Simple SummaryThe H9N2 avian influenza virus has spread to the whole world and become one of the dominant subtype influenza viruses in chickens in China. H9N2 virus could not only result in great economic losses by reducing egg production but also serve as a gene vector to provide its gene segments to other emerging severe influenza A viruses to cause higher mortality and more serious consequences. Thus, developing models to predict H9N2 status should be given priority. Our main aim was to use the machine learning method (XGBoost classification algorithm) and regular production data (laying rate and mortality) to predict the occurrence and development of H9N2 in laying hen houses and evaluate their performance in disease prediction. Additionally, we assessed the working ability of the framework with different time frames to predict H9N2 status in advance within a 3-day period. We found that this framework could work well in prediction with high accuracy and sensitivity, and with more information introduced into the model, more “don’t care values” would be added into datasets to affect model performance by forming attribute noise. Besides, our study recommended efficient frameworks and models for H9N2 status prediction and provided practical potential uses in the livestock and poultry industry.AbstractThe H9N2 avian influenza virus has become one of the dominant subtypes of avian influenza virus in poultry and has been significantly harmful to chickens in China, with great economic losses in terms of reduced egg production or high mortality by co-infection with other pathogens. A prediction of H9N2 status based on easily available production data with high accuracy would be important and essential to prevent and control H9N2 outbreaks in advance. This study developed a machine learning framework based on the XGBoost classification algorithm using 3 months’ laying rates and mortalities collected from three H9N2-infected laying hen houses with complete onset cycles. A framework was developed to automatically predict the H9N2 status of individual house for future 3 days (H9N2 status + 0, H9N2 status + 1, H9N2 status + 2) with five time frames (day + 0, day − 1, day − 2, day − 3, day − 4). It had been proven that a high accuracy rate > 90%, a recall rate > 90%, a precision rate of >80%, and an area under the curve of the receiver operator characteristic ≥ 0.85 could be achieved with the prediction models. Models with day + 0 and day − 1 were highly recommended to predict H9N2 status + 0 and H9N2 status + 1 for the direct or auxiliary monitoring of its occurrence and development. Such a framework could provide new insights into predicting H9N2 outbreaks, and other practical potential applications to assist in disease monitor were also considerable.