Knowledge-based gene expression classification via matrix factorization

Motivation: Modern machine learning methods based on matrix decomposition techniques, like independent component analysis (ICA) or non-negative matrix factorization (NMF), provide new and efficient analysis tools which are currently explored to analyze gene expression profiles. These exploratory feature extraction techniques yield expression modes (ICA) or metagenes (NMF). These extracted features are considered indicative of underlying regulatory processes. They can as well be applied to the classification of gene expression datasets by grouping samples into different categories for diagnostic purposes or group genes into functional categories for further investigation of related metabolic pathways and regulatory networks. Results: In this study we focus on unsupervised matrix factorization techniques and apply ICA and sparse NMF to microarray datasets. The latter monitor the gene expression levels of human peripheral blood cells during differentiation from monocytes to macrophages. We show that these tools are able to identify relevant signatures in the deduced component matrices and extract informative sets of marker genes from these gene expression profiles. The methods rely on the joint discriminative power of a set of marker genes rather than on single marker genes. With these sets of marker genes, corroborated by leave-one-out or random forest cross-validation, the datasets could easily be classified into related diagnostic categories. The latter correspond to either monocytes versus macrophages or healthy vs Niemann Pick C disease patients.Siemens AG, MunichDFG (Graduate College 638)DAAD (PPP Luso - Alem˜a and PPP Hispano - Alemanas

The independent component analysis with the linear regression – predicting the energy costs of the public sector buildings in Croatia

In the European Union, the public sector buildings are considered significant energy consumers and are, thus, the subject of several directives that aim to ensure the renovation of existing and the construction of new buildings as nearly zero-energy buildings. Therefore, as part of the decision making, it is necessary to properly plan the renovation or construction. This research provides models for predicting the energy costs of the public sector buildings, which are dependent upon its characteristics (i. e., constructional, occupational, energy, etc.). For this purpose, a real data set of Croatian public buildings was used, which included 150 variables and 1724 observations. Since the data set consisted of a large number of variables, the motivation for the dimensionality reduction was addressed first. Then, the independent component analysis, the principal component analysis, and the factor analysis were performed as the dimensionality reduction methods for variable extraction. The results of these analyses were used as inputs for modelling the energy costs of the public sector buildings. The obtained models were compared to the model built on original variables. The obtained models show the application potential in decision making for building renovation and construction in the public sector of Croatia, whereas the best performance of prediction in terms of RMSE and SMAPE was achieved by the model that integrated the independent component analysis with the linear regression

Postgenomics: Proteomics and Bioinformatics in Cancer Research

Now that the human genome is completed, the characterization of the proteins encoded by the sequence remains a challenging task. The study of the complete protein complement of the genome, the “proteome,” referred to as proteomics, will be essential if new therapeutic drugs and new disease biomarkers for early diagnosis are to be developed. Research efforts are already underway to develop the technology necessary to compare the specific protein profiles of diseased versus nondiseased states. These technologies provide a wealth of information and rapidly generate large quantities of data. Processing the large amounts of data will lead to useful predictive mathematical descriptions of biological systems which will permit rapid identification of novel therapeutic targets and identification of metabolic disorders. Here, we present an overview of the current status and future research approaches in defining the cancer cell's proteome in combination with different bioinformatics and computational biology tools toward a better understanding of health and disease

Classification of microarray gene expression cancer data by using artificial intelligence methods

Günümüzde bilgisayar teknolojilerinin gelişmesi ile birçok alanda yapılan çalışmaları etkilemiştir. Moleküler biyoloji ve bilgisayar teknolojilerinde meydana gelen gelişmeler biyoinformatik adlı bilimi ortaya çıkarmıştır. Biyoinformatik alanında meydana gelen hızlı gelişmeler, bu alanda çözülmeyi bekleyen birçok probleme çözüm olma yolunda büyük katkılar sağlamıştır. DNA mikroarray gen ekspresyonlarının sınıflandırılması da bu problemlerden birisidir. DNA mikroarray çalışmaları, biyoinformatik alanında kullanılan bir teknolojidir. DNA mikroarray veri analizi, kanser gibi genlerle alakalı hastalıkların teşhisinde çok etkin bir rol oynamaktadır. Hastalık türüne bağlı gen ifadeleri belirlenerek, herhangi bir bireyin hastalıklı gene sahip olup olmadığı büyük bir başarı oranı ile tespit edilebilir. Bireyin sağlıklı olup olmadığının tespiti için, mikroarray gen ekspresyonları üzerinde yüksek performanslı sınıflandırma tekniklerinin kullanılması büyük öneme sahiptir. DNA mikroarray’lerini sınıflandırmak için birçok yöntem bulunmaktadır. Destek Vektör Makinaları, Naive Bayes, k-En yakın Komşu, Karar Ağaçları gibi birçok istatistiksel yöntemler yaygın olarak kullanlmaktadır. Fakat bu yöntemler tek başına kullanıldığında, mikroarray verilerini sınıflandırmada her zaman yüksek başarı oranları vermemektedir. Bu yüzden mikroarray verilerini sınıflandırmada yüksek başarı oranları elde etmek için yapay zekâ tabanlı yöntemlerin de kullanılması yapılan çalışmalarda görülmektedir. Bu çalışmada, bu istatistiksel yöntemlere ek olarak yapay zekâ tabanlı ANFIS gibi bir yöntemi kullanarak daha yüksek başarı oranları elde etmek amaçlanmıştır. İstatistiksel sınıflandırma yöntemleri olarak K-En Yakın Komşuluk, Naive Bayes ve Destek Vektör Makineleri kullanılmıştır. Burada Göğüs ve Merkezi Sinir Sistemi kanseri olmak üzere iki farklı kanser veri seti üzerinde çalışmalar yapılmıştır. Sonuçlardan elde edilen bilgilere göre, genel olarak yapay zekâ tabanlı ANFIS tekniğinin, istatistiksel yöntemlere göre daha başarılı olduğu tespit edilmiştir

