Prediction of key gene function in spinal muscular atrophy using guilt by association method based on network and gene ontology.

Abstract

Guilt by association (GBA) algorithm has been widely used to predict gene functions statistically, and a network-based approach may increase the confidence and veracity of identifying molecular signatures for diseases. The aim of the present study was to suggest a gene ontology (GO)-based method by integrating the GBA algorithm and network, to identify key gene functions for spinal muscular atrophy (SMA). The inference of predicting key gene functions was comprised of four steps, preparing gene lists and sets; extracting differentially expressed genes (DEGs) using microarray data [linear models for microarray data (limma)] package; constructing a co-expression matrix on gene lists using the Spearman correlation coefficient method; and predicting gene functions by GBA algorithm. Ultimately, key gene functions were predicted according to the area under the curve (AUC) index for GO terms and the GO terms with AUC >0.7 were determined as the optimal gene functions for SMA. A total of 484 DEGs and 466 background GO terms were regarded as gene lists and sets for the subsequent analyses, respectively. The predicted results obtained from the network-based GBA approach showed 141 gene sets had a good classified performance with AUC >0.5. Most significantly, 3 gene sets with AUC >0.7 were denoted as seed gene functions for SMA, including cell morphogenesis, which is involved in differentiation and ossification. In conclusion, we have predicted 3 key gene functions for SMA compared with control utilizing network-based GBA algorithm. The findings may provide great insights to reveal pathological and molecular mechanism underlying SMA.