Reproducibility enhancement and differential expression of non predefined functional gene sets in human genome.

Reproducibility enhancement and differential expression of non predefined functional gene sets in human genome.
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DOI:
10.1186/1471-2164-15-1181
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发表时间:
2014-12-24
期刊:
影响因子:
4.4
通讯作者:
de Almeida RM
de Almeida RM
中科院分区:
生物学2区
文献类型:
--
作者:
da Silva SR;Perrone GC;Dinis JM;de Almeida RM

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转录谱分析是一种在全基因组范围内呈现和分析转录数据的方法,其减少了噪音并促进了生物学解释。产生有序基因列表,使得基因在功能上相关联的概率随着它们在列表上的距离而指数衰减。这个列表呈现了一个生物学逻辑,通过基因本体论术语或KEGG途径选择性地富集连续间隔来证明。转录图是通过取该列表上相邻基因的基因表达平均值获得的表达谱。转录图增强了功能相关基因集表达测量的重现性和精确度。在这里,我们提出了一个排序列表的智人和转录谱分析方法应用于不同的数据集。我们表明这种方法提高了实验重现性并增强了信号。我们将该方法应用于Hwang及其合作者的糖尿病研究,该研究侧重于通过糖尿病供体的线粒体与骨肉瘤细胞系(线粒体耗尽)杂交产生的胞质杂交体之间的表达差异。我们发现转录图方法揭示了与血液凝固和伤口愈合途径相关的基因组中的显著差异表达,以及不代表任何代谢途径或基因本体论术语的基因组。这些基因集与ECM-受体相互作用和分泌蛋白质有关。转录谱分析方法提供了一种自动化的方法来定义具有相关表达的基因组,减少全基因组转录谱中的噪声,并提高测量的重现性和灵敏度。这些优势使生物学解释,并指出差异表达的基因集在糖尿病,这是以前没有定义。本文的在线版本(doi:10.1186/1471-2164-15-1181)包含补充材料,可供授权用户使用。
Transcriptogram profiling is a method to present and analyze transcription data in a genome-wide scale that reduces noise and facilitates biological interpretation. An ordered gene list is produced, such that the probability that the genes are functionally associated exponentially decays with their distance on the list. This list presents a biological logic, evinced by the selective enrichment of successive intervals with Gene Ontology terms or KEGG pathways. Transcriptograms are expression profiles obtained by taking the average of gene expression over neighboring genes on this list. Transcriptograms enhance reproducibility and precision for expression measurements of functionally correlated gene sets. Here we present an ordering list for Homo sapiens and apply the transcriptogram profiling method to different datasets. We show that this method enhances experiment reproducibility and enhances signal. We applied the method to a diabetes study by Hwang and collaborators, which focused on expression differences between cybrids produced by the hybridization of mitochondria of diabetes mellitus donors with osteosarcoma cell lines, depleted of mitochondria. We found that the transcriptogram method revealed significant differential expression in gene sets linked to blood coagulation and wound healing pathways, and also to gene sets that do not represent any metabolic pathway or Gene Ontology term. These gene sets are connected to ECM-receptor interaction and secreted proteins. The transcriptogram profiling method provided an automatic way to define sets of genes with correlated expression, reduce noise in genome-wide transcription profiles, and enhance measure reproducibility and sensitivity. These advantages enabled biologic interpretation and pointed to differentially expressed gene sets in diabetes mellitus which were not previously defined. The online version of this article (doi:10.1186/1471-2164-15-1181) contains supplementary material, which is available to authorized users.
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