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

BMC Genomics

Rita MC de Almeida¹  João M Dinis²  Gabriel C Perrone²  Samoel RM da Silva² 

[1] Instituto Nacional de Ciência e Tecnologia: Sistemas Complexos, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, 91501-970 Porto Alegre, RS, Brazil;Instituto de Física, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, 91501-970 Porto Alegre, RS, Brazil

关键词: Microarray;    Transcriptome;    Gene expression analysis;    Transcriptogram;   

Others  :  1118424
DOI  :  10.1186/1471-2164-15-1181

 received in 2014-03-07, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

Background

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.

Results

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.

Conclusion

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.

【 授权许可】

   
2014 da Silva et al.; licensee BioMed Central.

【 图 表 】

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