Applications Of Bilinear Analysis And Integrative Hypothesis Testing In Gene Expression Analysis

microRNA called miRNA,is a class of about 22 nucleotides(nt)non-coding singlestranded RNA molecules from about 70 nt precursor miRNA(pre-miRNA)cutted by Dicer cleavage.miRNA is involved in a number of important life processes,including hematopoiesis,organogenesis,apoptosis and cell proliferation,and even cancer development.At present in the human genome about 500 miRNAs have been identified,of which at least 200 of their sequences have relation to cancer.RNA interference as a major scientific discovery in recent years,and this small molecule RNA which function as suppressors of protein synthesis become popular in the field of molecular biology studies.Since the researchers start to utilize RNA interference technology to treat cancer and other diseases,more and more clues showing a close relationship between miRNA and cancer have been revealed.Integrative Hypothesis Test(IHT)and Bilinear Analysis has been recently proposed for an integrated study of hypothesis test,classification analysis and feature selection.This paper not only applies IHT to identifying miRNAs biomarkers for the differentiation of lung cancer and Chronic Obstructive Pulmonary Disease(COPD),but also proposes a bootstrapping method to enhance the reliability of IHT ranking on samples with a small size and missing values.On the GEO data set GSE24709,the previously reported fourteen differentially expressed miRNAs have been re-confirmed via one by one enumeration of their IHT ranking,with two doubtful miRNAs identified.And Bilinear Analysis is studied by the liver cancer dataset GSE6857 with both tumor and peritumor gene expression data to differentiate metastasis and non-metastasis.Moreover,every pair of miRNAs is also exhaustively enumerated to examine the pairwise effect via the p-value,misclassification,and correlation,further identifying those that take core roles in coordinated effects.Furthermore,linked cliques are found featured with joint differentiation performances,which motivates us to identify such clique patterns as joint miRNAs biomarkers.