Spectral Preprocessing for Clustering Time-Series Gene Expressions

<p/> <p>Based on gene expression profiles, genes can be partitioned into clusters, which might be associated with biological processes or functions, for example, cell cycle, circadian rhythm, and so forth. This paper proposes a novel clustering preprocessing strategy which combines clustering with spectral estimation techniques so that the time information present in time series gene expressions is fully exploited. By comparing the clustering results with a set of biologically annotated yeast cell-cycle genes, the proposed clustering strategy is corroborated to yield significantly different clusters from those created by the traditional expression-based schemes. The proposed technique is especially helpful in grouping genes participating in time-regulated processes.</p

Dynamic quantum clustering: a method for visual exploration of structures in data

A given set of data-points in some feature space may be associated with a Schrodinger equation whose potential is determined by the data. This is known to lead to good clustering solutions. Here we extend this approach into a full-fledged dynamical scheme using a time-dependent Schrodinger equation. Moreover, we approximate this Hamiltonian formalism by a truncated calculation within a set of Gaussian wave functions (coherent states) centered around the original points. This allows for analytic evaluation of the time evolution of all such states, opening up the possibility of exploration of relationships among data-points through observation of varying dynamical-distances among points and convergence of points into clusters. This formalism may be further supplemented by preprocessing, such as dimensional reduction through singular value decomposition or feature filtering.Comment: 15 pages, 9 figure

Laplacian Mixture Modeling for Network Analysis and Unsupervised Learning on Graphs

Laplacian mixture models identify overlapping regions of influence in unlabeled graph and network data in a scalable and computationally efficient way, yielding useful low-dimensional representations. By combining Laplacian eigenspace and finite mixture modeling methods, they provide probabilistic or fuzzy dimensionality reductions or domain decompositions for a variety of input data types, including mixture distributions, feature vectors, and graphs or networks. Provable optimal recovery using the algorithm is analytically shown for a nontrivial class of cluster graphs. Heuristic approximations for scalable high-performance implementations are described and empirically tested. Connections to PageRank and community detection in network analysis demonstrate the wide applicability of this approach. The origins of fuzzy spectral methods, beginning with generalized heat or diffusion equations in physics, are reviewed and summarized. Comparisons to other dimensionality reduction and clustering methods for challenging unsupervised machine learning problems are also discussed.Comment: 13 figures, 35 reference

Unmasking Clever Hans Predictors and Assessing What Machines Really Learn

Current learning machines have successfully solved hard application problems, reaching high accuracy and displaying seemingly "intelligent" behavior. Here we apply recent techniques for explaining decisions of state-of-the-art learning machines and analyze various tasks from computer vision and arcade games. This showcases a spectrum of problem-solving behaviors ranging from naive and short-sighted, to well-informed and strategic. We observe that standard performance evaluation metrics can be oblivious to distinguishing these diverse problem solving behaviors. Furthermore, we propose our semi-automated Spectral Relevance Analysis that provides a practically effective way of characterizing and validating the behavior of nonlinear learning machines. This helps to assess whether a learned model indeed delivers reliably for the problem that it was conceived for. Furthermore, our work intends to add a voice of caution to the ongoing excitement about machine intelligence and pledges to evaluate and judge some of these recent successes in a more nuanced manner.Comment: Accepted for publication in Nature Communication

Selecting Relevant Genes with a Spectral Approach

Array technologies have made it possible to record simultaneously the expression pattern of thousands of genes. A fundamental problem in the analysis of gene expression data is the identification of highly relevant genes that either discriminate between phenotypic labels or are important with respect to the cellular process studied in the experiment: for example cell cycle or heat shock in yeast experiments, chemical or genetic perturbations of mammalian cell lines, and genes involved in class discovery for human tumors. In this paper we focus on the task of unsupervised gene selection. The problem of selecting a small subset of genes is particularly challenging as the datasets involved are typically characterized by a very small sample size ?? the order of few tens of tissue samples ??d by a very large feature space as the number of genes tend to be in the high thousands. We propose a model independent approach which scores candidate gene selections using spectral properties of the candidate affinity matrix. The algorithm is very straightforward to implement yet contains a number of remarkable properties which guarantee consistent sparse selections. To illustrate the value of our approach we applied our algorithm on five different datasets. The first consists of time course data from four well studied Hematopoietic cell lines (HL-60, Jurkat, NB4, and U937). The other four datasets include three well studied treatment outcomes (large cell lymphoma, childhood medulloblastomas, breast tumors) and one unpublished dataset (lymph status). We compared our approach both with other unsupervised methods (SOM,PCA,GS) and with supervised methods (SNR,RMB,RFE). The results clearly show that our approach considerably outperforms all the other unsupervised approaches in our study, is competitive with supervised methods and in some case even outperforms supervised approaches