Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus.

Like many viruses, Hepatitis C Virus (HCV) has a high mutation rate, which helps the virus adapt quickly, but mutations come with fitness costs. Fitness costs can be studied by different approaches, such as experimental or frequency-based approaches. The frequency-based approach is particularly useful to estimate in vivo fitness costs, but this approach works best with deep sequencing data from many hosts are. In this study, we applied the frequency-based approach to a large dataset of 195 patients and estimated the fitness costs of mutations at 7957 sites along the HCV genome. We used beta regression and random forest models to better understand how different factors influenced fitness costs. Our results revealed that costs of nonsynonymous mutations were three times higher than those of synonymous mutations, and mutations at nucleotides A or T had higher costs than those at C or G. Genome location had a modest effect, with lower costs for mutations in HVR1 and higher costs for mutations in Core and NS5B. Resistance mutations were, on average, costlier than other mutations. Our results show that in vivo fitness costs of mutations can be site and virus specific, reinforcing the utility of constructing in vivo fitness cost maps of viral genomes.

CpG-creating mutations are costly in many human viruses.

Mutations can occur throughout the virus genome and may be beneficial, neutral or deleterious. We are interested in mutations that yield a C next to a G, producing CpG sites. CpG sites are rare in eukaryotic and viral genomes. For the eukaryotes, it is thought that CpG sites are rare because they are prone to mutation when methylated. In viruses, we know less about why CpG sites are rare. A previous study in HIV suggested that CpG-creating transition mutations are more costly than similar non-CpG-creating mutations. To determine if this is the case in other viruses, we analyzed the allele frequencies of CpG-creating and non-CpG-creating mutations across various strains, subtypes, and genes of viruses using existing data obtained from Genbank, HIV Databases, and Virus Pathogen Resource. Our results suggest that CpG sites are indeed costly for most viruses. By understanding the cost of CpG sites, we can obtain further insights into the evolution and adaptation of viruses.

Preschoolers, parents, and teachers (PPT): a preventive intervention with an at risk population.

The importance of early intervention with children who are at risk for mental health problems is widely recognized. Relationships with significant adults (parents, other caregivers, and teachers) are critically important in young children's lives and can make a tremendous difference in the trajectory of a child's future. This study utilized a waiting-control group design to examine the effects on student behavior and parent stress of play-based interventions designed to improve the relationships between parents and their children (i.e., Filial Therapy), and teachers and their students (i.e., Kinder Training). To incorporate the benefits of group work, the eight-week intervention was delivered to parents in a small-group format. Teachers participated in a one-day group training with weekly coaching and dyadic consultation for on-going support. Results at post-intervention indicated that teachers perceived children in the intervention group to exhibit significantly less problem behavior than students in the waiting-control group. Although results suggest that the intervention had no demonstrable effect on parent stress, qualitative results indicate otherwise. Implications for practice and research are discussed.