The complex regulatory network between microRNAs and gene expression remains an unclear domain of active research.We proposed to address in part this complex regulation with a novel approach for the genome-wide identification of biomodules derived from paired microRNA and mRNA profiles,which could reveal correlations associated with a complex network of dys-regulation in human cancer.Two published expression datasets for 68 samples with 11 distinct types of epithelial cancers and 21 samples of normal tissues were used,containing microRNA expression and gene expression profiles,respectively.As results,the microRNA expression used jointly with mRNA expression can provide better classifiers of epithelial cancers against normal epithelial tissue than either dataset alone(P=1×10-10,F-test).We identified a combination of 6 microRNA-mRNA biomodules that optimally classified epithelial cancers from normal epithelial tissue(total accuracy = 93.3%;95% confidence intervals:86%-97%),using penalized logistic regression(PLR) algorithm and three-fold cross-validation.Three of these biomodules are individually sufficient to cluster epithelial cancers from normal tissue using mutual information distance.The biomodules contain 10 distinct microRNAs and 98 distinct genes,including well known tumor markers such as miR-15a,miR-30e,IRAK1,TGFBR2,DUSP16,CDC25B and PDCD2.In addition,there is a significant enrichment(Fisher's exact test P=3×10-10) between putative microRNA-target gene pairs reported in 5 microRNA target databases and the inversely correlated microRNA-mRNA pairs in the biomodules.Further,microRNAs and genes in the biomodules were found in abstracts mentioning epithelial cancers(Fisher's Exact test,unadjusted P<0.05).Taken together,these results strongly suggest that the discovered microRNA-mRNA biomodules correspond to regulatory mechanisms common to human epithelial cancer samples.In conclusion,we developed and evaluated a novel comprehensive method to systematically identify,on a genome scale,microRNA-mRNA expression b
YANG XiNanLEE YoungheeFAN HongSUN XiaoLUSSIER Yves A
A sensitive approach for the qualitative detection of DNA-binding protein on the microarray was developed. DNA complexes in which a partial duplex region is formed from a biotin-primer and a circle single strand DNA （ssDNA） were spotted on a microarray. The endonuclease recognition site （ERS） and the DNA-binding sites （DBS） were arranged side by side within the duplex region. The working principle of the detection system is described as follows： when the DNA-binding protein capture the DBS, the endonuclease could not attach to the ERS, and the immobilized primer in the DNA complex could be extended along the circle ssDNA by rolling circle amplification （RCA）. When no protein protects the DBS, the ERS could be attacked by the endonuclease and subsequently no rolling circle amplification occurs. Thereby we can detect the sequence specific DNA-binding activity with high-sensitivity due to the signal amplification of RCA.
Min Li LiDong Rui ZhouHong ZhaoJin Ke WangZu Hong Lu
