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Novel reductive dehalogenases from the marine sponge associated bacterium Desulfoluna spongiiphila

Desulfoluna spongiiphila strain AA1 is an organohalide respiring bacterium, isolated from the marine sponge Aplysina aerophoba, that can use brominated and iodinated phenols, in addition to sulfate and thiosulfate as terminal electron acceptors. The …

Working toward precision medicine: Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges

Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of …

clubber: removing the bioinformatics bottleneck in big data analyses

With the advent of modern day high-throughput technologies, the bottleneck in biological discovery has shifted from the cost of doing experiments to that of analyzing results. clubber is our automated cluster-load balancing system developed for …

Common sequence variants affect molecular function more than rare variants?

Any two unrelated individuals differ by about 10,000 single amino acid variants (SAVs). Do these impact molecular function? Experimental answers cannot answer comprehensively, while state-of-the-art prediction methods can. We predicted the functional …

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative …

Performance of in silico tools for the evaluation of p16INK4a (CDKN2A) variants in CAGI

Correct phenotypic interpretation of variants of unknown significance for cancer-associated genes is a diagnostic challenge as genetic screenings gain in popularity in the next-generation sequencing era. The Critical Assessment of Genome …

Computational predictors fail to identify amino acid substitution effects at rheostat positions

Many computational approaches exist for predicting the effects of amino acid substitutions. Here, we considered whether the protein sequence position class - rheostat or toggle - affects these predictions. The classes are defined as follows: …

Computational prediction shines light on type III secretion origins

Type III secretion system is a key bacterial symbiosis and pathogenicity mechanism responsible for a variety of infectious diseases, ranging from food-borne illnesses to the bubonic plague. In many Gram-negative bacteria, the type III secretion …

Predicted Molecular Effects of Sequence Variants Link to System Level of Disease

Developments in experimental and computational biology are advancing our understanding of how protein sequence variation impacts molecular protein function. However, the leap from the micro level of molecular function to the macro level of the whole …

Protein function in precision medicine: deep understanding with machine learning

Precision medicine and personalized health efforts propose leveraging complex molecular, medical and family history, along with other types of personal data toward better life. We argue that this ambitious objective will require advanced and …