Dataset Information

Ratio adjustment and calibration scheme for gene-wise normalization to enhance microarray inter-study prediction.

ABSTRACT:

Motivation

Reproducibility analyses of biologically relevant microarray studies have mostly focused on overlap of detected biomarkers or correlation of differential expression evidences across studies. For clinical utility, direct inter-study prediction (i.e. to establish a prediction model in one study and apply to another) for disease diagnosis or prognosis prediction is more important. Normalization plays a key role for such a task. Traditionally, sample-wise normalization has been a standard for inter-array and inter-study normalization. For gene-wise normalization, it has been implemented for intra-study or inter-study predictions in a few papers while its rationale, strategy and effect remain unexplored.

Results

In this article, we investigate the effect of gene-wise normalization in microarray inter-study prediction. Gene-specific intensity discrepancies across studies are commonly found even after proper sample-wise normalization. We explore the rationale and necessity of gene-wise normalization. We also show that the ratio of sample sizes in normal versus diseased groups can greatly affect the performance of gene-wise normalization and an analytical method is developed to adjust for the imbalanced ratio effect. Both simulation results and applications to three lung cancer and two prostate cancer data sets, considering both binary classification and survival risk predictions, showed significant and robust improvement of the new adjustment. A calibration scheme is developed to apply the ratio-adjusted gene-wise normalization for prospective clinical trials. The number of calibration samples needed is estimated from existing studies and suggested for future applications. The result has important implication to the translational research of microarray as a practical disease diagnosis and prognosis prediction tool.

SUBMITTER: Cheng C

PROVIDER: S-EPMC2732320 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ratio adjustment and calibration scheme for gene-wise normalization to enhance microarray inter-study prediction.

Cheng Chunrong C Shen Kui K Song Chi C Luo Jianhua J Tseng George C GC

Bioinformatics (Oxford, England) 20090504 13

<h4>Motivation</h4>Reproducibility analyses of biologically relevant microarray studies have mostly focused on overlap of detected biomarkers or correlation of differential expression evidences across studies. For clinical utility, direct inter-study prediction (i.e. to establish a prediction model in one study and apply to another) for disease diagnosis or prognosis prediction is more important. Normalization plays a key role for such a task. Traditionally, sample-wise normalization has been a ...[more]

PMID: 19414534

Similar Datasets

Project description:BACKGROUND: Genome context methods have been introduced in the last decade as automatic methods to predict functional relatedness between genes in a target genome using the patterns of existence and relative locations of the homologs of those genes in a set of reference genomes. Much work has been done in the application of these methods to different bioinformatics tasks, but few papers present a systematic study of the methods and their combination necessary for their optimal use. RESULTS: We present a thorough study of the four main families of genome context methods found in the literature: phylogenetic profile, gene fusion, gene cluster, and gene neighbor. We find that for most organisms the gene neighbor method outperforms the phylogenetic profile method by as much as 40% in sensitivity, being competitive with the gene cluster method at low sensitivities. Gene fusion is generally the worst performing of the four methods. A thorough exploration of the parameter space for each method is performed and results across different target organisms are presented. We propose the use of normalization procedures as those used on microarray data for the genome context scores. We show that substantial gains can be achieved from the use of a simple normalization technique. In particular, the sensitivity of the phylogenetic profile method is improved by around 25% after normalization, resulting, to our knowledge, on the best-performing phylogenetic profile system in the literature. Finally, we show results from combining the various genome context methods into a single score. When using a cross-validation procedure to train the combiners, with both original and normalized scores as input, a decision tree combiner results in gains of up to 20% with respect to the gene neighbor method. Overall, this represents a gain of around 15% over what can be considered the state of the art in this area: the four original genome context methods combined using a procedure like that used in the STRING database. Unfortunately, we find that these gains disappear when the combiner is trained only with organisms that are phylogenetically distant from the target organism. CONCLUSIONS: Our experiments indicate that gene neighbor is the best individual genome context method and that gains from the combination of individual methods are very sensitive to the training data used to obtain the combiner's parameters. If adequate training data is not available, using the gene neighbor score by itself instead of a combined score might be the best choice.

Dataset Information

Ratio adjustment and calibration scheme for gene-wise normalization to enhance microarray inter-study prediction.

Motivation

Results

Publications

Ratio adjustment and calibration scheme for gene-wise normalization to enhance microarray inter-study prediction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets