Gaining confidence in biological interpretation of the microarray data: the functional consistence of the significant GO categories.
BACKGROUND
In microarray studies, numerous tools are available for functional enrichment analysis based on GO categories. Most of these tools, due to their requirement of a prior threshold for designating genes as differentially expressed genes (DEGs), are categorized as threshold-dependent methods that often suffer from a major criticism on their changing results with different thresholds.


RESULTS
In the present article, by considering the inherent correlation structure of the GO categories, a continuous measure based on semantic similarity of GO categories is proposed to investigate the functional consistence (or stability) of threshold-dependent methods. The results from several datasets show when simply counting overlapping categories between two groups, the significant category groups selected under different DEG thresholds are seemingly very different. However, based on the semantic similarity measure proposed in this article, the results are rather functionally consistent for a wide range of DEG thresholds. Moreover, we find that the functional consistence of gene lists ranked by SAM metric behaves relatively robust against changing DEG thresholds.


BACKGROUND
Source code in R is available on request from the authors.
Yang
Da
D
Department of Bioinformatics, Bio-pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory, Harbin Medical University, Harbin 150086, China.
Li
Yanhui
Y
Xiao
Hui
H
Liu
Qing
Q
Zhang
Min
M
Zhu
Jing
J
Ma
Wencai
W
Yao
Chen
C
Wang
Jing
J
Wang
Dong
D
Guo
Zheng
Z
Yang
Baofeng
B
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000145:classification; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D016247:Information Storage and Retrieval; D009363:Neoplasm Proteins / Q000032:analysis* / Q000145:classification; D009369:Neoplasms / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins