Supertree methods construct trees on a set of taxa (species) combining many smaller trees on the overlapping subsets of the entire set of taxa. A ‘quartet’ is an unrooted tree over taxa, hence the quartet-based supertree methods combine many -taxon unrooted trees into a single and coherent tree over the complete set of taxa. Quartet-based phylogeny reconstruction methods have been receiving considerable attentions in the recent years. An accurate and efficient quartet-based method might be competitive with the current best phylogenetic tree reconstruction methods (such as maximum likelihood or Bayesian MCMC analyses), without being as computationally intensive. In this paper, we present a novel and highly accurate quartet-based phylogenetic tree reconstruction method. We performed an extensive experimental study to evaluate the accuracy and scalability of our approach on both simulated and biological datasets.

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Interpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variations on protein structure and function being especially challenging. Here we characterize the three-dimensional (3D) amino acid positions affected in pathogenic and population variants from 1,330 disease-associated genes using over 14,000 experimentally solved human protein structures. By measuring the statistical burden of variations (i.e., point mutations) from all genes on 40 3D protein features, accounting for the structural, chemical, and functional context of the variations’ positions, we identify features that are generally associated with pathogenic and population missense variants. We then perform the same amino acid-level analysis individually for 24 protein functional classes, which reveals unique characteristics of the positions of the altered amino acids: We observe up to 46% divergence of the class-specific features from the general characteristics obtained by the analysis on all genes, which is consistent with the structural diversity of essential regions across different protein classes. We demonstrate that the function-specific 3D features of the variants match the readouts of mutagenesis experiments for BRCA1 and PTEN, and positively correlate with an independent set of clinically interpreted pathogenic and benign missense variants. Finally, we make our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step toward translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the variants’ pathogenicity in terms of the perturbed molecular mechanisms.

The coronavirus disease 2019 (COVID-19) has resulted in an ongoing pandemic worldwide. Countries have adopted non-pharmaceutical interventions (NPI) to slow down the spread. This study proposes an agent-based model that simulates the spread of COVID-19 among the inhabitants of a city. The agent-based model can be accommodated for any location by integrating parameters specific to the city. The simulation gives the number of total COVID-19 cases. Considering each person as an agent susceptible to COVID-19, the model causes infected individuals to transmit the disease via various actions performed every hour. The model is validated by comparing the simulation to the real data of Ford County, KS, USA. Different interventions, including contact tracing, are applied on a scaled-down version of New York City, USA, and the parameters that lead to a controlled epidemic are determined. Our experiments suggest that contact tracing via smartphones with more than 60% of the population owning a smartphone combined with city-wide lockdown results in the effective reproduction number ( R t ) to fall below 1 within 3 weeks of intervention. For 75% or more smartphone users, new infections are eliminated, and the spread is contained within 3 months of intervention. Contact tracing accompanied with early lockdown can suppress the epidemic growth of COVID-19 completely with sufficient smartphone owners. In places where it is difficult to ensure a high percentage of smartphone ownership, tracing only emergency service providers during a lockdown can go a long way to contain the spread. Supplementary Information The online version contains supplementary material available at (10.1007/s12559-020-09801-w)

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