A novel approach for correction of crosstalk effects in pathway analysis and its application in osteoporosis research

• Published in: Scientific reports Vol. 8; no. 1; pp. 668 - 9
• Main Authors: Zhou, Yu, Gao, Yunlong, Xu, Chao, Shen, Hui, Tian, Qing, Deng, Hong-Wen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.01.2018; Nature Publishing Group
• Subjects: 38; 38/61; 631/208/199; 692/699/2743/316/801; Bone Density; Bone mineral density; Bone turnover; Data processing; Female; Gene Expression Profiling - methods; Gene Regulatory Networks; Hip; Humanities and Social Sciences; Humans; MAP kinase; MAP Kinase Signaling System; Metabolic disorders; Middle Aged; Mitochondria; Mitochondria - genetics; Monocytes; multidisciplinary; Oligonucleotide Array Sequence Analysis - methods; Osteoclastogenesis; Osteoporosis; Osteoporosis - genetics; Peripheral blood; Science; Science (multidisciplinary); Signal transduction
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-19196-2

Osteoporosis is a prevalent bone metabolic disease and peripheral blood monocytes represent a major systemic cell type for bone metabolism. To identify the key dysfunctional pathways in osteoporosis, we performed pathway analyses on microarray data of monocytes from subjects with extremely high/low hip bone mineral density. We first performed a traditional pathway analysis for which different pathways were treated as independent. However, genes overlap among pathways will lead to “crosstalk” phenomenon, which may lead to false positive/negative results. Therefore, we applied correction techniques including a novel approach that considers the correlation among genes to adjust the crosstalk effects in the analysis. In traditional analysis, 10 pathways were found to be significantly associated with BMD variation. After correction for crosstalk effects, three of them remained significant. Moreover, the MAPK signaling pathway, which has been shown to be important for osteoclastogenesis, became significant only after the correction for crosstalk effects. We also identified a new module mainly consisting of genes present in mitochondria to be significant. In summary, we describe a novel method to correct the crosstalk effect in pathway analysis and found five key independent pathways involved in BMD regulation, which may provide a better understanding of biological functional networks in osteoporosis.