5,072 research outputs found
PLS dimension reduction for classification of microarray data
PLS dimension reduction is known to give good prediction accuracy in the context of classification with high-dimensional microarray data. In this paper, PLS is compared with some of the best state-of-the-art classification methods. In addition, a simple procedure to choose the number of components is suggested. The connection between PLS dimension reduction and gene selection is examined and a property of the first PLS component for binary classification is proven. PLS can also be used as a visualization tool for high-dimensional data in the classification framework. The whole study is based on 9 real microarray cancer data sets
Use of pre-transformation to cope with outlying values in important candidate genes
Outlying values in predictors often strongly affect the results of statistical analyses in high-dimensional settings. Although they frequently occur with most high-throughput techniques, the problem is often ignored in the literature. We suggest to use a very simple transformation, proposed before in a different context by Royston and Sauerbrei, as an intermediary step between array normalization and high-level statistical analysis. This straightforward univariate transformation identifies extreme values and reduces the influence of outlying values considerably in all further steps of statistical analysis without eliminating the incriminated observation or feature. The use of the transformation and its effects are demonstrated for diverse univariate and multivariate statistical analyses using nine publicly available microarray data sets
Boosting the concordance index for survival data - a unified framework to derive and evaluate biomarker combinations
The development of molecular signatures for the prediction of time-to-event
outcomes is a methodologically challenging task in bioinformatics and
biostatistics. Although there are numerous approaches for the derivation of
marker combinations and their evaluation, the underlying methodology often
suffers from the problem that different optimization criteria are mixed during
the feature selection, estimation and evaluation steps. This might result in
marker combinations that are only suboptimal regarding the evaluation criterion
of interest. To address this issue, we propose a unified framework to derive
and evaluate biomarker combinations. Our approach is based on the concordance
index for time-to-event data, which is a non-parametric measure to quantify the
discrimatory power of a prediction rule. Specifically, we propose a
component-wise boosting algorithm that results in linear biomarker combinations
that are optimal with respect to a smoothed version of the concordance index.
We investigate the performance of our algorithm in a large-scale simulation
study and in two molecular data sets for the prediction of survival in breast
cancer patients. Our numerical results show that the new approach is not only
methodologically sound but can also lead to a higher discriminatory power than
traditional approaches for the derivation of gene signatures.Comment: revised manuscript - added simulation study, additional result
Predicting Genetic Regulatory Response Using Classification
We present a novel classification-based method for learning to predict gene
regulatory response. Our approach is motivated by the hypothesis that in simple
organisms such as Saccharomyces cerevisiae, we can learn a decision rule for
predicting whether a gene is up- or down-regulated in a particular experiment
based on (1) the presence of binding site subsequences (``motifs'') in the
gene's regulatory region and (2) the expression levels of regulators such as
transcription factors in the experiment (``parents''). Thus our learning task
integrates two qualitatively different data sources: genome-wide cDNA
microarray data across multiple perturbation and mutant experiments along with
motif profile data from regulatory sequences. We convert the regression task of
predicting real-valued gene expression measurement to a classification task of
predicting +1 and -1 labels, corresponding to up- and down-regulation beyond
the levels of biological and measurement noise in microarray measurements. The
learning algorithm employed is boosting with a margin-based generalization of
decision trees, alternating decision trees. This large-margin classifier is
sufficiently flexible to allow complex logical functions, yet sufficiently
simple to give insight into the combinatorial mechanisms of gene regulation. We
observe encouraging prediction accuracy on experiments based on the Gasch S.
cerevisiae dataset, and we show that we can accurately predict up- and
down-regulation on held-out experiments. Our method thus provides predictive
hypotheses, suggests biological experiments, and provides interpretable insight
into the structure of genetic regulatory networks.Comment: 8 pages, 4 figures, presented at Twelfth International Conference on
Intelligent Systems for Molecular Biology (ISMB 2004), supplemental website:
http://www.cs.columbia.edu/compbio/geneclas
Statistical methods for tissue array images - algorithmic scoring and co-training
Recent advances in tissue microarray technology have allowed
immunohistochemistry to become a powerful medium-to-high throughput analysis
tool, particularly for the validation of diagnostic and prognostic biomarkers.
However, as study size grows, the manual evaluation of these assays becomes a
prohibitive limitation; it vastly reduces throughput and greatly increases
variability and expense. We propose an algorithm - Tissue Array Co-Occurrence
Matrix Analysis (TACOMA) - for quantifying cellular phenotypes based on
textural regularity summarized by local inter-pixel relationships. The
algorithm can be easily trained for any staining pattern, is absent of
sensitive tuning parameters and has the ability to report salient pixels in an
image that contribute to its score. Pathologists' input via informative
training patches is an important aspect of the algorithm that allows the
training for any specific marker or cell type. With co-training, the error rate
of TACOMA can be reduced substantially for a very small training sample (e.g.,
with size 30). We give theoretical insights into the success of co-training via
thinning of the feature set in a high-dimensional setting when there is
"sufficient" redundancy among the features. TACOMA is flexible, transparent and
provides a scoring process that can be evaluated with clarity and confidence.
In a study based on an estrogen receptor (ER) marker, we show that TACOMA is
comparable to, or outperforms, pathologists' performance in terms of accuracy
and repeatability.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS543 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Multi-test Decision Tree and its Application to Microarray Data Classification
Objective:
The desirable property of tools used to investigate biological data is
easy to understand models and predictive decisions.
Decision trees are particularly promising in this regard due to their comprehensible nature that resembles the hierarchical process of human decision making. However, existing algorithms for learning decision trees have tendency to underfit gene expression data. The main aim of this work is to improve the performance and stability of decision trees with only a small increase in their complexity.
Methods:
We propose a multi-test decision tree (MTDT); our main contribution is the application of several univariate tests in each non-terminal node of the decision tree. We also search for alternative, lower-ranked features in order to obtain more stable and reliable predictions.
Results:
Experimental validation was performed on several real-life gene expression datasets. Comparison results with eight classifiers show that MTDT has a statistically significantly higher accuracy than popular decision tree classifiers, and it was highly competitive with ensemble learning algorithms. The proposed solution managed to outperform its baseline algorithm on datasets by an average percent. A study performed on one of the datasets showed that the discovered genes used in the MTDT classification model
are supported by biological evidence in the literature.
Conclusion:
This paper introduces a new type of decision tree which is more suitable for solving biological problems.
MTDTs are relatively easy to analyze and much more powerful in modeling high dimensional microarray data than their popular counterparts
Stable Feature Selection for Biomarker Discovery
Feature selection techniques have been used as the workhorse in biomarker
discovery applications for a long time. Surprisingly, the stability of feature
selection with respect to sampling variations has long been under-considered.
It is only until recently that this issue has received more and more attention.
In this article, we review existing stable feature selection methods for
biomarker discovery using a generic hierarchal framework. We have two
objectives: (1) providing an overview on this new yet fast growing topic for a
convenient reference; (2) categorizing existing methods under an expandable
framework for future research and development
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