MANTRA2.0
前言
MANTRA 咒语的意思,该software是在2010年意大利的团队发表在PNAS上的一款构造drug Network的软件。之后,同团队,在2014年晋级2.0版。
这几天一直在探索Network的方法,无意碰到这篇文章,就对文中的方法和该软件很好奇。但是,搜索全网竟然一篇对该软件的解读都没有,所以准备写个引导,以便后来的小伙伴参考。
网站
里面该软件的tutorial 和 workflow
https://mantra.tigem.it/About/AboutTutorial.aspx
MANTRA 2.0 is a collaborative resource for elucidating drug MoA and for drug repurposing. The network framework makes it easy to discover unexpected relationships among drugs, genes and diseases. The possibility of uploading and sharing user’s data allows for the growth of the network, thus making MANTRA 2.0 an ever-growing collaborative resource for drug discovery.
算法
Drug network and Communities
- For each compound, we considered all the transcriptional responses following treatments, across different cell lines and/or at different concentrations. Each transcriptional response was represented as a list of genes ranked according to their differential expression.
- We then computed a single “synthetic” ranked list of genes, the Prototype Ranked List (PRL), by merging all the ranked lists referring to the same compound.
In order to equally weight the contribution of each of the cell lines to the drug PRL, rank merging was achieved with a procedure based on a hierarchical majority-voting scheme, where genes consistently overexpressed/down-regulated across the ranked lists are moved at the top/bottom of the PRL.
- The PRL thus captures the consensus transcriptional response of a compound across different experimental settings, consistently reducing nonrelevant effects due to toxicity, dosage, and cell line.
Tips: PRL generation
Built a PRL for each drug by aggregating all the ranked lists that have been obtained by treating cells with that drug (i.e., on different cell lines, with different concentrations, etc.).
methods: a measure of the distance between two ranked lists (Spearman’s Foo- trule);
a method to merge two or more ranked lists (the Borda Merging Method);
and an algorithm to obtain a single ranked list from a set of them in a hierarchical way (the Kruskal Algorithm).
结果
Constrcted a "drug network" of 1,302 nodes(drugs) and 41,047 edges (indicating similarities between pair of drugs).
参考文献:
- Iorio F, Bosotti R, Scacheri E, Belcastro V, Mithbaokar P, Ferriero R, Murino L, Tagliaferri R, Brunetti-Pierri N, Isacchi A, di Bernardo D. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc Natl Acad Sci U S A, 2010 August 17; 107: 14621-14626.
- Carrella D, Napolitano F, Rispoli R, Miglietta M, Carissimo A, Cutillo L, Sirci F, Gregoretti F, di Bernardo D. Mantra 2.0: an online collaborative resource for drug mode of action and repurposing by network analysis.Bioinformatics (2014) 30 (12): 1787-1788.