Director, Technology Alliances ThoughtSpot. Stable predictive models across studies can only be expected if the phenotype to be predicted shows a low IR Type 1 classification , whereas for other phenotypes the biomarker stability may be insufficient. Microarrays measuring differential gene expression are widely used and should be versatile predictors of disease and other phenotypic data. As the impact of sample size variation may depend on the dimensionality of the differential expression pattern, Type 2 and 3 classifications will benefit significantly less from increased sample sizes, which can be seen in typical clinical studies. You consent to receiving marketing messages from Indeed and may opt from receiving such messages by following the unsubscribe link in our messages, or as detailed in our terms.

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It has been observed that biomarkers selected from different studies may not match when sample numbers are too small. Data sets used for this study with ArrayExpress identifiers, literature references and available meta data. Identifying stable gene lists for diagnosis, prognosis prediction, and treatment guidance of tumors remains a major challenge in cancer research. Differentially expressed genes are ordered by the p-value of a Bmd t-test statistic mbc 31 ].

Published online Oct Identification of stable gene expression signatures can facilitate the classification of clinical phenotypes and their associated physiological states.

This is in contrast to the distribution between grade 1 versus grade 2 tumors. This correlates with a Type 1 genome-wide differential expression pattern where the resulting distribution is dependent on the study design. Here we present a method to demonstrate that gene list stability and predictive power depends not only on the size of studies, but also on the clinical phenotype.


Dimension reduction for high-dimensional data. We demonstrate that the IR is indicative of biomarker stability: Plot of subspace dimensionality against IR. Various methods can be used to identify large scale patterns that comprise genomic subspaces.

Moreover, the qualitative heterogeneity of the genome-wide information distribution across different studies for high IR phenotypes indicate that biomarkers which are identified using ranked gene lists, will most likely not be predictive through statistical approaches alone.

Quantifying stability in gene list ranking across microarray derived clinical biomarkers

City, state, or zip code. The expression data was transformed to log 2 values. Many studies rely on microarrays to determine which genes are predominantly vmc of clinical cancer phenotypes or prognosis.

Therefore, a method to quantitatively translate results from lab experiments into clinical settings can be useful. Low IR values are obtained for e.

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For details on methods and results see additional file 1: Dallas, Texas – Column Group. For ER positive vs. Each dot represents the mean loss of accuracy for all studies bcm compared to the biomarker source study accuracy.

Unfortunately, highly desirable predictive gene lists, such as those which can elucidate the prognosis of individual relapses, belong to the classification with high IR values.

This result seems to depend only on the type of classification and not on the phenotype. Each eigenvector k represents a metagene whose expression X k, l in each tissue l is given by the weighted sum of the contribution of all genes j to the eigenvector:. We used the SVM as a classification machine with a bkc basis kernel. In case several probe sets share the same gene symbol, the probe set with the largest mean expression over all samples was used as representative for that symbol.


Hence, for each gene and combination of phenotype and study there are two p-values. However, phenotypes associated with lower IR values show more stability and transferability between heterogeneous studies.

While significant progress has been made in understanding genetic, molecular, behavioral, and neurological aspects of AD, relatively little is known about which environmental factors are important in AD etiology and how they interact with genetic factors in the development of AD.


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Our motivation in this study was to determine when stable predictive biomarkers can be identified from multiple microarray studies or meta-analyses. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies.

The projection lp p blue crosses onto S n shows similar p-values compared to the residuals lp r red crosses. Analysis of gene ranking stability 9436 relation to the IR For classification of clinical samples based on microarray data, prediction is usually performed with a gene list, a subset of all available genes.