Genetic association study (GAS) is a promising tool for detecting and analyzing the cause of complex diseases. The extreme learning machine (ELM) has been successfully applied in a variety of research fields. Yet, as a black box method, it could not measure up to the task of GAS by itself, because it cannot tell us what causes the diseases, which is very crucial to the biologists. In this paper, we propose an ELM-based statistically significant pattern classification framework, which combines ELM with feature vector-based methods to solve the GAS problem efficiently and effectively. In particular: 1) a statistically significant pattern considering in terms of both family wise error rate (FWER) and false discovery rate (FDR) is proposed to control false positives in multiple hypothesis tests, which is necessary in GAS, but ignored by most of the existing methods; 2) an upper bound of the significance of a pattern is deduced to speed up FWER-constrained statistically significant pattern mining in a row enumeration way. Further, a space-effective grid index is devised to dramatically improves the efficiency of FDR-constrained pattern discovery; and 3) an ELM classifier is constructed based on the significant patterns. Comprehensive empirical studies on four real genotype datasets demonstrate much higher efficiency and effectiveness of our proposed framework with respect to the compared methods.

Advanced microarray technologies have enabled to simultaneously monitor the expression levels of all genes. An important problem in microarray data analysis is to discover phenotype structures. The goal is to 1) find groups of samples corresponding to different phenotypes (such as disease or normal), and 2) for each group of samples, find the representative expression pattern or signature that distinguishes this group from others. Some methods have been proposed for this issue, however, a common drawback is that the identified signatures often include a large number of genes but with low discriminative power. In this paper, we propose a $(g^\ast)$-sequence model to address this limitation, where the ordered expression values among genes are profitably utilized. Compared with the existing methods, the proposed sequence model is more robust to noise and allows to discover the signatures with more discriminative power using fewer genes. This is important for the subsequent analysis by the biologists. We prove that the problem of phenotype structure discovery is NP-complete. An efficient algorithm, FINDER, is developed, which includes three steps: 1) trivial $(g^\ast)$-sequences identifying, 2) phenotype structure discovery, and 3) refinement. Effective pruning strategies are developed to further improve the efficiency. We evaluate the performance of FINDER and the existing methods using both synthetic and real gene expression data sets. Extensive experimental results show that FINDER dramatically improves the accuracy of the phenotype structures discovered (in terms of both statistical and biological significance) and detects signatures with high discriminative power. Moreover, it is orders of magnitude faster than other alternatives.

Diagnostic genes refer to the genes closely related to a specific disease phenotype, the powers of which to distinguish between different classes are often high. Most methods to discovering the powerful diagnostic genes are either singleton discriminability-based or combination discriminability-based. However, both ignore the abundant interactions among genes, which widely exist in the real world. In this paper, we tackle the problem from a new point of view and make the following contributions: (1) we propose an EWave model, which profitably exploits the ordered expressions among genes based on the defined equivalent dimension group sequences taking into account the "noise" universal in the real data, (2) we devise a novel sequence rule, namely interesting non-redundant contrast sequence rule, which is able to capture the difference between different phenotypes in a high accuracy using as few as possible genes, (3) we present an efficient algorithm called NRMINER to find such rules. Unlike the conventional column enumeration and the more recent row enumeration, it performs a novel template-driven enumeration by making use of the special characteristic of micro array data modeled by EWave. Extensive experiments conducted on various synthetic and real datasets show that: (1) NRMINER is significantly faster than the competing algorithm by up to about one order of magnitude, (2) it provides a higher accuracy using fewer genes. Many diagnostic genes discovered by NRMINER are proved biologically related to some disease.