22,532 research outputs found
A unified framework for finding differentially expressed genes from microarray experiments
<p>Abstract</p> <p>Background</p> <p>This paper presents a unified framework for finding differentially expressed genes (DEGs) from the microarray data. The proposed framework has three interrelated modules: (i) gene ranking, ii) significance analysis of genes and (iii) validation. The first module uses two gene selection algorithms, namely, a) two-way clustering and b) combined adaptive ranking to rank the genes. The second module converts the gene ranks into p-values using an R-test and fuses the two sets of p-values using the Fisher's omnibus criterion. The DEGs are selected using the FDR analysis. The third module performs three fold validations of the obtained DEGs. The robustness of the proposed unified framework in gene selection is first illustrated using false discovery rate analysis. In addition, the clustering-based validation of the DEGs is performed by employing an adaptive subspace-based clustering algorithm on the training and the test datasets. Finally, a projection-based visualization is performed to validate the DEGs obtained using the unified framework.</p> <p>Results</p> <p>The performance of the unified framework is compared with well-known ranking algorithms such as t-statistics, Significance Analysis of Microarrays (SAM), Adaptive Ranking, Combined Adaptive Ranking and Two-way Clustering. The performance curves obtained using 50 simulated microarray datasets each following two different distributions indicate the superiority of the unified framework over the other reported algorithms. Further analyses on 3 real cancer datasets and 3 Parkinson's datasets show the similar improvement in performance. First, a 3 fold validation process is provided for the two-sample cancer datasets. In addition, the analysis on 3 sets of Parkinson's data is performed to demonstrate the scalability of the proposed method to multi-sample microarray datasets.</p> <p>Conclusion</p> <p>This paper presents a unified framework for the robust selection of genes from the two-sample as well as multi-sample microarray experiments. Two different ranking methods used in module 1 bring diversity in the selection of genes. The conversion of ranks to p-values, the fusion of p-values and FDR analysis aid in the identification of significant genes which cannot be judged based on gene ranking alone. The 3 fold validation, namely, robustness in selection of genes using FDR analysis, clustering, and visualization demonstrate the relevance of the DEGs. Empirical analyses on 50 artificial datasets and 6 real microarray datasets illustrate the efficacy of the proposed approach. The analyses on 3 cancer datasets demonstrate the utility of the proposed approach on microarray datasets with two classes of samples. The scalability of the proposed unified approach to multi-sample (more than two sample classes) microarray datasets is addressed using three sets of Parkinson's Data. Empirical analyses show that the unified framework outperformed other gene selection methods in selecting differentially expressed genes from microarray data.</p
Random lasso
We propose a computationally intensive method, the random lasso method, for
variable selection in linear models. The method consists of two major steps. In
step 1, the lasso method is applied to many bootstrap samples, each using a set
of randomly selected covariates. A measure of importance is yielded from this
step for each covariate. In step 2, a similar procedure to the first step is
implemented with the exception that for each bootstrap sample, a subset of
covariates is randomly selected with unequal selection probabilities determined
by the covariates' importance. Adaptive lasso may be used in the second step
with weights determined by the importance measures. The final set of covariates
and their coefficients are determined by averaging bootstrap results obtained
from step 2. The proposed method alleviates some of the limitations of lasso,
elastic-net and related methods noted especially in the context of microarray
data analysis: it tends to remove highly correlated variables altogether or
select them all, and maintains maximal flexibility in estimating their
coefficients, particularly with different signs; the number of selected
variables is no longer limited by the sample size; and the resulting prediction
accuracy is competitive or superior compared to the alternatives. We illustrate
the proposed method by extensive simulation studies. The proposed method is
also applied to a Glioblastoma microarray data analysis.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS377 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Variable selection for the multicategory SVM via adaptive sup-norm regularization
The Support Vector Machine (SVM) is a popular classification paradigm in
machine learning and has achieved great success in real applications. However,
the standard SVM can not select variables automatically and therefore its
solution typically utilizes all the input variables without discrimination.
This makes it difficult to identify important predictor variables, which is
often one of the primary goals in data analysis. In this paper, we propose two
novel types of regularization in the context of the multicategory SVM (MSVM)
for simultaneous classification and variable selection. The MSVM generally
requires estimation of multiple discriminating functions and applies the argmax
rule for prediction. For each individual variable, we propose to characterize
its importance by the supnorm of its coefficient vector associated with
different functions, and then minimize the MSVM hinge loss function subject to
a penalty on the sum of supnorms. To further improve the supnorm penalty, we
propose the adaptive regularization, which allows different weights imposed on
different variables according to their relative importance. Both types of
regularization automate variable selection in the process of building
classifiers, and lead to sparse multi-classifiers with enhanced
interpretability and improved accuracy, especially for high dimensional low
sample size data. One big advantage of the supnorm penalty is its easy
implementation via standard linear programming. Several simulated examples and
one real gene data analysis demonstrate the outstanding performance of the
adaptive supnorm penalty in various data settings.Comment: Published in at http://dx.doi.org/10.1214/08-EJS122 the Electronic
Journal of Statistics (http://www.i-journals.org/ejs/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.
Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically
An adaptive significance threshold criterion for massive multiple hypotheses testing
This research deals with massive multiple hypothesis testing. First regarding
multiple tests as an estimation problem under a proper population model, an
error measurement called Erroneous Rejection Ratio (ERR) is introduced and
related to the False Discovery Rate (FDR). ERR is an error measurement similar
in spirit to FDR, and it greatly simplifies the analytical study of error
properties of multiple test procedures. Next an improved estimator of the
proportion of true null hypotheses and a data adaptive significance threshold
criterion are developed. Some asymptotic error properties of the significant
threshold criterion is established in terms of ERR under distributional
assumptions widely satisfied in recent applications. A simulation study
provides clear evidence that the proposed estimator of the proportion of true
null hypotheses outperforms the existing estimators of this important parameter
in massive multiple tests. Both analytical and simulation studies indicate that
the proposed significance threshold criterion can provide a reasonable balance
between the amounts of false positive and false negative errors, thereby
complementing and extending the various FDR control procedures. S-plus/R code
is available from the author upon request.Comment: Published at http://dx.doi.org/10.1214/074921706000000392 in the IMS
Lecture Notes--Monograph Series
(http://www.imstat.org/publications/lecnotes.htm) by the Institute of
Mathematical Statistics (http://www.imstat.org
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