The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.Peer reviewe

Prediction of emergency department patient disposition decision for proactive resource allocation for admission.

We investigate the capability of information from electronic health records of an emergency department (ED) to predict patient disposition decisions for reducing boarding delays through the proactive initiation of admission processes (e.g., inpatient bed requests, transport, etc.). We model the process of ED disposition decision prediction as a hierarchical multiclass classification while dealing with the progressive accrual of clinical information throughout the ED caregiving process. Multinomial logistic regression as well as machine learning models are built for carrying out the predictions. Utilizing results from just the first set of ED laboratory tests along with other prior information gathered for each patient (2.5 h ahead of the actual disposition decision on average), our model predicts disposition decisions with positive predictive values of 55.4%, 45.1%, 56.9%, and 47.5%, while controlling false positive rates (1.4%, 1.0%, 4.3%, and 1.4%), with AUC values of 0.97, 0.95, 0.89, and 0.84 for the four admission (minor) classes, i.e., intensive care unit (3.6% of the testing samples), telemetry unit (2.2%), general practice unit (11.9%), and observation unit (6.6%) classes, respectively. Moreover, patients destined to intensive care unit present a more drastic increment in prediction quality at triage than others. Disposition decision classification models can provide more actionable information than a binary admission vs. discharge prediction model for the proactive initiation of admission processes for ED patients. Observing the distinct trajectories of information accrual and prediction quality evolvement for ED patients destined to different types of units, proactive coordination strategies should be tailored accordingly for each destination unit

The epidemiology and economic impact of varicella-related hospitalizations in Turkey from 2008 to 2010: A nationwide survey during the pre-vaccine era (VARICOMP study)

PubMed ID: 22170238Varicella can cause complications that are potentially serious and require hospitalization. Our current understanding of the causes and incidence of varicella-related hospitalization in Turkey is limited and sufficiently accurate epidemiological and economical information is lacking. The aim of this study was to estimate the annual incidence of varicella-related hospitalizations, describe the complications, and estimate the annual mortality and cost of varicella in children. VARICOMP is a multi-center study that was performed to provide epidemiological and economic data on hospitalization for varicella in children between 0 and 15 years of age from October 2008 to September 2010 in Turkey. According to medical records from 27 health care centers in 14 cities (representing 49.3% of the childhood population in Turkey), 824 children (73% previously healthy) were hospitalized for varicella over the 2-year period. Most cases occurred in the spring and early summer months. Most cases were in children under 5 years of age, and 29.5% were in children under 1 year of age. The estimated incidence of varicella-related hospitalization was 5.29-6.89 per 100,000 in all children between 0-15 years of age in Turkey, 21.7 to 28 per 100,000 children under 1 year of age, 9.8-13.8 per 100,000 children under 5 years of age, 3.96-6.52 per 100,000 children between 5 and 10 years of age and 0.42 to 0.71 per 100,000 children between 10 and 15 years of age. Among the 824 children, 212 (25.7%) were hospitalized because of primary varicella infection. The most common complications in children were secondary bacterial infection (23%), neurological (19.1%), and respiratory (17.5%) complications. Secondary bacterial infections (p<0.001) and neurological complications (p<0.001) were significantly more common in previously healthy children, whereas hematological complications (p<0.001) were more commonly observed in children with underlying conditions. The median length of the hospital stay was 6 days, and it was longer in children with underlying conditions (<0.001). The median cost of hospitalization per patient was $338 and was significantly higher in children with underlying conditions (p<0.001). The estimated direct annual cost (not including the loss of parental work time and school absence) of varicella-related hospitalization in children under the age of 15 years in Turkey was$856,190 to $1,407,006. According to our estimates, 882 to 1,450 children are hospitalized for varicella each year, reflecting a population-wide occurrence of 466-768 varicella cases per 100,000 children. In conclusion, this study confirms that varicella-related hospitalizations are not uncommon in children, and two thirds of these children are otherwise healthy. The annual cost of hospitalization for varicella reflects only a small part of the overall cost of this disease, as only a very few cases require hospital admission. The incidence of this disease was higher in children <1 year of age, and there are no prevention strategies for these children other than population-wide vaccination. Universal vaccination is therefore the only realistic option for the prevention of severe complications and deaths. The surveillance of varicellaassociated complications is essential for monitoring of the impact of varicella immunization. © Springer-Verlag 2011