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微阵列数据的噪声过滤和非参数分析突出了口腔癌、前列腺癌、肺癌、卵巢癌和乳腺癌的鉴别标志物。

Noise filtering and nonparametric analysis of microarray data underscores discriminating markers of oral, prostate, lung, ovarian and breast cancer.

作者信息

Aris Virginie M, Cody Michael J, Cheng Jeff, Dermody James J, Soteropoulos Patricia, Recce Michael, Tolias Peter P

机构信息

Center for Applied Genomics, Public Health Research Institute, Newark, NJ 07103, USA.

出版信息

BMC Bioinformatics. 2004 Nov 29;5:185. doi: 10.1186/1471-2105-5-185.

Abstract

BACKGROUND

A major goal of cancer research is to identify discrete biomarkers that specifically characterize a given malignancy. These markers are useful in diagnosis, may identify potential targets for drug development, and can aid in evaluating treatment efficacy and predicting patient outcome. Microarray technology has enabled marker discovery from human cells by permitting measurement of steady-state mRNA levels derived from thousands of genes. However many challenging and unresolved issues regarding the acquisition and analysis of microarray data remain, such as accounting for both experimental and biological noise, transcripts whose expression profiles are not normally distributed, guidelines for statistical assessment of false positive/negative rates and comparing data derived from different research groups. This study addresses these issues using Affymetrix HG-U95A and HG-U133 GeneChip data derived from different research groups.

RESULTS

We present here a simple non parametric approach coupled with noise filtering to identify sets of genes differentially expressed between the normal and cancer states in oral, breast, lung, prostate and ovarian tumors. An important feature of this study is the ability to integrate data from different laboratories, improving the analytical power of the individual results. One of the most interesting findings is the down regulation of genes involved in tissue differentiation.

CONCLUSIONS

This study presents the development and application of a noise model that suppresses noise, limits false positives in the results, and allows integration of results from individual studies derived from different research groups.

摘要

背景

癌症研究的一个主要目标是识别能够特异性表征特定恶性肿瘤的离散生物标志物。这些标志物在诊断中很有用,可识别药物开发的潜在靶点,并有助于评估治疗效果和预测患者预后。微阵列技术通过允许测量源自数千个基因的稳态mRNA水平,实现了从人类细胞中发现标志物。然而,关于微阵列数据的获取和分析仍存在许多具有挑战性且未解决的问题,例如如何处理实验噪声和生物噪声、表达谱呈非正态分布的转录本、假阳性/阴性率的统计评估指南以及比较来自不同研究组的数据。本研究使用来自不同研究组的Affymetrix HG-U95A和HG-U133基因芯片数据来解决这些问题。

结果

我们在此提出一种简单的非参数方法并结合噪声过滤,以识别口腔、乳腺、肺、前列腺和卵巢肿瘤中正常状态与癌症状态之间差异表达的基因集。本研究的一个重要特点是能够整合来自不同实验室的数据,提高单个结果的分析能力。最有趣的发现之一是参与组织分化的基因下调。

结论

本研究展示了一种噪声模型的开发与应用,该模型可抑制噪声、限制结果中的假阳性,并允许整合来自不同研究组的个体研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c760/538261/6e2c203f778d/1471-2105-5-185-1.jpg

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