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用于预测化学作用模式的基因表达数据的跨平台一致性

Inter-platform concordance of gene expression data for the prediction of chemical mode of action.

作者信息

Siriwardhana Chathura, Datta Susmita, Datta Somnath

机构信息

Office of Biostatistics & Quantitative Health Sciences, University of Hawaii John A. Burns School of Medicine, Honolulu, 96813, HI, USA.

Department of Biostatistics, University of Florida, Gainesville, 32603, FL, USA.

出版信息

Biol Direct. 2016 Dec 20;11(1):67. doi: 10.1186/s13062-016-0167-9.

Abstract

BACKGROUND

It is interesting to study the consistency of outcomes arising from two genomic platforms: Microarray and RNAseq, which are established on fundamentally different technologies. This topic has been frequently discussed from the prospect of comparing differentially expressed genes (DEGs). In this study, we explore the inter-platform concordance between microarray and RNASeq in their ability to classify samples based on genomic information. We use a set of 7 standard multi-class classifiers and an adaptive ensemble classifier developed around them to predict Chemical Modes of Actions (MOA) of data profiled by microarray and RNASeq platforms from Rat Liver samples exposed to a variety of chemical compounds. We study the concordance between microarray and RNASeq data in various forms, based on classifier's performance between two platforms.

RESULTS

Using an ensemble classifier we observe improved prediction performance compared to a set of standard classifiers. We discover a clear concordance between each individual classifier's performances in two genomic platforms. Additionally, we identify a set of important genes those specifies MOAs, by focusing on their impact on the classification and later we find that some of these top genes have direct associations with the presence of toxic compounds in the liver.

CONCLUSION

Overall there appears to be fair amount of concordance between the two platforms as far as classification is concerned. We observe widely different classification performances among individual classifiers, which reflect the unreliability of restricting to a single classifier in the case of high dimensional classification problems.

REVIEWERS

An extended abstract of this research paper was selected for the CAMDA Satellite Meeting to ISMB 2015 by the CAMDA Programme Committee. The full research paper then underwent two rounds of Open Peer Review under a responsible CAMDA Programme Committee member, Lan Hu, PhD (Bio-Rad Laboratories, Digital Biology Center-Cambridge). Open Peer Review was provided by Yiyi Liu and Partha Dey. The Reviewer Comments section shows the full reviews and author responses.

摘要

背景

研究基于根本不同技术建立的两个基因组平台——微阵列和RNA测序所产生结果的一致性很有意思。这个话题经常从比较差异表达基因(DEG)的角度进行讨论。在本研究中,我们探讨微阵列和RNA测序在基于基因组信息对样本进行分类能力方面的平台间一致性。我们使用一组7个标准多类分类器以及围绕它们开发的自适应集成分类器,来预测由微阵列和RNA测序平台对暴露于多种化合物的大鼠肝脏样本进行数据剖析后的化学作用模式(MOA)。我们基于两个平台间分类器的性能,研究微阵列和RNA测序数据在各种形式下的一致性。

结果

使用集成分类器,我们观察到与一组标准分类器相比,预测性能有所提高。我们发现两个基因组平台中每个单独分类器的性能之间存在明显的一致性。此外,我们通过关注它们对分类的影响,确定了一组指定MOA的重要基因,随后我们发现其中一些顶级基因与肝脏中有毒化合物的存在有直接关联。

结论

总体而言,就分类而言,两个平台之间似乎有相当程度的一致性。我们观察到各个分类器之间的分类性能差异很大,这反映了在高维分类问题中仅使用单个分类器的不可靠性。

评审

本研究论文的扩展摘要被CAMDA计划委员会选入2015年ISMB的CAMDA卫星会议。完整的研究论文随后在负责的CAMDA计划委员会成员Lan Hu博士(Bio-Rad Laboratories,数字生物学中心 - 剑桥)的主持下进行了两轮开放同行评审。开放同行评审由Yiyi Liu和Partha Dey提供。评审意见部分展示了完整的评审和作者回复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/695c/5168706/ddc2dd1e3e3f/13062_2016_167_Fig1_HTML.jpg

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