Li14, BMC Medical Genomics, predict disease genes using weighted tissue-specific networks

Li et al. BMC Medical Genomics 2014, 7(Suppl 2):S4 Prediction of disease-related genes based on weighted tissue-specific networks by using DNA methylation

http://www.biomedcentral.com/1755-8794/7/S2/S4

Min Li1, Jiayi Zhang1, Qing Liu1, Jianxin Wang1*, Fang-Xiang Wu1,2*

From IEEE International Conference on Bioinformatics and Biomedicine (BIBM 2013)

 "Considering the fact that the majority of genetic disorders tend to manifest only in a single or a few

tissues, we constructed tissue-specific networks (TSN) by integrating PIN and tissue-specific data." Qin: The observation is true, but it does not mean disease genes are only found in tissues with clinic phenotypes. These tissues show phenotypes only probably because the disease-causing genes play limiting roles in this tissues. 

 "In this paper, we treated known aberrant methylation genes as seed nodes and set initial quantity value with the use of the seed set, which will enhance the importance of seed nodes in network and solve defects of initial PageRank algorithm. The aberrant methylation data related to specific diseases in PubMeth database [44] were used in this paper." 

Li14 used page-rank method to predict disease genes, but seemed to modify it with centrality related measures.

Li14 calculated precision, how?

[52] Culhane AC, Schröder MS, Sultana R, et al: GeneSigDB: a manually curated database and resource for analysis of gene expression signatures. Nucleic acids research 2012, 40(D1):1060-1066.

Qin: Using a known-database to evaluate prediction. The precision of 60-80%. Did the authors address over-fitting problems? 

Tissue specific networks were constructed by removing unexpressed nodes.

References on removal method to generate tissue-specific networks

Waldman YY, Tuller T, Shlomi T, et al: Translation efficiency in humans: tissue specificity global optimization and differences between developmental stages. Nucleic Acids Research 2010, 38(9):2964-2974.

Bossi A, Lehner B: Tissue specificity and the human protein interaction network. Molecular Systems Biology 2009, 5(1):260.

Lopes TJ, Schaefer M, Shoemaker J, et al: Tissue-specific subnetworks and characteristics of publicly available human protein interaction databases. Bioinformatics 2011, 27(17):2414-2421.