Too much data, but little inter-changeability: a lesson learned from mining public data on tissue specificity of gene expression

BACKGROUND: The tissue expression pattern of a gene often provides an important clue to its potential role in a biological process. A vast amount of gene expression data have been and are being accumulated in public repository through different technology platforms. However, exploitations of these rich data sources remain limited in part due to issues of technology standardization. Our objective is to test the data comparability between SAGE and microarray technologies, through examining the expression pattern of genes under normal physiological states across variety of tissues. RESULTS: There are 42–54% of genes showing significant correlations in tissue expression patterns between SAGE and GeneChip, with 30–40% of genes whose expression patterns are positively correlated and 10–15% of genes whose expression patterns are negatively correlated at a statistically significant level (p = 0.05). Our analysis suggests that the discrepancy on the expression patterns derived from technology platforms is not likely from the heterogeneity of tissues used in these technologies, or other spurious correlations resulting from microarray probe design, abundance of genes, or gene function. The discrepancy can be partially explained by errors in the original assignment of SAGE tags to genes due to the evolution of sequence databases. In addition, sequence analysis has indicated that many SAGE tags and Affymetrix array probe sets are mapped to different splice variants or different sequence regions although they represent the same gene, which also contributes to the observed discrepancies between SAGE and array expression data. CONCLUSION: To our knowledge, this is the first report attempting to mine gene expression patterns across tissues using public data from different technology platforms. Unlike previous similar studies that only demonstrated the discrepancies between the two gene expression platforms, we carried out in-depth analysis to further investigate the cause for such discrepancies. Our study shows that the exploitation of rich public expression resource requires extensive knowledge about the technologies, and experiment. Informatic methodologies for better interoperability among platforms still remain a gap. One of the areas that can be improved practically is the accurate sequence mapping of SAGE tags and array probes to full-length genes. REVIEWERS: This article was reviewed by Dr. I. King Jordan, Dr. Joel Bader, and Dr. Arcady Mushegian

Comparative analysis and integrative classification of NCI60 cell lines and primary tumors using gene expression profiling data

BACKGROUND: NCI60 cell lines are derived from cancers of 9 tissue origins and have been invaluable in vitro models for cancer research and anti-cancer drug screen. Although extensive studies have been carried out to assess the molecular features of NCI60 cell lines related to cancer and their sensitivities to more than 100,000 chemical compounds, it remains unclear if and how well these cell lines represent or model their tumor tissues of origin. Identification and confirmation of correct origins of NCI60 cell lines are critical to their usage as model systems and to translate in vitro studies into clinical potentials. Here we report a direct comparison between NCI60 cell lines and primary tumors by analyzing global gene expression profiles. RESULTS: Comparative analysis suggested that 51 of 59 cell lines we analyzed represent their presumed tumors of origin. Taking advantage of available clinical information of primary tumor samples used to generate gene expression profiling data, we further classified those cell lines with the correct origins into different subtypes of cancer or different stages in cancer development. For example, 6 of 7 non-small cell lung cancer cell lines were classified as lung adenocarcinomas and all of them were classified into late stages in tumor progression. CONCLUSION: Taken together, we developed and applied a novel approach for systematic comparative analysis and integrative classification of NCI60 cell lines and primary tumors. Our results could provide guidance to the selection of appropriate cell lines for cancer research and pharmaceutical compound screenings. Moreover, this gene expression profile based approach can be generally applied to evaluate experimental model systems such as cell lines and animal models for human diseases

The effectiveness of treatments for Kashin–Beck disease: a systematic review and network meta-analysis

Objectives: This study aims to evaluate the efficacy of treatments for Kashin–Beck disease (KBD). Method: We searched PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, SinoMed, Chinese National Knowledge Infrastructure, reference lists and published systematic reviews and registries of ongoing trials through May 2015 for randomised controlled trials (RCTs) of treatments for KBD. Outcomes of interest were pain, function, stiffness, overall clinical improvement, radiographic improvement (X-ray) and adverse events. Frequentist network meta-analyses were conducted using random-effects consistency model to assess the efficacy of treatments for KBD. Results: Forty-four RCTs with 9815 participants were included in the review. In children or adolescents, selenium (risk ratio 1.88, 95% confidence interval (CI) 1.51–2.33), vitamin C (2.03, 1.40–2.95) and aspirin (2.14, 1.12–4.08) were effective for radiographic structure improvement. In adults, chondroitin plus glucosamine was the best for pain (standardised mean difference 1.46, 95% CI 1.07–1.85), followed by intra-articular injection of hyaluronic acid (IAH) (1.09, 0.70–1.48), chondroitin (0.84, 0.47–1.21), diclofenac (0.63, 1.18–1.08), naproxen (0.55, 0.12–0.98), meloxicam (0.52, 0.03–1.01) and glucosamine (0.40, 0.13–0.67) compared to placebo, with similar results for other clinical outcomes in adults. However, the strength of most evidence was limited by the small number of trials with low to moderate quality. Conclusions: Selenium supplement has demonstrated some benefits for structural improvement of the disease in children. Chondroitin, glucosamine, IAH and nonsteroid anti-inflammatory drugs are effective for symptom improvements of KBD in adults. Evidence of surgical and complementary treatments for symptoms and aspirin and vitamin C for structure has yet to be established.Key Points• There were 23 nutraceuticals, pharmaceuticals and surgical and complementary treatments assessed for Kashin–Beck disease (KBD) in randomised trials.• Among the 23 treatments, chondroitin, glucosamine, IAH and non-steroid anti-inflammatory drugs are more effective than placebo to relieve symptoms for adults with KBD.• Selenium supplement is more effective than placebo for radiographic improvement in children or adolescents.• The efficacy of surgeries, aspirin, vitamin C and complementary treatments for KBD has not been established yet

Biology Direct BioMed Central

Too much data, but little inter-changeability: a lesson learned from mining public data on tissue specificity of gene expressio