Dataset Information

BreastMark: an integrated approach to mining publicly available transcriptomic datasets relating to breast cancer outcome.

ABSTRACT: INTRODUCTION: Breast cancer is a complex heterogeneous disease for which a substantial resource of transcriptomic data is available. Gene expression data have facilitated the division of breast cancer into, at least, five molecular subtypes, namely luminal A, luminal B, HER2, normal-like and basal. Once identified, breast cancer subtypes can inform clinical decisions surrounding patient treatment and prognosis. Indeed, it is important to identify patients at risk of developing aggressive disease so as to tailor the level of clinical intervention. METHODS: We have developed a user-friendly, web-based system to allow the evaluation of genes/microRNAs (miRNAs) that are significantly associated with survival in breast cancer and its molecular subtypes. The algorithm combines gene expression data from multiple microarray experiments which frequently also contain miRNA expression information, and detailed clinical data to correlate outcome with gene/miRNA expression levels. This algorithm integrates gene expression and survival data from 26 datasets on 12 different microarray platforms corresponding to approximately 17,000 genes in up to 4,738 samples. In addition, the prognostic potential of 341 miRNAs can be analysed. RESULTS: We demonstrated the robustness of our approach in comparison to two commercially available prognostic tests, oncotype DX and MammaPrint. Our algorithm complements these prognostic tests and is consistent with their findings. In addition, BreastMark can act as a powerful reductionist approach to these more complex gene signatures, eliminating superfluous genes, potentially reducing the cost and complexity of these multi-index assays. Known miRNA prognostic markers, mir-205 and mir-93, were used to confirm the prognostic value of this tool in a miRNA setting. We also applied the algorithm to examine expression of 58 receptor tyrosine kinases in the basal-like subtype, identifying six receptor tyrosine kinases associated with poor disease-free survival and/or overall survival (EPHA5, FGFR1, FGFR3, VEGFR1, PDGFR?, and TIE1). A web application for using this algorithm is currently available. CONCLUSIONS: BreastMark is a powerful tool for examining putative gene/miRNA prognostic markers in breast cancer. The value of this tool will be in the preliminary assessment of putative biomarkers in breast cancer. It will be of particular use to research groups with limited bioinformatics facilities.

SUBMITTER: Madden SF

PROVIDER: S-EPMC3978487 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BreastMark: an integrated approach to mining publicly available transcriptomic datasets relating to breast cancer outcome.

Madden Stephen F SF Clarke Colin C Gaule Patricia P Aherne Sinead T ST O'Donovan Norma N Clynes Martin M Crown John J Gallagher William M WM

Breast cancer research : BCR 20130101 4

<h4>Introduction</h4>Breast cancer is a complex heterogeneous disease for which a substantial resource of transcriptomic data is available. Gene expression data have facilitated the division of breast cancer into, at least, five molecular subtypes, namely luminal A, luminal B, HER2, normal-like and basal. Once identified, breast cancer subtypes can inform clinical decisions surrounding patient treatment and prognosis. Indeed, it is important to identify patients at risk of developing aggressive ...[more]

PMID: 23820017

Similar Datasets

Project description:Prostate cancer (PCa) is the second most common cancer in men, and the second leading cause of death from cancer in men. Many studies on PCa have been carried out, each taking much time before the data is collected and ready to be analyzed. However, on the internet there is already a wide range of PCa datasets available, which could be used for data mining, predictive modelling or other purposes, reducing the need to setup new studies to collect data. In the current scientific climate, moving more and more to the analysis of "big data" and large, international, multi-site projects using a modern IT infrastructure, these datasets could be proven extremely valuable. This review presents an overview of publicly available patient-centered PCa datasets, divided into three categories (clinical, genomics and imaging) and an "overall" section to enable researchers to select a suitable dataset for analysis, without having to go through days of work to find the right data. To acquire a list of human PCa databases, scientific literature databases and academic social network sites were searched. We also used the information from other reviews. All databases in the combined list were then checked for public availability. Only databases that were either directly publicly available or available after signing a research data agreement or retrieving a free login were selected for inclusion in this review. Data should be available to commercial parties as well. This paper focuses on patient-centered data, so the genomics data section does not include gene-centered databases or pathway-centered databases. We identified 42 publicly available, patient-centered PCa datasets. Some of these consist of different smaller datasets. Some of them contain combinations of datasets from the three data domains: clinical data, imaging data and genomics data. Only one dataset contains information from all three domains. This review presents all datasets and their characteristics: number of subjects, clinical fields, imaging modalities, expression data, mutation data, biomarker measurements, etc. Despite all the attention that has been given to making this overview of publicly available databases as extensive as possible, it is very likely not complete, and will also be outdated soon. However, this review might help many PCa researchers to find suitable datasets to answer the research question with, without the need to start a new data collection project. In the coming era of big data analysis, overviews like this are becoming more and more useful.

