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Background: Quantitative simultaneous monitoring of the expression levels of thousands of genes under various experimental conditions is now possible using microarray experiments. However, there are still gaps toward whole-genome functional annotation of genes using the gene expression data., Results: In this paper, we propose a novel technique called Fuzzy Nearest Clusters for genome-wide functional annotation of unclassified genes. The technique consists of two steps: an initial hierarchical clustering step to detect homogeneous co-expressed gene subgroups or clusters in each possibly heterogeneous functional class; followed by a classification step to predict the functional roles of the unclassified genes based on their corresponding similarities to the detected functional clusters., Conclusion: Our experimental results with yeast gene expression data showed that the proposed method can accurately predict the genes' functions, even those with multiple functional roles, and the prediction performance is most independent of the underlying heterogeneity of the complex functional classes, as compared to the other conventional gene function prediction approaches.

Background: Proteins dynamically interact with each other to perform their biological functions. The dynamic operations of protein interaction networks (PPI) are also reflected in the dynamic formations of protein complexes. Existing protein complex detection algorithms usually overlook the inherent temporal nature of protein interactions within PPI networks. Systematically analyzing the temporal protein complexes can not only improve the accuracy of protein complex detection, but also strengthen our biological knowledge on the dynamic protein assembly processes for cellular organization. Results: In this study, we propose a novel computational method to predict temporal protein complexes. Particularly, we first construct a series of dynamic PPI networks by joint analysis of time-course gene expression data and protein interaction data. Then a Time Smooth Overlapping Complex Detection model (TS-OCD) has been proposed to detect temporal protein complexes from these dynamic PPI networks. TS-OCD can naturally capture the smoothness of networks between consecutive time points and detect overlapping protein complexes at each time point. Finally, a nonnegative matrix factorization based algorithm is introduced to merge those very similar temporal complexes across different time points. Conclusions: Extensive experimental results demonstrate the proposed method is very effective in detecting temporal protein complexes than the state-of-the-art complex detection techniques. [ABSTRACT FROM AUTHOR]

Background: Although high-throughput microarray based molecular diagnostic technologies show a great promise in cancer diagnosis, it is still far from a clinical application due to its low and instable sensitivities and specificities in cancer molecular pattern recognition. In fact, high-dimensional and heterogeneous tumor profiles challenge current machine learning methodologies for its small number of samples and large or even huge number of variables (genes). This naturally calls for the use of an effective feature selection in microarray data classification. Methods: We propose a novel feature selection method: multi-resolution independent component analysis (MICA) for large-scale gene expression data. This method overcomes the weak points of the widely used transform-based feature selection methods such as principal component analysis (PCA), independent component analysis (ICA), and nonnegative matrix factorization (NMF) by avoiding their global feature-selection mechanism. In addition to demonstrating the effectiveness of the multi-resolution independent component analysis in meaningful biomarker discovery, we present a multi-resolution independent component analysis based support vector machines (MICASVM) and linear discriminant analysis (MICA-LDA) to attain high-performance classifications in low-dimensional spaces. Results: We have demonstrated the superiority and stability of our algorithms by performing comprehensive experimental comparisons with nine state-of-the-art algorithms on six high-dimensional heterogeneous profiles under cross validations. Our classification algorithms, especially, MICA-SVM, not only accomplish clinical or near-clinical level sensitivities and specificities, but also show strong performance stability over its peers in classification. Software that implements the major algorithm and data sets on which this paper focuses are freely available at https://sites.google.com/site/heyaumapbc2011/. Conclusions: This work suggests a new direction to accelerate microarray technologies into a clinical routine through building a high-performance classifier to attain clinical-level sensitivities and specificities by treating an input profile as a 'profile-biomarker'. The multi-resolution data analysis based redundant global feature suppressing and effective local feature extraction also have a positive impact on large scale 'omics' data mining. [ABSTRACT FROM AUTHOR]