{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:55:17Z","timestamp":1780764917746,"version":"3.54.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1490,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system\u2013wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs.<\/jats:p><jats:p>Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug\u2013targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles.<\/jats:p><jats:p>Supplementary information: Datasets and all results are available at http:\/\/web.kuicr.kyoto-u.ac.jp\/supp\/smizutan\/target-effect\/.<\/jats:p><jats:p>Availability: Software is available at the above supplementary website.<\/jats:p><jats:p>Contact: \u00a0yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts383","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T20:35:22Z","timestamp":1347050122000},"page":"i522-i528","source":"Crossref","is-referenced-by-count":196,"title":["Relating drug\u2013protein interaction network with drug side effects"],"prefix":"10.1093","volume":"28","author":[{"given":"Sayaka","family":"Mizutani","sequence":"first","affiliation":[{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Pauwels","sequence":"additional","affiliation":[{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"},{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"},{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Stoven","sequence":"additional","affiliation":[{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"},{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"},{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Goto","sequence":"additional","affiliation":[{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Yamanishi","sequence":"additional","affiliation":[{"name":"1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan, 2Mines ParisTech, Centre for Computational Biology, 35 rue Saint-Honor\u00e9, F-77305 Fontainebleau Cedex, France, 3Institut Curie, F-75248, Paris, France, 4INSERM U900, F-75248 Paris, France and 5Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,3]]},"reference":[{"key":"2023012513070254500_B1","volume-title":"Side Effects of Drugs 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