著者

山西 芳裕 Yoshihiro Yamanishi 九州大学生体防御医学研究所高等研究院 Medical Institute of Bioregulation and Institute for Advanced Study Kyushu University

出版者

人工知能学会 ; 2014-

雑誌

人工知能 = journal of the Japanese Society for Artificial Intelligence (ISSN:21882266)

巻号頁・発行日

vol.30, no.2, pp.224-229, 2015-03-01

著者

Yuto Amano Hiroshi Honda Ryusuke Sawada Yuko Nukada Masayuki Yamane Naohiro Ikeda Osamu Morita Yoshihiro Yamanishi

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.45, no.3, pp.137-149, 2020 (Released:2020-03-06)

参考文献数

47

被引用文献数

5

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In silico models for predicting chemical-induced side effects have become increasingly important for the development of pharmaceuticals and functional food products. However, existing predictive models have difficulty in estimating the mechanisms of side effects in terms of molecular targets or they do not cover the wide range of pharmacological targets. In the present study, we constructed novel in silico models to predict chemical-induced side effects and estimate the underlying mechanisms with high general versatility by integrating the comprehensive prediction of potential chemical-protein interactions (CPIs) with machine learning. First, the potential CPIs were comprehensively estimated by chemometrics based on the known CPI data (1,179,848 interactions involving 3,905 proteins and 824,143 chemicals). Second, the predictive models for 61 side effects in the cardiovascular system (CVS), gastrointestinal system (GIS), and central nervous system (CNS) were constructed by sparsity-induced classifiers based on the known and potential CPI data. The cross validation experiments showed that the proposed CPI-based models had a higher or comparable performance than the traditional chemical structure-based models. Moreover, our enrichment analysis indicated that the highly weighted proteins derived from predictive models could be involved in the corresponding functions of the side effects. For example, in CVS, the carcinogenesis-related pathways (e.g., prostate cancer, PI3K-Akt signal pathway), which were recently reported to be involved in cardiovascular side effects, were enriched. Therefore, our predictive models are biologically valid and would be useful for predicting side effects and novel potential underlying mechanisms of chemical-induced side effects.

著者

Yoshihiro Yamanishi Masumi Itoh Minoru Kanehisa

出版者

Japanese Society for Bioinformatics

雑誌

Genome Informatics (ISSN:09199454)

巻号頁・発行日

vol.13, pp.61-70, 2002 (Released:2011-07-11)

参考文献数

12

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In recent years, the analysis of orthologous genes based on phylogenetic profiles has received popularity in bioinfomatics. We propose a new method to extract organism groups and their hierarchy from phylogenetic profiles using the independent component analysis (ICA). The method involves first finding independent axes in the projected space from the multivariate data matrix representing phylogenetic profiles for a number of orthologous genes. Then the extracted axes are correlated with major organism groups, according to the extent of affiliaion of axes scores for all the genes to specific organisms. The ICA was applied to the phylogenetic profiles created for 2875 orthologs in 77 organisms by using the KEGG/GENES database. The 9 extracted components out of 18 predefined components well represented the organism groups as categorized in KEGG. Furthermore, we performed the cluster analysis and obtained the hierarchy of organism groups.