Project description:IntroductionMicroarray analysis has revolutionized the role of genomic prognostication in breast cancer. However, most studies are single series studies, and suffer from methodological problems. We sought to use a meta-analytic approach in combining multiple publicly available datasets, while correcting for batch effects, to reach a more robust oncogenomic analysis.AimThe aim of the present study was to find gene sets associated with distant metastasis free survival (DMFS) in systemically untreated, node-negative breast cancer patients, from publicly available genomic microarray datasets.MethodsFour microarray series (having 742 patients) were selected after a systematic search and combined. Cox regression for each gene was done for the combined dataset (univariate, as well as multivariate - adjusted for expression of Cell cycle related genes) and for the 4 major molecular subtypes. The centre and microarray batch effects were adjusted by including them as random effects variables. The Cox regression coefficients for each analysis were then ranked and subjected to a Gene Set Enrichment Analysis (GSEA).ResultsGene sets representing protein translation were independently negatively associated with metastasis in the Luminal A and Luminal B subtypes, but positively associated with metastasis in Basal tumors. Proteinaceous extracellular matrix (ECM) gene set expression was positively associated with metastasis, after adjustment for expression of cell cycle related genes on the combined dataset. Finally, the positive association of the proliferation-related genes with metastases was confirmed.ConclusionTo the best of our knowledge, the results depicting mixed prognostic significance of protein translation in breast cancer subtypes are being reported for the first time. We attribute this to our study combining multiple series and performing a more robust meta-analytic Cox regression modeling on the combined dataset, thus discovering 'hidden' associations. This methodology seems to yield new and interesting results and may be used as a tool to guide new research.

Project description:Background: Antibiotics are often prescribed empirically to treat infection syndromes before causative bacteria and their susceptibility to antibiotics are identified. Guidelines on empiric antibiotic prescribing are key to effective treatment of infection syndromes, and need to be informed by likely bacterial aetiology and antibiotic resistance patterns. We aimed to create a clinically-relevant composite index of antibiotic resistance for common infection syndromes to inform recommendations at the national level. Methods: To create our index, we used open-access antimicrobial resistance (AMR) surveillance datasets, including the ECDC Surveillance Atlas, CDDEP ResistanceMap, WHO GLASS and the newly-available Pfizer ATLAS dataset. We integrated these with data on aetiology of common infection syndromes, existing empiric prescribing guidelines, and pricing and availability of antibiotics. Results: The ATLAS dataset covered many more bacterial species (287) and antibiotics (52) than other datasets (ranges = 8-11 and 16-32 respectively), but had a similar number of samples per country per year. Using these data, we were able to make empiric prescribing recommendations for bloodstream infection, pneumonia and cellulitis/skin abscess in up to 44 countries. There was insufficient data to make national-level recommendations for the other six syndromes investigated. Results are presented in an interactive web app, where users can visualise underlying resistance proportions to first-line empiric antibiotics for infection syndromes and countries of interest. Conclusions: We found that whilst the creation of a composite resistance index for empiric antibiotic therapy was technically feasible, the ATLAS dataset in its current form can only inform on a limited number of infection syndromes. Other open-access AMR surveillance datasets are largely limited to bloodstream infection specimens and cannot directly inform treatment of other syndromes. With improving availability of international AMR data and better understanding of infection aetiology, this approach may prove useful for informing empiric prescribing decisions in settings with limited local AMR surveillance data.

Dataset Information

BreastMark: an integrated approach to mining publicly available transcriptomic datasets relating to breast cancer outcome.

Publications

BreastMark: an integrated approach to mining publicly available transcriptomic datasets relating to breast cancer outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets