Collaborative Sliced Inverse Regression

International audienceSliced Inverse Regression (SIR) is an effective method for dimensionality reduction in high-dimensional regression problems. However, the method has requirements on the distribution of the predictors that are hard to check since they depend on unobserved variables. It has been shown that, if the distribution of the predictors is elliptical, then these requirements are satisfied.In case of mixture models, the ellipticity is violated and in addition there is no assurance of a single underlying regression model among the different components. Our approach clusterizes the predictors space to force the condition to hold on each cluster and includes a merging technique to look for different underlying models in the data. A study on simulated data as well as two real applications are provided. It appears that SIR, unsurprisingly, is not capable of dealing with a mixture of Gaussians involving different underlying models whereas our approach is able to correctly investigate the mixture

Censored Data Regression in High-Dimension and Low-Sample Size Settings For Genomic Applications

New high-throughput technologies are generating various types of high-dimensional genomic and proteomic data and meta-data (e.g., networks and pathways) in order to obtain a systems-level understanding of various complex diseases such as human cancers and cardiovascular diseases. As the amount and complexity of the data increase and as the questions being addressed become more sophisticated, we face the great challenge of how to model such data in order to draw valid statistical and biological conclusions. One important problem in genomic research is to relate these high-throughput genomic data to various clinical outcomes, including possibly censored survival outcomes such as age at disease onset or time to cancer recurrence. We review some recently developed methods for censored data regression in the high-dimension and low-sample size setting, with emphasis on applications to genomic data. These methods include dimension reduction-based methods, regularized estimation methods such as Lasso and threshold gradient descent method, gradient descent boosting methods and nonparametric pathways-based regression models. These methods are demonstrated and compared by analysis of a data set of microarray gene expression profiles of 240 patients with diffuse large B-cell lymphoma together with follow-up survival information. Areas of further research are also presented

A method for analyzing censored survival phenotype with gene expression data

<p>Abstract</p> <p>Background</p> <p>Survival time is an important clinical trait for many disease studies. Previous works have shown certain relationship between patients' gene expression profiles and survival time. However, due to the censoring effects of survival time and the high dimensionality of gene expression data, effective and unbiased selection of a gene expression signature to predict survival probabilities requires further study.</p> <p>Method</p> <p>We propose a method for an integrated study of survival time and gene expression. This method can be summarized as a two-step procedure: in the first step, a moderate number of genes are pre-selected using correlation or liquid association (LA). Imputation and transformation methods are employed for the correlation/LA calculation. In the second step, the dimension of the predictors is further reduced using the modified sliced inverse regression for censored data (censorSIR).</p> <p>Results</p> <p>The new method is tested via both simulated and real data. For the real data application, we employed a set of 295 breast cancer patients and found a linear combination of 22 gene expression profiles that are significantly correlated with patients' survival rate.</p> <p>Conclusion</p> <p>By an appropriate combination of feature selection and dimension reduction, we find a method of identifying gene expression signatures which is effective for survival prediction.</p

A new sliced inverse regression method for multivariate response

International audienceA semiparametric regression model of a q-dimensional multivariate response y on a p-dimensional covariate x is considered. A new approach is proposed based on sliced inverse regression (SIR) for estimating the effective dimension reduction (EDR) space without requiring a prespecified parametric model. The convergence at rate square root of n of the estimated EDR space is shown. The choice of the dimension of the EDR space is discussed. Moreover, a way to cluster components of y related to the same EDR space is provided. Thus, the proposed multivariate SIR method can be used properly on each cluster instead of blindly applying it on all components of y. The numerical performances of multivariate SIR are illustrated on a simulation study. Applications to a remote sensing dataset and to the Minneapolis elementary schools data are also provided. Although the proposed methodology relies on SIR, it opens the door for new regression approaches with a multivariate response

Joint covariate selection and joint subspace selection for multiple classification problems

We address the problem of recovering a common set of covariates that are relevant simultaneously to several classification problems. By penalizing the sum of ℓ2-norms of the blocks of coefficients associated with each covariate across different classification problems, similar sparsity patterns in all models are encouraged. To take computational advantage of the sparsity of solutions at high regularization levels, we propose a blockwise path-following scheme that approximately traces the regularization path. As the regularization coefficient decreases, the algorithm maintains and updates concurrently a growing set of covariates that are simultaneously active for all problems. We also show how to use random projections to extend this approach to the problem of joint subspace selection, where multiple predictors are found in a common low-dimensional subspace. We present theoretical results showing that this random projection approach converges to the solution yielded by trace-norm regularization. Finally, we present a variety of experimental results exploring joint covariate selection and joint subspace selection, comparing the path-following approach to competing algorithms in terms of prediction accuracy and running time

BIOINFORMATICS ANALYSIS OF OMICS DATA TOWARDS CANCER DIAGNOSIS AND PROGNOSIS

I would first like to thank my mentor, Dr. Arul M. Chinnaiyan, for his expert guidance, support, encouragement, and inspiration. I would also like to thank Dr. Debashis Ghosh for his continuous statistical support and great advice, Dr. David G. Beer, Dr. Jill A. Macoska, and Dr. Kerby A. Shedden for serving on my Doctoral committee and giving me valuable suggestions on this thesis work. I would like to thank Jindan Yu, Xiaoju Wang, Guoan Chen, Saravana Dhanasekaran, Daniel Rhodes, Scott A. Tomlins, and Sooryanarayana Varambally, who have contributed to most of the work described here. I would like to express my gratitude to all the members in the Chinnaiyan lab for their support. Without them, none of the work described here could have been completed. I would also like to thank William P. Worzel and Arpit A. Almal for their support on genetic programming project. I would like to express my deepest gratitude to my wife and my love, Yipin, without whom I would be nowhere. Thanks for putting up with my late nights and giving me unconditional love and encouragement through my Doctoral study and the writing of this work. I would also like to thank my parents, my sister, and my grandparents for giving constant support and love. And last but not least, I would like to thank my friends and all whose support helped me completing this thesis in time. ii TABLE OF CONTENT

Integrated smoothed location model and data reduction approaches for multi variables classification

Smoothed Location Model is a classification rule that deals with mixture of continuous variables and binary variables simultaneously. This rule discriminates groups in a parametric form using conditional distribution of the continuous variables given each pattern of the binary variables. To conduct a practical classification analysis, the objects must first be sorted into the cells of a multinomial table generated from the binary variables. Then, the parameters in each cell will be estimated using the sorted objects. However, in many situations, the estimated parameters are poor if the number of binary is large relative to the size of sample. Large binary variables will create too many multinomial cells which are empty, leading to high sparsity problem and finally give exceedingly poor performance for the constructed rule. In the worst case scenario, the rule cannot be constructed. To overcome such shortcomings, this study proposes new strategies to extract adequate variables that contribute to optimum performance of the rule. Combinations of two extraction techniques are introduced, namely 2PCA and PCA+MCA with new cutpoints of eigenvalue and total variance explained, to determine adequate extracted variables which lead to minimum misclassification rate. The outcomes from these extraction techniques are used to construct the smoothed location models, which then produce two new approaches of classification called 2PCALM and 2DLM. Numerical evidence from simulation studies demonstrates that the computed misclassification rate indicates no significant difference between the extraction techniques in normal and non-normal data. Nevertheless, both proposed approaches are slightly affected for non-normal data and severely affected for highly overlapping groups. Investigations on some real data sets show that the two approaches are competitive with, and better than other existing classification methods. The overall findings reveal that both proposed approaches can be considered as improvement to the location model, and alternatives to other classification methods particularly in handling mixed variables with large binary size