Application of connectivity mapping in predictive toxicology based on gene-expression similarity.
Connectivity mapping is the process of establishing connections between different biological states using gene-expression profiles or signatures. There are a number of applications but in toxicology the most pertinent is for understanding mechanisms of toxicity. In its essence the process involves comparing a query gene signature generated as a result of exposure of a biological system to a chemical to those in a database that have been previously derived. In the ideal situation the query gene-expression signature is characteristic of the event and will be matched to similar events in the database. Key criteria are therefore the means of choosing the signature to be matched and the means by which the match is made. In this article we explore these concepts with examples applicable to toxicology.
Smalley
Joshua L
JL
Medical Research Council Toxicology Unit, University of Leicester, Systems Toxicology Group, Lancaster Road, Leicester, LE1 9HN, UK.
Gant
Timothy W
TW
Zhang
Shu-Dong
SD
D000818:Animals; D030541:Databases, Genetic; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000235:genetics; D012984:Software; D014116:Toxicology / Q000379:methods*
D011960:Receptors, Estrogen