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Analysis of discordant Affymetrix probesets casts serious doubt on idea of microarray data reutilization.

ABSTRACT: BACKGROUND: Affymetrix microarray technology allows one to investigate expression of thousands of genes simultaneously upon a variety of conditions. In a popular U133A microarray platform, the expression of 37% of genes is measured by more than one probeset. The discordant expression observed for two different probesets that match the same gene is a widespread phenomenon which is usually underestimated, ignored or disregarded. RESULTS: Here we evaluate the prevalence of discordant expression in data collected using Affymetrix HG-U133A microarray platform. In U133A, about 30% of genes annotated by two different probesets demonstrate a substantial correlation between independently measured expression values. To our surprise, sorting the probesets according to the nature of the discrepancy in their expression levels allowed the classification of the respective genes according to their fundamental functional properties, including observed enrichment by tissue-specific transcripts and alternatively spliced variants. On another hand, an absence of discrepancies in probesets that simultaneously match several different genes allowed us to pinpoint non-expressed pseudogenes and gene groups with highly correlated expression patterns. Nevertheless, in many cases, the nature of discordant expression of two probesets that match the same transcript remains unexplained. It is possible that these probesets report differently regulated sets of transcripts, or, in best case scenario, two different sets of transcripts that represent the same gene. CONCLUSION: The majority of absolute gene expression values collected using Affymetrix microarrays may not be suitable for typical interpretative downstream analysis.

SUBMITTER: Marakhonov A

PROVIDER: S-EPMC4303952 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Analysis of discordant Affymetrix probesets casts serious doubt on idea of microarray data reutilization.

Marakhonov Andrey A Sadovskaya Nataliya N Antonov Ivan I Baranova Ancha A Skoblov Mikhail M

BMC genomics 20141219

<h4>Background</h4>Affymetrix microarray technology allows one to investigate expression of thousands of genes simultaneously upon a variety of conditions. In a popular U133A microarray platform, the expression of 37% of genes is measured by more than one probeset. The discordant expression observed for two different probesets that match the same gene is a widespread phenomenon which is usually underestimated, ignored or disregarded.<h4>Results</h4>Here we evaluate the prevalence of discordant e ...[more]

PMID: 25563078

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Project description:BACKGROUND:Since 2010 the People's Republic of China has been engaged in an effort to reform its system of organ transplantation by developing a voluntary organ donation and allocation infrastructure. This has required a shift in the procurement of organs sourced from China's prison and security apparatus to hospital-based voluntary donors declared dead by neurological and/or circulatory criteria. Chinese officials announced that from January 1, 2015, hospital-based donors would be the sole source of organs. This paper examines the availability, transparency, integrity, and consistency of China's official transplant data. METHODS:Forensic statistical methods were used to examine key deceased organ donation datasets from 2010 to 2018. Two central-level datasets - published by the China Organ Transplant Response System (COTRS) and the Red Cross Society of China - are tested for evidence of manipulation, including conformance to simple mathematical formulae, arbitrary internal ratios, the presence of anomalous data artefacts, and cross-consistency. Provincial-level data in five regions are tested for coherence, consistency, and plausibility, and individual hospital data in those provinces are examined for consistency with provincial-level data. RESULTS:COTRS data conforms almost precisely to a mathematical formula (which first appeared to be a general quadratic, but with further confirmatory data was discovered to be a simpler one-parameter quadratic) while Central Red Cross data mirrors it, albeit imperfectly. The analysis of both datasets suggests human-directed data manufacture and manipulation. Contradictory, implausible, or anomalous data artefacts were found in five provincial datasets, suggesting that these data may have been manipulated to enforce conformity with central quotas. A number of the distinctive features of China's current organ procurement and allocation system are discussed, including apparent misclassification of nonvoluntary donors as voluntary. CONCLUSION:A variety of evidence points to what the authors believe can only be plausibly explained by systematic falsification and manipulation of official organ transplant datasets in China. Some apparently nonvoluntary donors also appear to be misclassified as voluntary. This takes place alongside genuine voluntary organ transplant activity, which is often incentivized by large cash payments. These findings are relevant for international interactions with China's organ transplantation system.

Dataset Information

Analysis of discordant Affymetrix probesets casts serious doubt on idea of microarray data reutilization.

Publications

Analysis of discordant Affymetrix probesets casts serious doubt on idea of microarray data reutilization.

Similar Datasets

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