Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in SARS-CoV-2 and Its Variants (preprint)

Background: Host response is critical to the onset, progression, and outcome of viral infections. Since viruses hijack the host cellular metabolism for their replications, we hypothesized that restoring host cell metabolism can efficiently reduce viral production. Here, we present a viral-host Metabolic Modeling (vhMM) method to systematically evaluate the disturbances in host metabolism in viral infection and computationally identify targets for modulation by integrating genome-wide precision metabolic modeling and cheminformatics. Results: In SARS-CoV-2 infections, we identified consistent changes in host metabolism and gene and endogenous metabolite targets between the original SARS-COV-2 and different variants (Alpha, Delta, and Omicron). Among six compounds predicted for repurposing, methotrexate, cinnamaldehyde, and deferiprone were tested in vitro and effective in inhibiting viral production with IC50 less than 4uM. Further, an analysis of real-world patient data showed that cinnamon usage significantly reduced the SARS-CoV-2 infection rate with an odds ratio of 0.65 [95%CI: 0.55~0.75]. Conclusions: These results demonstrated that vhMM is an efficient method for predicting targets and drugs for viral infections.

Forecasting unemployment using Internet search data via PRISM (preprint)

Big data generated from the Internet offer great potential for predictive analysis. Here we focus on using online users' Internet search data to forecast unemployment initial claims weeks into the future, which provides timely insights into the direction of the economy. To this end, we present a novel method PRISM (Penalized Regression with Inferred Seasonality Module), which uses publicly available online search data from Google. PRISM is a semi-parametric method, motivated by a general state-space formulation, and employs nonparametric seasonal decomposition and penalized regression. For forecasting unemployment initial claims, PRISM outperforms all previously available methods, including forecasting during the 2008-2009 financial crisis period and near-future forecasting during the COVID-19 pandemic period, when unemployment initial claims both rose rapidly. The timely and accurate unemployment forecasts by PRISM could aid government agencies and financial institutions to assess the economic trend and make well-informed decisions, especially in the face of economic turbulence.