Effective affinities in microarray data

In the past couple of years several studies have shown that hybridization in Affymetrix DNA microarrays can be rather well understood on the basis of simple models of physical chemistry. In the majority of the cases a Langmuir isotherm was used to fit experimental data. Although there is a general consensus about this approach, some discrepancies between different studies are evident. For instance, some authors have fitted the hybridization affinities from the microarray fluorescent intensities, while others used affinities obtained from melting experiments in solution. The former approach yields fitted affinities that at first sight are only partially consistent with solution values. In this paper we show that this discrepancy exists only superficially: a sufficiently complete model provides effective affinities which are fully consistent with those fitted to experimental data. This link provides new insight on the relevant processes underlying the functioning of DNA microarrays.Comment: 8 pages, 6 figure

Predictive analysis of microarray data

Microarray gene expression data are analyzed by means of a Bayesian nonparametric model, with emphasis on prediction of future observables, yielding a method for selection of differentially expressed genes and a classifier

Nonlinear Dimension Reduction for Microarray Data

[Biomedical imaging

Microarray Data

JPEG and Excel data files for six siRNAs designed to silence Renilla luciferase transfected in Hela cells. For experimental details please see associated manuscript to be published in Cell Biology Education, 2006. A smaller data set and practice exercise are also included here

TmaDB: a repository for tissue microarray data

Background: Tissue microarray (TMA) technology has been developed to facilitate large, genome-scale molecular pathology studies. This technique provides a high-throughput method for analyzing a large cohort of clinical specimens in a single experiment thereby permitting the parallel analysis of molecular alterations ( at the DNA, RNA, or protein level) in thousands of tissue specimens. As a vast quantity of data can be generated in a single TMA experiment a systematic approach is required for the storage and analysis of such data. Description: To analyse TMA output a relational database ( known as TmaDB) has been developed to collate all aspects of information relating to TMAs. These data include the TMA construction protocol, experimental protocol and results from the various immunocytological and histochemical staining experiments including the scanned images for each of the TMA cores. Furthermore the database contains pathological information associated with each of the specimens on the TMA slide, the location of the various TMAs and the individual specimen blocks ( from which cores were taken) in the laboratory and their current status i.e. if they can be sectioned into further slides or if they are exhausted. TmaDB has been designed to incorporate and extend many of the published common data elements and the XML format for TMA experiments and is therefore compatible with the TMA data exchange specifications developed by the Association for Pathology Informatics community. Finally the design of the database is made flexible such that TMA experiments from several types of cancer can be stored in a single database, which incorporates the national minimum data set required for pathology reports supported by the Royal College of Pathologists (UK). Conclusion: TmaDB will provide a comprehensive repository for TMA data such that a large number of results from the numerous immunostaining experiments can be efficiently compared for each of the TMA cores. This will allow a systematic, large-scale comparison of tumour samples to facilitate the identification of gene products of clinical importance such as therapeutic or prognostic markers. In addition this work will contribute to the establishment of a standard for reporting TMA data analogous to MIAME in the description of microarray dat

Physics-based analysis of Affymetrix microarray data

We analyze publicly available data on Affymetrix microarrays spike-in experiments on the human HGU133 chipset in which sequences are added in solution at known concentrations. The spike-in set contains sequences of bacterial, human and artificial origin. Our analysis is based on a recently introduced molecular-based model [E. Carlon and T. Heim, Physica A 362, 433 (2006)] which takes into account both probe-target hybridization and target-target partial hybridization in solution. The hybridization free energies are obtained from the nearest-neighbor model with experimentally determined parameters. The molecular-based model suggests a rescaling that should result in a "collapse" of the data at different concentrations into a single universal curve. We indeed find such a collapse, with the same parameters as obtained before for the older HGU95 chip set. The quality of the collapse varies according to the probe set considered. Artificial sequences, chosen by Affymetrix to be as different as possible from any other human genome sequence, generally show a much better collapse and thus a better agreement with the model than all other sequences. This suggests that the observed deviations from the predicted collapse are related to the choice of probes or have a biological origin, rather than being a problem with the proposed model.Comment: 11 pages, 10 figure

Prevalence and Patterns of Microarray Data Sharing

Sharing research data is a cornerstone of science. Although many tools and policies exist to encourage data sharing, the prevalence with which datasets are shared is not well understood. We report our preliminary results on patterns of sharing microarray data in public databases.

The most comprehensive method for measuring occurrences of public data sharing is manual curation of research reports, since data sharing plans are usually communicated in free text within the body of an article. Our early findings from manual curation of 100 papers suggest that 30% of investigators publicly share their full microarray datasets. Of these, 70% of the datasets are deposited at NCBI's Gene Expression Omnibus (GEO) database, 20% at EBI's ArrayExpress, and 10% in smaller databases or lab or publisher websites.

Next, we supplemented this manual process with a rough automated estimate of data sharing prevalence. Using PubMed, we identified research articles with MeSH terms for both "Gene Expression Profiling" and "Oligonucleotide Array Sequence Analysis" and published in 2006. We then searched GEO and ArrayExpress for links to these PubMed IDs to determine which of the articles had been credited as an originating data source.

Of the 2503 articles, 440 (18%) articles had links from either GEO or ArrayExpress. Of these 440 articles, 70% had links from GEO and 30% from ArrayExpress, with an overlapping 12% from both GEO and ArrayExpress.

Interestingly, studies with free full text at PubMed were twice (Odds Ratio=2.1; 95% confidence interval: [1.7 to 2.5]) as likely to be linked as a data source within GEO or ArrayExpress than those without free full text. Studies with human data were less likely to have a link (OR=0.8 [0.6 to 0.9]) than studies with only non-human data. The proportion of articles with a link within these two databases has increased over time: the odds of a data-source link for studies was 2.5 [2.0 to 3.1] times greater for studies published in 2006 than 2002.

As might be expected, studies with the fewest funding sources had the fewest data-sharing links: only 28 (6%) of the 433 studies with no funding source were listed within GEO or ArrayExpress. In contrast, studies funded by the NIH, the US government, or a non-US government source had data-sharing links in 282 of 1556 cases (18%), while studies funded by two or more of these mechanisms were listed in the databases in 130 out of 514 cases (25%).

In summary, our initial manual approach for identifying studies which shared their data was comprehensive but time-consuming; natural language processing techniques could be helpful. Our subsequent automated approach yielded conservative estimates for total data sharing prevalence, nonetheless revealing several promising hypotheses for data sharing behavior

We hope these preliminary results will inspire additional investigations into data sharing behavior, and in turn the development of effective policies and tools to facilitate this important aspect of scientific research