery-based’ computational tools use the computationally amenable Gene Ontology (GO) for hypothesis generation. However, there are few tools that support hypothesis-based testing using the GO and none that support testing with user defined hypothesis terms. Here, we present GOModeler, a tool that enables researchers to conduct hypothesis-based testing of high throughput datasets using the GO. GOModeler summarizes the overall effect of a user defined gene/protein differential expression dataset on specific GO hypothesis terms selected by the user to describe a biological experiment. The design of the tool allows the user to complement the functional information in the GO with his/her domain specific expertise for comprehensive hypothesis testing. Results GOModeler tests the relevance of the hypothesis terms chosen by the user for the input gene dataset by providing the individual effects of the genes on the hypothesis terms and the overall effect of the entire dataset on each of the hypothesis terms. It matches the GO identifiers (ids) of the genes with the GO ids of the hypothesis terms and parses the names of those ids that match to assign effects. We demonstrate the capabilities of GOModeler with a dataset of nine differentially expressed cytokine genes and compare the results to those obtained through manual analysis of the dataset by an immunologist. The direction of overall effects on all hypothesis terms except one was consistent with the results obtained by manual analysis. The tool’s editing capability enables the user to augment the information extracted. GOModeler is available as a part of the AgBase tool suite (http://www.agbase.msstate.edu). Conclusions GOModeler allows hypothesis driven analysis of high throughput datasets using the GO. Using this tool, researchers can quickly evaluate the overall effect of quantitative expression changes of gene set on specific biological processes of interest. The results are provided in both tabular and graphical formats.

Abstract The widespread availability of microarray technology has driven functional genomics to the forefront as scientists seek to draw meaningful biological conclusions from their microarray results. Gene annotation enrichment analysis is a functional analysis technique that has gained widespread attention and for which many tools have been developed. Unfortunately, most of these tools have limited support for agricultural species. Here, we evaluate and compare four publicly available computational tools (Onto-Express, EasyGO, GOstat, and DAVID) that support analysis of gene expression datasets in agricultural species. We use AgBase as the functional annotation reference for agricultural species. The selected tools were evaluated based on i) available features, usage and accessibility, ii) implemented statistical computational methods, and iii) annotation and enrichment performance analysis. Annotation was assessed using a randomly selected test gene annotation set and an experimental differentially expressed gene-set – both from chicken. The experimental set was also used to evaluate identification of enriched functional groups. Comparison of the tools shows that they produce different sets of annotations for the two datasets and different functional groups for the experimental dataset. While DAVID, GOstat and Onto-Express annotate comparable numbers of genes, DAVID provides by far the most annotations per gene. However, many of DAVID's annotations appear to be redundant or are at very high levels in the GO hierarchy. The GOSlim distribution of annotations shows that GOstat, Onto-Express and EasyGO provide similar GO distributions to those found in AgBase while annotations from DAVID show a different GOSlim distribution, again probably due to duplication and many non-specific terms. No consistent trends were found in results of GO term over/under representation analysis applied to the experimental data using different tools. While GOstat, David and Onto-Express could retrieve some significantly enriched terms, EasyGO did not show any significantly enriched terms. There was little agreement about the enriched terms identified by the tools. Conclusion Different tools for functionally annotating gene sets and identifying significantly enriched GO categories differ widely in their results when applied to a test annotation gene set and an experimental dataset from chicken. These results emphasize the need for care when interpreting the results of such analysis and the lack of standardization of approaches.

Purpose: The purpose of this study was to evaluate four definitions of a Frailty Risk Score (FRS) derived from EHR data that includes combinations of biopsychosocial risk factors using nursing flowsheet data or International Classification of Disease, 10th revision (ICD-10) codes and blood biomarkers and its predictive properties for in-hospital mortality in adults ≥50 years admitted to medical-surgical units. Methods In this retrospective observational study and secondary analysis of an EHR dataset, survival analysis and Cox regression models were performed with sociodemographic and clinical covariates. Integrated area under the ROC curve (iAUC) across follow-up time based on Cox modeling was estimated. Results The 46,645 patients averaged 1.5 hospitalizations (SD = 1.1) over the study period and 63.3% were emergent admissions. The average age was 70.4 years (SD = 11.4), 55.3% were female, 73.0% were non-Hispanic White (73.0%), mean comorbidity score was 3.9 (SD = 2.9), 80.5% were taking 1.5 high risk medications, and 42% recorded polypharmacy. The best performing FRS-NF-26-LABS included nursing flowsheet data and blood biomarkers (Adj. HR = 1.30, 95% CI [1.28, 1.33]), with good accuracy (iAUC =.794); the reduced model with age, sex, and FRS only demonstrated similar accuracy. The poorest performance was the ICD-10 code-based FRS. Conclusion The FRS captures information about the patient that increases risk for in-hospital mortality not accounted for by other factors. Identification of frailty enables providers to enhance various aspects of care, including increased monitoring, applying more intensive, individualized resources, and initiating more informed discussions about treatments and discharge planning. [ABSTRACT FROM AUTHOR]