Genetic determination of regional connectivity in modelling the spread of COVID-19 outbreak for more efficient mitigation strategies.

For the COVID-19 pandemic, viral transmission has been documented in many historical and geographical contexts. Nevertheless, few studies have explicitly modeled the spatiotemporal flow based on genetic sequences, to develop mitigation strategies. Additionally, thousands of SARS-CoV-2 genomes have been sequenced with associated records, potentially providing a rich source for such spatiotemporal analysis, an unprecedented amount during a single outbreak. Here, in a case study of seven states, we model the first wave of the outbreak by determining regional connectivity from phylogenetic sequence information (i.e. "genetic connectivity"), in addition to traditional epidemiologic and demographic parameters. Our study shows nearly all of the initial outbreak can be traced to a few lineages, rather than disconnected outbreaks, indicative of a mostly continuous initial viral flow. While the geographic distance from hotspots is initially important in the modeling, genetic connectivity becomes increasingly significant later in the first wave. Moreover, our model predicts that isolated local strategies (e.g. relying on herd immunity) can negatively impact neighboring regions, suggesting more efficient mitigation is possible with unified, cross-border interventions. Finally, our results suggest that a few targeted interventions based on connectivity can have an effect similar to that of an overall lockdown. They also suggest that while successful lockdowns are very effective in mitigating an outbreak, less disciplined lockdowns quickly decrease in effectiveness. Our study provides a framework for combining phylodynamic and computational methods to identify targeted interventions.

Insights from incorporating quantum computing into drug design workflows.

MOTIVATION: While many quantum computing (QC) methods promise theoretical advantages over classical counterparts, quantum hardware remains limited. Exploiting near-term QC in computer-aided drug design (CADD) thus requires judicious partitioning between classical and quantum calculations. RESULTS: We present HypaCADD, a hybrid classical-quantum workflow for finding ligands binding to proteins, while accounting for genetic mutations. We explicitly identify modules of our drug-design workflow currently amenable to replacement by QC: non-intuitively, we identify the mutation-impact predictor as the best candidate. HypaCADD thus combines classical docking and molecular dynamics with quantum machine learning (QML) to infer the impact of mutations. We present a case study with the coronavirus (SARS-CoV-2) protease and associated mutants. We map a classical machine-learning module onto QC, using a neural network constructed from qubit-rotation gates. We have implemented this in simulation and on two commercial quantum computers. We find that the QML models can perform on par with, if not better than, classical baselines. In summary, HypaCADD offers a successful strategy for leveraging QC for CADD. AVAILABILITY AND IMPLEMENTATION: Jupyter Notebooks with Python code are freely available for academic use on GitHub: https://www.github.com/hypahub/hypacadd_notebook. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.