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Sharing and reusing gene expression profiling data in neuroscience.

ABSTRACT: As public availability of gene expression profiling data increases, it is natural to ask how these data can be used by neuroscientists. Here we review the public availability of high-throughput expression data in neuroscience and how it has been reused, and tools that have been developed to facilitate reuse. There is increasing interest in making expression data reuse a routine part of the neuroscience tool-kit, but there are a number of challenges. Data must become more readily available in public databases; efforts to encourage investigators to make data available are important, as is education on the benefits of public data release. Once released, data must be better-annotated. Techniques and tools for data reuse are also in need of improvement. Integration of expression profiling data with neuroscience-specific resources such as anatomical atlases will further increase the value of expression data.

SUBMITTER: Wan X

PROVIDER: S-EPMC2980754 | biostudies-other | 2007

REPOSITORIES: biostudies-other

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Sharing and reusing gene expression profiling data in neuroscience.

Wan Xiang X Pavlidis Paul P

Neuroinformatics 20070101 3

As public availability of gene expression profiling data increases, it is natural to ask how these data can be used by neuroscientists. Here we review the public availability of high-throughput expression data in neuroscience and how it has been reused, and tools that have been developed to facilitate reuse. There is increasing interest in making expression data reuse a routine part of the neuroscience tool-kit, but there are a number of challenges. Data must become more readily available in pub ...[more]

PMID: 17917127

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Project description:Multi-gene interactions likely play an important role in the development of complex phenotypes, and relationships between interacting genes pose a challenging statistical problem in microarray analysis, since the genes involved in these interactions may not exhibit marginal differential expression. As a result, it is necessary to develop tools that can identify sets of interacting genes that discriminate phenotypes without requiring that the classification boundary between phenotypes be convex.We describe an extension and application of a new unsupervised statistical learning technique, known as the Partition Decoupling Method (PDM), to gene expression microarray data. This method may be used to classify samples based on multi-gene expression patterns and to identify pathways associated with phenotype, without relying upon the differential expression of individual genes. The PDM uses iterated spectral clustering and scrubbing steps, revealing at each iteration progressively finer structure in the geometry of the data. Because spectral clustering has the ability to discern clusters that are not linearly separable, it is able to articulate relationships between samples that would be missed by distance- and tree-based classifiers. After projecting the data onto the cluster centroids and computing the residuals ("scrubbing"), one can repeat the spectral clustering, revealing clusters that were not discernible in the first layer. These iterations, each of which provide a partition of the data that is decoupled from the others, are carried forward until the structure in the residuals is indistinguishable from noise, preventing over-fitting. We describe the PDM in detail and apply it to three publicly available cancer gene expression data sets. By applying the PDM on a pathway-by-pathway basis and identifying those pathways that permit unsupervised clustering of samples that match known sample characteristics, we show how the PDM may be used to find sets of mechanistically-related genes that may play a role in disease. An R package to carry out the PDM is available for download.We show that the PDM is a useful tool for the analysis of gene expression data from complex diseases, where phenotypes are not linearly separable and multi-gene effects are likely to play a role. Our results demonstrate that the PDM is able to distinguish cell types and treatments with higher accuracy than is obtained through other approaches, and that the Pathway-PDM application is a valuable technique for identifying disease-associated pathways.

Project description:BackgroundWith the increasing number of expression profiling technologies, researchers today are confronted with choosing the technology that has sufficient power with minimal sample size, in order to reduce cost and time. These depend on data variability, partly determined by sample type, preparation and processing. Objective measures that help experimental design, given own pilot data, are thus fundamental.ResultsRelative power and sample size analysis were performed on two distinct data sets. The first set consisted of Affymetrix array data derived from a nutrigenomics experiment in which weak, intermediate and strong PPARalpha agonists were administered to wild-type and PPARalpha-null mice. Our analysis confirms the hierarchy of PPARalpha-activating compounds previously reported and the general idea that larger effect sizes positively contribute to the average power of the experiment. A simulation experiment was performed that mimicked the effect sizes seen in the first data set. The relative power was predicted but the estimates were slightly conservative. The second, more challenging, data set describes a microarray platform comparison study using hippocampal deltaC-doublecortin-like kinase transgenic mice that were compared to wild-type mice, which was combined with results from Solexa/Illumina deep sequencing runs. As expected, the choice of technology greatly influences the performance of the experiment. Solexa/Illumina deep sequencing has the highest overall power followed by the microarray platforms Agilent and Affymetrix. Interestingly, Solexa/Illumina deep sequencing displays comparable power across all intensity ranges, in contrast with microarray platforms that have decreased power in the low intensity range due to background noise. This means that deep sequencing technology is especially more powerful in detecting differences in the low intensity range, compared to microarray platforms.ConclusionPower and sample size analysis based on pilot data give valuable information on the performance of the experiment and can thereby guide further decisions on experimental design. Solexa/Illumina deep sequencing is the technology of choice if interest lies in genes expressed in the low-intensity range. Researchers can get guidance on experimental design using our approach on their own pilot data implemented as a BioConductor package, SSPA http://bioconductor.org/packages/release/bioc/html/SSPA.html.

Dataset Information

Sharing and reusing gene expression profiling data in neuroscience.

Publications

Sharing and reusing gene expression profiling data in neuroscience.

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