Keyword Description

Drug ID: Drugs used in the web server are numbered as TGP. Details information of these drugs were placed in download page.
Score: Score value indicates the similarity of mechanism between the drugs and query signature. A high positive score means more similar between the drugs and query signature.
P-value: The P-value reflect the significance of the score.
instance: A treatment and control pair, generated by sorting all probes in the array by their fold-changes.
signature: A set of probes.

Example

To exemplify the application that allows the use of LTMap to identify potential toxicities of new chemical entities, we used the liver transcriptomics data for compound nafenopin retrieved from Drugmatrix to compile a query gene signature.

Step 1: "query signature" is accepted in different formats:

  • The list of gene probes could be separated by comma, space or tab.

  • After submitting probe sets, users can choose different time points, dosage and organism as needed. LTMap will automatically search for compounds that have coordinated changes in gene expression.

    Figure 1: Probe sets of up- or down- regulated were the top20 probes.



    Step 2: In the result page, a list of drugs with scores, p-values and more descriptions will be presented. Users can filter the drugs by the values of any column fields.

    Figure 2: Result table as shown above



    Step 3: We first sort the table by their scores in order to identify compounds that induce toxicity through similar mechanisms.

    Figure 3: Result table as shown above sorted by scores



    Step 4: Click the right icon buttonbushes, users can visualize detail information of corresponding gene expression profiles of the selected drugs.

    Figure 4: Corresponding gene expression profiles of the selected drugs



    Nafenopin was reported as an activator of PPARĪ±, which is not included in the LTMap data set. For the nafenopin drugs query signature, by setting search criteria of experimental design, time Point and dose, the identified stronger positive connections incluede fenofibrate, benzbromarone, gemfibrozil, clofibrozil. These compounds all are are PPARĪ± agonists. Peroxisome proliferators produce oxidative stress and hepatotoxicity in rats and represent an important group of hepatic carcinogens in rodents. This result clearly indicates the potential of this tool to detect toxic changes in the liver.

    How can I cite LTMap?

    We hope all articles who used the result of LTMap can cite the website address below:

    LTMap: a web server for assessing the potential liver toxicity by genome-wide transcriptional expression data.