With different genomes available, unsupervised learning algorithms are essential in learning genome-wide biological insights. Especially, the functional characterization of different genomes is essential for us to understand lives. In this book chapter, we review the state-of-the-art unsupervised learning algorithms for genome informatics from DNA to MicroRNA. DNA (DeoxyriboNucleic Acid) is the basic component of genomes. A significant fraction of DNA regions (transcription factor binding sites) are bound by proteins (transcription factors) to regulate gene expression at different development stages in different tissues. To fully understand genetics, it is necessary of us to apply unsupervised learning algorithms to learn and infer those DNA regions. Here we review several unsupervised learning methods for deciphering the genome-wide patterns of those DNA regions. MicroRNA (miRNA), a class of small endogenous non-coding RNA (RiboNucleic acid) species, regulate gene expression post-transcriptionally by forming imperfect base-pair with the target sites primarily at the 3$'$ untranslated regions of the messenger RNAs. Since the 1993 discovery of the first miRNA \emph{let-7} in worms, a vast amount of studies have been dedicated to functionally characterizing the functional impacts of miRNA in a network context to understand complex diseases such as cancer. Here we review several representative unsupervised learning frameworks on inferring miRNA regulatory network by exploiting the static sequence-based information pertinent to the prior knowledge of miRNA targeting and the dynamic information of miRNA activities implicated by the recently available large data compendia, which interrogate genome-wide expression profiles of miRNAs and/or mRNAs across various cell conditions.

Previously, we proposed a physically-inspired method to construct data points into an effective in-tree (IT) structure, in which the underlying cluster structure in the dataset is well revealed. Although there are some edges in the IT structure requiring to be removed, such undesired edges are generally distinguishable from other edges and thus are easy to be determined. For instance, when the IT structures for the 2-dimensional (2D) datasets are graphically presented, those undesired edges can be easily spotted and interactively determined. However, in practice, there are many datasets that do not lie in the 2D Euclidean space, thus their IT structures cannot be graphically presented. But if we can effectively map those IT structures into a visualized space in which the salient features of those undesired edges are preserved, then the undesired edges in the IT structures can still be visually determined in a visualization environment. Previously, this purpose was reached by our method called IT-map. The outstanding advantage of IT-map is that clusters can still be found even with the so-called crowding problem in the embedding. In this paper, we propose another method, called IT-Dendrogram, to achieve the same goal through an effective combination of the IT structure and the single link hierarchical clustering (SLHC) method. Like IT-map, IT-Dendrogram can also effectively represent the IT structures in a visualization environment, whereas using another form, called the Dendrogram. IT-Dendrogram can serve as another visualization method to determine the undesired edges in the IT structures and thus benefit the IT-based clustering analysis. This was demonstrated on several datasets with different shapes, dimensions, and attributes. Unlike IT-map, IT-Dendrogram can always avoid the crowding problem, which could help users make more reliable cluster analysis in certain problems.

Symbolic Data Analysis is based on special descriptions of data - symbolic objects (SO). Such descriptions preserve more detailed information about units and their clusters than the usual representations with mean values. A special kind of symbolic object is a representation with frequency or probability distributions (modal values). This representation enables us to consider in the clustering process the variables of all measurement types at the same time. In the paper a clustering criterion function for SOs is proposed such that the representative of each cluster is again composed of distributions of variables' values over the cluster. The corresponding leaders clustering method is based on this result. It is also shown that for the corresponding agglomerative hierarchical method a generalized Ward's formula holds. Both methods are compatible - they are solving the same clustering optimization problem. The leaders method efficiently solves clustering problems with large number of units; while the agglomerative method can be applied alone on the smaller data set, or it could be applied on leaders, obtained with compatible nonhierarchical clustering method. Such a combination of two compatible methods enables us to decide upon the right number of clusters on the basis of the corresponding dendrogram. The proposed methods were applied on different data sets. In the paper, some results of clustering of ESS data are presented.

Mixture models are powerful statistical models used in many applications ranging from density estimation to clustering and classification. When dealing with mixture models, there are many issues that the experimenter should be aware of and needs to solve. The MixEst toolbox is a powerful and user-friendly package for MATLAB that implements several state-of-the-art approaches to address these problems. Additionally, MixEst gives the possibility of using manifold optimization for fitting the density model, a feature specific to this toolbox. MixEst simplifies using and integration of mixture models in statistical models and applications. For developing mixture models of new densities, the user just needs to provide a few functions for that statistical distribution and the toolbox takes care of all the issues regarding mixture models. MixEst is available at visionlab.ut.ac.ir/mixest and is fully documented and is licensed under GPL.

