The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. 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 (P. aureginosa only). We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. 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 expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. We finally report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bioontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens. 157 project. Predicting GO terms for a protein (protein-centric) and predicting which proteins are associated 158 with a given function (term-centric) are related but different computational problems: the former is a 159 multi-label classification problem with a structured output, while the latter is a binary classification task. 160Predicting the results of a genome-wide screen for a single or a small number of functions fits the term-centric 161 formulation. To see how well all participating CAFA methods perform term-centric predictions, we mapped 162 results from the protein-centric CAFA3 methods onto these terms. In addition we held a separate CAFA 163 challenge, CAFA-π whose purpose was to attract additional submissions from algorithms that specialize in 164 term-centric tasks. 165 We performed screens for three functions in three species, which we then used to assess protein function 166 prediction. In the bacterium Pseudomonas aeruginosa and the fungus Candida albicans we performed 167 genome-wide screens capable of uncovering genes with two functions, biofilm formation (GO:0042710) and 168 motility (for P. aeruginosa only) (GO:0001539), as described in Methods. In Drosophila melanogaster we 169 performed targeted assays, guided by previous CAFA submissions, of a ...

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Introduction Addressing the problem of suicidal thoughts and behavior (STB) in adolescents requires understanding the associated risk factors. While previous research has identified individual risk and protective factors associated with many adolescent social morbidities, modern machine learning approaches can help identify risk and protective factors that interact (group) to provide predictive power for STB. This study aims to develop a prediction algorithm for STB among adolescents using the risk and protective factor framework and social determinants of health. Methods The sample population consisted of more than 179,000 high school students living in Utah and participating in the Communities That Care (CTC) Youth Survey from 2011-2017. The dataset includes responses to 300+ questions from the CTC and 8000+ demographic factors from the American Census Survey for a total of 1.2 billion values. Machine learning techniques were employed to extract the survey questions that were best able to predict answers indicative of STB, using recent work in interpretable machine learning. Results Analysis showed strong predictive power, with the ability to predict individuals with STB with 91% accuracy. After extracting the top ten questions that most affected model predictions, questions fell into four main categories: familial life, drug consumption, demographics, and peer acceptance at school. Conclusions Modern machine learning approaches provide new methods for understanding the interaction between root causes and outcomes, such as STB. The model developed in this study showed significant improvement in predictive accuracy compared to previous research. Results indicate that certain risk and protective factors, such as adolescents being threatened or harassed through digital media or bullied at school, and exposure or involvement in serious arguments and yelling at home are the leading predictors of STB and can help narrow and reaffirm priority prevention programming and areas of focused policymaking.