Diagnosing phenotypes of single-sample individuals by edge biomarkers.
Network or edge biomarkers are a reliable form to characterize phenotypes or diseases. However, obtaining edges or correlations between molecules for an individual requires measurement of multiple samples of that individual, which are generally unavailable in clinical practice. Thus, it is strongly demanded to diagnose a disease by edge or network biomarkers in one-sample-for-one-individual context. Here, we developed a new computational framework, EdgeBiomarker, to integrate edge and node biomarkers to diagnose phenotype of each single test sample. By applying the method to datasets of lung and breast cancer, it reveals new marker genes/gene-pairs and related sub-networks for distinguishing earlier and advanced cancer stages. Our method shows advantages over traditional methods: (i) edge biomarkers extracted from non-differentially expressed genes achieve better cross-validation accuracy of diagnosis than molecule or node biomarkers from differentially expressed genes, suggesting that certain pathogenic information is only present at the level of network and under-estimated by traditional methods; (ii) edge biomarkers categorize patients into low/high survival rate in a more reliable manner; (iii) edge biomarkers are significantly enriched in relevant biological functions or pathways, implying that the association changes in a network, rather than expression changes in individual molecules, tend to be causally related to cancer development. The new framework of edge biomarkers paves the way for diagnosing diseases and analyzing their molecular mechanisms by edges or networks in one-sample-for-one-individual basis. This also provides a powerful tool for precision medicine or big-data medicine.
Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Wanwei
W
Zhang
Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Tao
T
Zeng
Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xiaoping
X
Liu
Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China lnchen@sibs.ac.cn.
Luonan
L
Chen
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D019295:Computational Biology; D042241:Early Diagnosis; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D009362:Neoplasm Metastasis; D010641:Phenotype; D016016:Proportional Hazards Models
D014408:Biomarkers, Tumor
big biological data; disease diagnosis; edge biomarker; edge feature; progressive stages