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The use of viral sequence data to inform public health intervention has become increasingly common in the realm of epidemiology. Such methods typically utilize multiple sequence alignments and phylogenies estimated from the sequence data. Like all estimation techniques, they are error prone, yet the impacts of such imperfections on downstream epidemiological inferences are poorly understood. To address this, we executed multiple commonly used viral phylogenetic analysis workflows on simulated viral sequence data, modeling Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and Ebolavirus, and we computed multiple methods of accuracy, motivated by transmission-clustering techniques. For multiple sequence alignment, MAFFT consistently outperformed MUSCLE and Clustal Omega, in both accuracy and runtime. For phylogenetic inference, FastTree 2, IQ-TREE, RAxML-NG, and PhyML had similar topological accuracies, but branch lengths and pairwise distances were consistently most accurate in phylogenies inferred by RAxML-NG. However, FastTree 2 was the fastest, by orders of magnitude, and when the other tools were used to optimize branch lengths along a fixed FastTree 2 topology, the resulting phylogenies had accuracies that were indistinguishable from their original counterparts, but with a fraction of the runtime. 

Glioblastoma (GBM) is one of the most aggressive forms of adult brain cancers and is highly resistant to treatment, with a median survival of 12–18 months after diagnosis. The poor survival is due to its infiltrative pattern of invasion into the normal brain parenchyma, the diffuse nature of its growth, and its ability to quickly grow, spread, and relapse. Temozolomide is a well-known FDA-approved alkylating chemotherapy agent used for the treatment of high-grade malignant gliomas, and it has been shown to improve overall survival. However, in most cases, the tumor relapses. In recent years, CAP has been used as an emerging technology for cancer therapy. The purpose of this study was to implement a combination therapy of CAP and TMZ to enhance the effect of TMZ and apparently sensitize GBMs. In vitro evaluations in TMZ-sensitive and resistant GBM cell lines established a CAP chemotherapy enhancement and potential sensitization effect across various ranges of CAP jet application. This was further supported with in vivo findings demonstrating that a single CAP jet applied non-invasively through the skull potentially sensitizes GBM to subsequent treatment with TMZ. Gene functional enrichment analysis further demonstrated that co-treatment with CAP and TMZ resulted in a downregulation of cell cycle pathway genes. These observations indicate that CAP can be potentially useful in sensitizing GBM to chemotherapy and for the treatment of glioblastoma as a non-invasive translational therapy.