Da Xu1, Hanxiao Xu1, Yusen Zhang2, Mingyi Wang3, Wei Chen1, Rui Gao4. 1. School of Mathematics and Statistics, Shandong University, Weihai, 264209, China. 2. School of Mathematics and Statistics, Shandong University, Weihai, 264209, China. zhangys@sdu.edu.cn. 3. Department of Central Lab, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China. wangmingyi1973@outlook.com. 4. School of Control Science and Engineering, Shandong University, Jinan, 250061, China.
Abstract
BACKGROUND: Microbes are closely related to human health and diseases. Identification of disease-related microbes is of great significance for revealing the pathological mechanism of human diseases and understanding the interaction mechanisms between microbes and humans, which is also useful for the prevention, diagnosis and treatment of human diseases. Considering the known disease-related microbes are still insufficient, it is necessary to develop effective computational methods and reduce the time and cost of biological experiments. METHODS: In this work, we developed a novel computational method called MDAKRLS to discover potential microbe-disease associations (MDAs) based on the Kronecker regularized least squares. Specifically, we introduced the Hamming interaction profile similarity to measure the similarities of microbes and diseases besides Gaussian interaction profile kernel similarity. In addition, we introduced the Kronecker product to construct two kinds of Kronecker similarities between microbe-disease pairs. Then, we designed the Kronecker regularized least squares with different Kronecker similarities to obtain prediction scores, respectively, and calculated the final prediction scores by integrating the contributions of different similarities. RESULTS: The AUCs value of global leave-one-out cross-validation and 5-fold cross-validation achieved by MDAKRLS were 0.9327 and 0.9023 ± 0.0015, which were significantly higher than five state-of-the-art methods used for comparison. Comparison results demonstrate that MDAKRLS has faster computing speed under two kinds of frameworks. In addition, case studies of inflammatory bowel disease (IBD) and asthma further showed 19 (IBD), 19 (asthma) of the top 20 prediction disease-related microbes could be verified by previously published biological or medical literature. CONCLUSIONS: All the evaluation results adequately demonstrated that MDAKRLS has an effective and reliable prediction performance. It may be a useful tool to seek disease-related new microbes and help biomedical researchers to carry out follow-up studies.
BACKGROUND: Microbes are closely related to human health and diseases. Identification of disease-related microbes is of great significance for revealing the pathological mechanism of human diseases and understanding the interaction mechanisms between microbes and humans, which is also useful for the prevention, diagnosis and treatment of human diseases. Considering the known disease-related microbes are still insufficient, it is necessary to develop effective computational methods and reduce the time and cost of biological experiments. METHODS: In this work, we developed a novel computational method called MDAKRLS to discover potential microbe-disease associations (MDAs) based on the Kronecker regularized least squares. Specifically, we introduced the Hamming interaction profile similarity to measure the similarities of microbes and diseases besides Gaussian interaction profile kernel similarity. In addition, we introduced the Kronecker product to construct two kinds of Kronecker similarities between microbe-disease pairs. Then, we designed the Kronecker regularized least squares with different Kronecker similarities to obtain prediction scores, respectively, and calculated the final prediction scores by integrating the contributions of different similarities. RESULTS: The AUCs value of global leave-one-out cross-validation and 5-fold cross-validation achieved by MDAKRLS were 0.9327 and 0.9023 ± 0.0015, which were significantly higher than five state-of-the-art methods used for comparison. Comparison results demonstrate that MDAKRLS has faster computing speed under two kinds of frameworks. In addition, case studies of inflammatory bowel disease (IBD) and asthma further showed 19 (IBD), 19 (asthma) of the top 20 prediction disease-related microbes could be verified by previously published biological or medical literature. CONCLUSIONS: All the evaluation results adequately demonstrated that MDAKRLS has an effective and reliable prediction performance. It may be a useful tool to seek disease-related new microbes and help biomedical researchers to carry out follow-up studies.
Entities:
Keywords:
Association prediction; Disease; Kronecker regularized least squares; Machine learning; Microbe
Authors: H Sokol; P Seksik; J P Furet; O Firmesse; I Nion-Larmurier; L Beaugerie; J Cosnes; G Corthier; P Marteau; J Doré Journal: Inflamm Bowel Dis Date: 2009-08 Impact factor: 5.325
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