Restricting Supervised Learning: Feature Selection and Feature Space Partition

Many supervised learning problems are considered difficult to solve either because of the redundant features or because of the structural complexity of the generative function. Redundant features increase the learning noise and therefore decrease the prediction performance. Additionally, a number of problems in various applications such as bioinformatics or image processing, whose data are sampled in a high dimensional space, suffer the curse of dimensionality, and there are not enough observations to obtain good estimates. Therefore, it is necessary to reduce such features under consideration. Another issue of supervised learning is caused by the complexity of an unknown generative model. To obtain a low variance predictor, linear or other simple functions are normally suggested, but they usually result in high bias. Hence, a possible solution is to partition the feature space into multiple non-overlapping regions such that each region is simple enough to be classified easily. In this dissertation, we proposed several novel techniques for restricting supervised learning problems with respect to either feature selection or feature space partition. Among different feature selection methods, 1-norm regularization is advocated by many researchers because it incorporates feature selection as part of the learning process. We give special focus here on ranking problems because very little work has been done for ranking using L1 penalty. We present here a 1-norm support vector machine method to simultaneously find a linear ranking function and to perform feature subset selection in ranking problems. Additionally, because ranking is formulated as a classification task when pair-wise data are considered, it increases the computational complexity from linear to quadratic in terms of sample size. We also propose a convex hull reduction method to reduce this impact. The method was tested on one artificial data set and two benchmark real data sets, concrete compressive strength set and Abalone data set. Theoretically, by tuning the trade-off parameter between the 1-norm penalty and the empirical error, any desired size of feature subset could be achieved, but computing the whole solution path in terms of the trade-off parameter is extremely difficult. Therefore, using 1-norm regularization alone may not end up with a feature subset of small size. We propose a recursive feature selection method based on 1-norm regularization which can handle the multi-class setting effectively and efficiently. The selection is performed iteratively. In each iteration, a linear multi-class classifier is trained using 1-norm regularization, which leads to sparse weight vectors, i.e., many feature weights are exactly zero. Those zero-weight features are eliminated in the next iteration. The selection process has a fast rate of convergence. We tested our method on an earthworm microarray data set and the empirical results demonstrate that the selected features (genes) have very competitive discriminative power. Feature space partition separates a complex learning problem into multiple non-overlapping simple sub-problems. It is normally implemented in a hierarchical fashion. Different from decision tree, a leaf node of this hierarchical structure does not represent a single decision, but represents a region (sub-problem) that is solvable with respect to linear functions or other simple functions. In our work, we incorporate domain knowledge in the feature space partition process. We consider domain information encoded by discrete or categorical attributes. A discrete or categorical attribute provides a natural partition of the problem domain, and hence divides the original problem into several non-overlapping sub-problems. In this sense, the domain information is useful if the partition simplifies the learning task. However it is not trivial to select the discrete or categorical attribute that maximally simplify the learning task. A naive approach exhaustively searches all the possible restructured problems. It is computationally prohibitive when the number of discrete or categorical attributes is large. We describe a metric to rank attributes according to their potential to reduce the uncertainty of a classification task. It is quantified as a conditional entropy achieved using a set of optimal classifiers, each of which is built for a sub-problem defined by the attribute under consideration. To avoid high computational cost, we approximate the solution by the expected minimum conditional entropy with respect to random projections. This approach was tested on three artificial data sets, three cheminformatics data sets, and two leukemia gene expression data sets. Empirical results demonstrate that our method is capable of selecting a proper discrete or categorical attribute to simplify the problem, i.e., the performance of the classifier built for the restructured problem always beats that of the original problem. Restricting supervised learning is always about building simple learning functions using a limited number of features. Top Selected Pair (TSP) method builds simple classifiers based on very few (for example, two) features with simple arithmetic calculation. However, traditional TSP method only deals with static data. In this dissertation, we propose classification methods for time series data that only depend on a few pairs of features. Based on the different comparison strategies, we developed the following approaches: TSP based on average, TSP based on trend, and TSP based on trend and absolute difference amount. In addition, inspired by the idea of using two features, we propose a time series classification method based on few feature pairs using dynamic time warping and nearest neighbor

