Abstract

Antigenic characterization based on serological data, such as Hemagglutination Inhibition (HI) assay, is one of the routine procedures for influenza vaccine strain selection. In many cases, it would be impossible to measure all pairwise antigenic correlations between testing antigens and reference antisera in each individual experiment. Thus, we have to combine and integrate the HI tables from a number of individual experiments. Measurements from different experiments may be inconsistent due to different experimental conditions. Consequently we will observe a matrix with missing data and possibly inconsistent measurements. In this paper, we develop a new mathematical model, which we refer to as Joint Matrix Completion and Filtering, for HI data integration. In this approach, we simultaneously handle the incompleteness and uncertainty of observations by assuming that the underlying merged HI data matrix has low rank, as well as carefully modeling different levels of noises in each individual table. An efficient blockwise coordinate descent procedure is developed for optimization. The performance of our approach is validated on synthetic and real influenza datasets. The proposed joint matrix completion and filtering model can be adapted as a general model for biological data integration, targeting data noises and missing values within and across experiments.

Highlights

  • Influenza virus causes both seasonal epidemics and pandemics, and continues to present a threat to public health

  • For the simulated data and the influenza Hemagglutination Inhibition (HI) data of 2009 H1N1 an H3N2 used in this study, a 10-fold cross validation suggested a value of d between 3 and 20 for achieving low Root Mean Squared Error (RMSE)

  • Data Integration on Simulated HI Dataset To demonstrate the effectiveness of our model in influenza data integration, we performed Monte Carlo simulation using 100 randomly generated HI tables according to the joint model (1)

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Summary

Introduction

Influenza virus causes both seasonal epidemics and pandemics, and continues to present a threat to public health. Antigenic changes by drift or shift at influenza surface glycoproteins, especially hemagglutinin, changes its antigenic properties, and allows influenza virus to evade the accumulating herd immunity from influenza infection or vaccination [1,2]. Serological assays such as Hemagglutination Inhibition (HI) and Micro Neutralization (MN) are routine procedures used in antigenic variant identification [3]. A serological data can be viewed as an n|m matrix, where n and m are the numbers of antigens and antisera in the assays, respectively. The missing values are generally caused by the limitation of resources

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