Analysis of Chemical and Biological Features Yields Mechanistic Insights into Drug Side Effects

被引:44
作者
Duran-Frigola, Miquel [1 ]
Aloy, Patrick [1 ,2 ]
机构
[1] Inst Res Biomed IRB Barcelona, Joint IRB BSC Program Computat Biol, Barcelona 08028, Spain
[2] ICREA, Barcelona 08010, Spain
来源
CHEMISTRY & BIOLOGY | 2013年 / 20卷 / 04期
关键词
PHARMACOLOGY; PREDICTION;
D O I
10.1016/j.chembiol.2013.03.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Side effects (SEs) are the unintended consequence of therapeutic treatments, but they can also be seen as valuable readouts of drug effects, resulting from the perturbation of biological systems by chemical compounds. Unfortunately, biology and chemistry are often considered separately, leading to incomplete models unable to provide a unified view of SEs. Here, we investigate the molecular bases of over 1,600 SEs by navigating both chemical and biological spaces. We identified characteristic molecular traits for 1,162 SEs, 38% of which can be explained using solely biological arguments, and only 6% are exclusively associated with the chemistry of the compounds, implying that the drug action is somewhat unspecific. Overall, we provide mechanistic insights for most SEs and emphasize the need to blend biology and chemistry to surpass intricate phenomena not captured in the molecular biology view.
引用
收藏
页码:594 / 603
页数:10
相关论文
共 49 条
[1]   Improved scoring of functional groups from gene expression data by decorrelating GO graph structure [J].
Alexa, Adrian ;
Rahnenfuehrer, Joerg ;
Lengauer, Thomas .
BIOINFORMATICS, 2006, 22 (13) :1600-1607
[2]  
ARNOLD W N, 1991, Eye (London), V5, P503
[3]   Automatic Filtering and Substantiation of Drug Safety Signals [J].
Bauer-Mehren, Anna ;
van Mullingen, Erik M. ;
Avillach, Paul ;
del Carmen Carrascosa, Maria ;
Garcia-Serna, Ricard ;
Pinero, Janet ;
Singh, Bharat ;
Lopes, Pedro ;
Oliveira, Jose L. ;
Diallo, Gayo ;
Helgee, Ernst Ahlberg ;
Boyer, Scott ;
Mestres, Jordi ;
Sanz, Ferran ;
Kors, Jan A. ;
Furlong, Laura I. .
PLOS COMPUTATIONAL BIOLOGY, 2012, 8 (04)
[4]   Pharmacogenomics of adverse drug reactions: practical applications and perspectives [J].
Becquemont, Laurent .
PHARMACOGENOMICS, 2009, 10 (06) :961-969
[5]   The properties of known drugs .1. Molecular frameworks [J].
Bemis, GW ;
Murcko, MA .
JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (15) :2887-2893
[6]   Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure [J].
Bender, Andreas ;
Scheiber, Josef ;
Glick, Meir ;
Davies, John W. ;
Azzaoui, Kamal ;
Hamon, Jacques ;
Urban, Laszlo ;
Whitebread, Steven ;
Jenkins, Jeremy L. .
CHEMMEDCHEM, 2007, 2 (06) :861-873
[7]   Role of systems pharmacology in understanding drug adverse events [J].
Berger, Seth I. ;
Iyengar, Ravi .
WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE, 2011, 3 (02) :129-135
[8]   Relevance of animal models to human tardive dyskinesia [J].
Blanchet, Pierre J. ;
Parent, Marie-Therese ;
Rompre, Pierre H. ;
Levesque, Daniel .
BEHAVIORAL AND BRAIN FUNCTIONS, 2012, 8
[9]   Predicting Adverse Drug Events Using Pharmacological Network Models [J].
Cami, Aurel ;
Arnold, Alana ;
Manzi, Shannon ;
Reis, Ben .
SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (114)
[10]   Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance [J].
Clayton-Smith, Jill ;
Walters, Sarah ;
Hobson, Emma ;
Burkitt-Wright, Emma ;
Smith, Rupert ;
Toutain, Annick ;
Amiel, Jeanne ;
Lyonnet, Stanislas ;
Mansour, Sahar ;
Fitzpatrick, David ;
Ciccone, Roberto ;
Ricca, Ivana ;
Zuffardi, Orsetta ;
Donnai, Dian .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2009, 17 (04) :434-443