Statistical analysis of high-dimensional biomedical data: a gentle introduction to analytical goals, common approaches and challenges

International audienceBackground: In high-dimensional data (HDD) settings, the number of variables associated with each observation is very large. Prominent examples of HDD in biomedical research include omics data with a large number of variables such as many measurements across the genome, proteome, or metabolome, as well as electronic health records data that have large numbers of variables recorded for each patient. The statistical analysis of such data requires knowledge and experience, sometimes of complex methods adapted to the respective research questions. Methods: Advances in statistical methodology and machine learning methods offer new opportunities for innovative analyses of HDD, but at the same time require a deeper understanding of some fundamental statistical concepts. Topic group TG9 “High-dimensional data” of the STRATOS (STRengthening Analytical Thinking for Observational Studies) initiative provides guidance for the analysis of observational studies, addressing particular statistical challenges and opportunities for the analysis of studies involving HDD. In this overview, we discuss key aspects of HDD analysis to provide a gentle introduction for non-statisticians and for classically trained statisticians with little experience specific to HDD. Results: The paper is organized with respect to subtopics that are most relevant for the analysis of HDD, in particular initial data analysis, exploratory data analysis, multiple testing, and prediction. For each subtopic, main analytical goals in HDD settings are outlined. For each of these goals, basic explanations for some commonly used analysis methods are provided. Situations are identified where traditional statistical methods cannot, or should not, be used in the HDD setting, or where adequate analytic tools are still lacking. Many key references are provided. Conclusions: This review aims to provide a solid statistical foundation for researchers, including statisticians and non-statisticians, who are new to research with HDD or simply want to better evaluate and understand the results of HDD analyses

Gene Expression Analysis Methods on Microarray Data a A Review

In recent years a new type of experiments are changing the way that biologists and other specialists analyze many problems. These are called high throughput experiments and the main difference with those that were performed some years ago is mainly in the quantity of the data obtained from them. Thanks to the technology known generically as microarrays, it is possible to study nowadays in a single experiment the behavior of all the genes of an organism under different conditions. The data generated by these experiments may consist from thousands to millions of variables and they pose many challenges to the scientists who have to analyze them. Many of these are of statistical nature and will be the center of this review. There are many types of microarrays which have been developed to answer different biological questions and some of them will be explained later. For the sake of simplicity we start with the most well known ones: expression microarrays

Evaluation of Multiple Models to Distinguish Closely Related Forms of Disease Using DNA Microarray Data: an Application to Multiple Myeloma

Motivation: Standard laboratory classification of the plasma cell dyscrasia monoclonal gammopathy of undetermined significance (MGUS) and the overt plasma cell neoplasm multiple myeloma (MM) is quite accurate, yet, for the most part, biologically uninformative. Most, if not all, cancers are caused by inherited or acquired genetic mutations that manifest themselves in altered gene expression patterns in the clonally related cancer cells. Microarray technology allows for qualitative and quantitative measurements of the expression levels of thousands of genes simultaneously, and it has now been used both to classify cancers that are morphologically indistinguishable and to predict response to therapy. It is anticipated that this information can also be used to develop molecular diagnostic models and to provide insight into mechanisms of disease progression, e.g., transition from healthy to benign hyperplasia or conversion of a benign hyperplasia to overt malignancy. However, standard data analysis techniques are not trivial to employ on these large data sets. Methodology designed to handle large data sets (or modified to do so) is needed to access the vital information contained in the genetic samples, which in turn can be used to develop more robust and accurate methods of clinical diagnostics and prognostics.Results: Here we report on the application of a panel of statistical and data mining methodologies to classify groups of samples based on expression of 12,000 genes derived from a high density oligonucleotide microarray analysis of highly purified plasma cells from newly diagnosed MM, MGUS, and normal healthy donors. The three groups of samples are each tested against each other. The methods are found to be similar in their ability to predict group membership; all do quite well at predicting MM vs. normal and MGUS vs. normal. However, no method appears to be able to distinguish explicitly the genetic mechanisms between MM and MGUS. We believe this might be due to the lack of genetic differences between these two conditions, and may not be due to the failure of the models. We report the prediction errors for each of the models and each of the methods. Additionally, we report ROC curves for the results on group prediction.Availability: Logistic regression: standard software, available, for example in SAS. Decision trees and boosted trees: C5.0 from www.rulequest.com. SVM: SVM-light is publicly available from svmlight.joachims.org. Naïve Bayes and ensemble of voters are publicly available from www.biostat.wisc.edu/~mwaddell/eov.html. Nearest Shrunken Centroids is publicly available from http://www-stat.stanford.edu/~tibs/PAM

Multi Layer Analysis

This thesis presents a new methodology to analyze one-dimensional signals trough a new approach called Multi Layer Analysis, for short MLA. It also provides some new insights on the relationship between one-dimensional signals processed by MLA and tree kernels, test of randomness and signal processing techniques. The MLA approach has a wide range of application to the fields of pattern discovery and matching, computational biology and many other areas of computer science and signal processing. This thesis includes also some applications of this approach to real problems in biology and seismology