Multiplex networks, a special type of multilayer networks, are increasingly applied in many domains ranging from social media analytics to biology. A common task in these applications concerns the detection of community structures. Many existing algorithms for community detection in multiplexes attempt to detect communities which are shared by all layers. In this article we propose a community detection algorithm, LART (Locally Adaptive Random Transitions), for the detection of communities that are shared by either some or all the layers in the multiplex. The algorithm is based on a random walk on the multiplex, and the transition probabilities defining the random walk are allowed to depend on the local topological similarity between layers at any given node so as to facilitate the exploration of communities across layers. Based on this random walk, a node dissimilarity measure is derived and nodes are clustered based on this distance in a hierarchical fashion. We present experimental results using networks simulated under various scenarios to showcase the performance of LART in comparison to related community detection algorithms.

We develop an iterative subsampling approach to improve the computational efficiency of our previous work on solution path clustering (SPC). The SPC method achieves clustering by concave regularization on the pairwise distances between cluster centers. This clustering method has the important capability to recognize noise and to provide a short path of clustering solutions; however, it is not sufficiently fast for big datasets. Thus, we propose a method that iterates between clustering a small subsample of the full data and sequentially assigning the other data points to attain orders of magnitude of computational savings. The new method preserves the ability to isolate noise, includes a solution selection mechanism that ultimately provides one clustering solution with an estimated number of clusters, and is shown to be able to extract small tight clusters from noisy data. The method's relatively minor losses in accuracy are demonstrated through simulation studies, and its ability to handle large datasets is illustrated through applications to gene expression datasets. An R package, SPClustering, for the SPC method with iterative subsampling is available at http://www.stat.ucla.edu/~zhou/Software.html.

We address an ensemble clustering problem, where reliable clusters are locally embedded in given multiple partitions. We propose a new nonnegative matrix factorization (NMF)-based method, in which locally reliable clusters are explicitly considered by using instance-wise weights over clusters. Our method factorizes the input cluster assignment matrix into two matrices H and W, which are optimized by iteratively 1) updating H and W while keeping the weight matrix constant and 2) updating the weight matrix while keeping H and W constant, alternatively. The weights in the second step were updated by solving a convex problem, which makes our algorithm significantly faster than existing NMF-based ensemble clustering methods. We empirically proved that our method outperformed a lot of cutting-edge ensemble clustering methods by using a variety of datasets.

We address an ensemble clustering problem, where reliable clusters are locally embedded in given multiple partitions. We propose a new nonnegative matrix factorization (NMF)-based method, in which locally reliable clusters are explicitly considered by using instance-wise weights over clusters. Our method factorizes the input cluster assignment matrix into two matrices H and W, which are optimized by iteratively 1) updating H and W while keeping the weight matrix constant and 2) updating the weight matrix while keeping H and W constant, alternatively. The weights in the second step were updated by solving a convex problem, which makes our algorithm significantly faster than existing NMF-based ensemble clustering methods. We empirically proved that our method outperformed a lot of cutting-edge ensemble clustering methods by using a variety of datasets.

We address an ensemble clustering problem, where reliable clusters are locally embedded in given multiple partitions. We propose a new nonnegative matrix factorization (NMF)-based method, in which locally reliable clusters are explicitly considered by using instance-wise weights over clusters. Our method factorizes the input cluster assignment matrix into two matrices H and W, which are optimized by iteratively 1) updating H and W while keeping the weight matrix constant and 2) updating the weight matrix while keeping H and W constant, alternatively. The weights in the second step were updated by solving a convex problem, which makes our algorithm significantly faster than existing NMF-based ensemble clustering methods. We empirically proved that our method outperformed a lot of cutting-edge ensemble clustering methods by using a variety of datasets.

We address an ensemble clustering problem, where reliable clusters are locally embedded in given multiple partitions. We propose a new nonnegative matrix factorization (NMF)-based method, in which locally reliable clusters are explicitly considered by using instance-wise weights over clusters. Our method factorizes the input cluster assignment matrix into two matrices H and W, which are optimized by iteratively 1) updating H and W while keeping the weight matrix constant and 2) updating the weight matrix while keeping H and W constant, alternatively. The weights in the second step were updated by solving a convex problem, which makes our algorithm significantly faster than existing NMF-based ensemble clustering methods. We empirically proved that our method outperformed a lot of cutting-edge ensemble clustering methods by using a variety of datasets.