Integration of Ranked Lists via Cross Entropy Monte Carlo with Applications to mRNA and microRNA Studies

Abstract

One of the major challenges facing researchers studying complex biological systems is integration of data from -omics platforms. Omic-scale data include DNA variations, transcriptom profiles, and RAomics. Selection of an appropriate approach for a data-integration task is problem dependent, primarily dictated by the information contained in the data. In situations where modeling of multiple raw datasets jointly might be extremely challenging due to their vast differences, rankings from each dataset would provide a commonality based on which results could be integrated. Aggregation of microRNA targets predicted from different computational algorithms is such a problem. Integration of results from multiple mRNA studies based on different platforms is another example that will be discussed. Formulating the problem of integrating ranked lists as minimizing an objective criterion, we explore the usage of a cross entropy Monte Carlo method for solving such a combinatorial problem. Instead of placing a discrete uniform distribution on all the potential solutions, an iterative importance sampling technique is utilized "to slowly tighten the net" to place most distributional mass on the optimal solution and its neighbors. Extensive simulation studies were performed to assess the performance of the method. With satisfactory simulation results, the method was applied to the microRNA and mRNA problems to illustrate its utility.