Antigenicity prediction and vaccine recommendation of human influenza virus A (H3N2) using convolutional neural networks.

The rapid evolution of influenza A viruses poses a great challenge to vaccine development. Analytical and machine learning models have been applied to facilitate the process of antigenicity determination. In this study, we designed deep convolutional neural networks (CNNs) to predict Influenza antigenicity. Our model is the first that systematically analyzed 566 amino acid properties and 141 amino acid substitution matrices for their predictability. We then optimized the structure of the CNNs using particle swarm optimization. The optimal neural networks outperform other predictive models with a blind validation accuracy of 95.8%. Further, we applied our model to vaccine recommendations in the period 1997 to 2011 and contrasted the performance of previous vaccine recommendations using traditional experimental approaches. The results show that our model outperforms the WHO recommendation and other existing models and could potentially improve the vaccine recommendation process. Our results show that WHO often selects virus strains with small variation from year to year and learns slowly and recovers once coverage dips very low. In contrast, the influenza strains selected via our CNN model can differ quite drastically from year to year and exhibit consistently good coverage. In summary, we have designed a comprehensive computational pipeline for optimizing a CNN in the modeling of Influenza A antigenicity and vaccine recommendation. It is more cost and time-effective when compared to traditional hemagglutination inhibition assay analysis. The modeling framework is flexible and can be adopted to study other type of viruses.

Investigating a Needle-Based Epidural Procedure in Obstetric Anesthesia.

This study investigates the safety and efficacy of a large-dose, needle-based epidural technique in obstetric anesthesia. The technique differs from a standard, catheter-based approach in that the anesthetic dose is administered through an epidural needle prior to insertion of the epidural catheter. Using a data-driven informatics and machine learning approach, our findings show that the needle-based technique is faster and more dose-effective in achieving sensory level. We also find that injecting large doses in the epidural space through the epidural needle is safe, with complication rates similar to those reported in published literature for catheter-based technique. Further, machine learning reveals that if the needle dose is kept under 18 ml, the resulting hypotension rate will be significantly lower than published results. The machine learning framework can predict the incidence of hypotension with 85% accuracy. The findings from this investigation facilitate delivery improvement and establish an improved clinical practice guideline for training and for dissemination of safe practice.

Omic personality: implications of stable transcript and methylation profiles for personalized medicine.

BACKGROUND: Personalized medicine is predicated on the notion that individual biochemical and genomic profiles are relatively constant in times of good health and to some extent predictive of disease or therapeutic response. We report a pilot study quantifying gene expression and methylation profile consistency over time, addressing the reasons for individual uniqueness, and its relation to N = 1 phenotypes. METHODS: Whole blood samples from four African American women, four Caucasian women, and four Caucasian men drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNA-Seq, miRNA-Seq, and Illumina Methylation 450 K arrays. Standard regression approaches were used to evaluate the proportion of variance for each type of omic measure among individuals, and to quantify correlations among measures and with clinical attributes related to wellness. RESULTS: Longitudinal omic profiles were in general highly consistent over time, with an average of 67 % variance in transcript abundance, 42 % in CpG methylation level (but 88 % for the most differentiated CpG per gene), and 50 % in miRNA abundance among individuals, which are all comparable to 74 % variance among individuals for 74 clinical traits. One third of the variance could be attributed to differential blood cell type abundance, which was also fairly stable over time, and a lesser amount to expression quantitative trait loci (eQTL) effects. Seven conserved axes of covariance that capture diverse aspects of immune function explained over half of the variance. These axes also explained a considerable proportion of individually extreme transcript abundance, namely approximately 100 genes that were significantly up-regulated or down-regulated in each person and were in some cases enriched for relevant gene activities that plausibly associate with clinical attributes. A similar fraction of genes had individually divergent methylation levels, but these did not overlap with the transcripts, and fewer than 20 % of genes had significantly correlated methylation and gene expression. CONCLUSIONS: People express an "omic personality" consisting of peripheral blood transcriptional and epigenetic profiles that are constant over the course of a year and reflect various types of immune activity. Baseline genomic profiles can provide a window into the molecular basis of traits that might be useful for explaining medical conditions or guiding personalized health decisions.