Optimization of Random Forest Based Methods Applying the Genetic Algorithms

In this century access to large and complex datasets is much easier. These datasets are large in dimension and volume, and researchers are interested in methods that are able to handle this type of data and at the same time produce accurate results. Machine learning methods are particularly efficient for this type of data, where the emphasis is on data analysis, and not on fitting a statistical model. A very popular method from this group is Random Forests which have been applied in different areas of study on two types of problems: classification and regression. The former is more popular, while the latter can be applied for data analysis. Moreover, many efficient techniques for missing value imputation were added to Random Forest over time. One of these methods which can handle all types of variables is MissForest. There are several studies that applied different approaches to improve the performance of classification type of Random Forests, but there are not many studies available for regression type. In the present study, it is evaluated if the performance of regression type of Random Forests and MissForests could be improved by applying Genetic Algorithms as an optimization method. The experiments were conducted on five datasets to minimize the mean square error (MSE) of the Random Forest and imputation errors of the MissForest. The results showed the superiority of the proposed method in comparison to the classical Random Forest methods

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.</p

Enhancing anti-viral neutralization response to immunization with HIV-1 envelope glycoprotein immunogens

Abstract An effective human immunodeficiency virus type I (HIV-1) vaccine that robustly elicits broadly neutralizing antibodies (bnAbs) against HIV-1 envelope glycoproteins (Envs) to block viral entry is still not available. Thus, identifying triggers for elicitation of different types of anti-HIV-1 Env antibodies by vaccination could provide further guidance for immunogen design and vaccine development. Here, we studied the immune response to HIV-1 Env immunogens in rabbits. We show that sequential immunizations with conformation-specific Env immunogens can elicit low titer but broad neutralization responses against heterologous, neutralization-resistant (tier 2/3) transmitted/founder (T/F) HIV-1 strains. More importantly, an mRNA vaccine candidate that could mediate the presentation of a cytoplasmic tail-deleted (ΔCT) HIV-1AD8 Env immunogen on virus-like particles significantly increased the neutralization response. This strategy shifted the type of elicited antibodies, decreasing the level of binding to soluble Envs while significantly increasing their overall viral neutralization activity. The breadth and potency of neutralizing response against heterologous, T/F HIV-1 strains significantly increased in a subset of rabbits. Efficient neutralization activity was associated with high cellular immune responses specific to HIV-1 Envs. These results help to understand the immune response to different immunization schemes and will allow developing new approaches to selectively manipulate the type of humoral immune response by specific vaccination